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Trial record 14 of 50 for:    "Essential Thrombocythemia" | "Anti-Infective Agents"

Fludarabine Phosphate and Total Body Irradiation Followed by a Donor Peripheral Stem Cell Transplant in Treating Patients With Myelodysplastic Syndromes or Myeloproliferative Disorders

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00397813
Recruitment Status : Active, not recruiting
First Posted : November 10, 2006
Results First Posted : October 24, 2018
Last Update Posted : May 23, 2019
Sponsor:
Collaborators:
National Cancer Institute (NCI)
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Brenda Sandmaier, Fred Hutchinson Cancer Research Center

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative
Chronic Myelomonocytic Leukemia
de Novo Myelodysplastic Syndrome
Essential Thrombocythemia
Myeloproliferative Neoplasm
Paroxysmal Nocturnal Hemoglobinuria
Polycythemia Vera
Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase
Primary Myelofibrosis
Refractory Anemia
Refractory Anemia With Excess Blasts
Refractory Anemia With Ring Sideroblasts
Refractory Cytopenia With Multilineage Dysplasia
Refractory Cytopenia With Multilineage Dysplasia and Ring Sideroblasts
Interventions Drug: Cyclosporine
Drug: Fludarabine Phosphate
Other: Laboratory Biomarker Analysis
Drug: Mycophenolate Mofetil
Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation
Procedure: Peripheral Blood Stem Cell Transplantation
Radiation: Total-Body Irradiation
Enrollment 77
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Arm A - Dose Level 1 Arm A - Dose Level 2 Arm A - Dose Level 3 Arm B - Dose Level 1 Arm B - Dose Level 2 Arm B - Dose Level 3
Hide Arm/Group Description

Arm A - patients with MPD or MDS-RA/RARS Dose Level 1 - 300 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Arm A - patients with MPD or MDS-RA/RARS Dose Level 2 - 400 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Arm A - patients with MPD or MDS-RA/RARS Dose Level 3 - 450 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Arm B - patients with MDS-RAEB or CMML Dose Level 1 - 300 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Arm B - patients with MDS-RAEB or CMML Dose Level 2 - 400 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Arm B - patients with MDS-RAEB or CMML Dose Level 3 - 450 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Period Title: Overall Study
Started 36 0 0 12 5 24
Completed 36 0 0 12 5 24
Not Completed 0 0 0 0 0 0
Arm/Group Title Arm A - Dose Level 1 Arm A - Dose Level 2 Arm A - Dose Level 3 Arm B - Dose Level 1 Arm B - Dose Level 2 Arm B - Dose Level 3 Total
Hide Arm/Group Description

Arm A - patients with MPD or MDS-RA/RARS Dose Level 1 - 300 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Arm A - patients with MPD or MDS-RA/RARS Dose Level 2 - 400 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Arm A - patients with MPD or MDS-RA/RARS Dose Level 3 - 450 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Arm B - patients with MDS-RAEB or CMML Dose Level 1 - 300 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Arm B - patients with MDS-RAEB or CMML Dose Level 2 - 400 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Arm B - patients with MDS-RAEB or CMML Dose Level 3 - 450 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Total of all reporting groups
Overall Number of Baseline Participants 36 0 0 12 5 24 77
Hide Baseline Analysis Population Description
No patients were enrolled on arms A2 and A3 because dose escalation was never triggered.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 36 participants 0 participants 0 participants 12 participants 5 participants 24 participants 77 participants
<=18 years
0
   0.0%
0 0
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
18
  50.0%
0 0
5
  41.7%
2
  40.0%
5
  20.8%
30
  39.0%
>=65 years
18
  50.0%
0 0
7
  58.3%
3
  60.0%
19
  79.2%
47
  61.0%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 36 participants 0 participants 0 participants 12 participants 5 participants 24 participants 77 participants
64.5
(37 to 72)
66.5
(58 to 72)
68
(61 to 69)
68.5
(53 to 74)
67
(37 to 74)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 36 participants 0 participants 0 participants 12 participants 5 participants 24 participants 77 participants
Female
10
  27.8%
7
  58.3%
2
  40.0%
5
  20.8%
24
  31.2%
Male
26
  72.2%
5
  41.7%
3
  60.0%
19
  79.2%
53
  68.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 36 participants 0 participants 0 participants 12 participants 5 participants 24 participants 77 participants
Hispanic or Latino
1
   2.8%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.3%
Not Hispanic or Latino
35
  97.2%
12
 100.0%
4
  80.0%
23
  95.8%
74
  96.1%
Unknown or Not Reported
0
   0.0%
0
   0.0%
1
  20.0%
1
   4.2%
2
   2.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 36 participants 0 participants 0 participants 12 participants 5 participants 24 participants 77 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
4
  16.7%
4
   5.2%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
35
  97.2%
12
 100.0%
4
  80.0%
19
  79.2%
70
  90.9%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
1
   4.2%
1
   1.3%
Unknown or Not Reported
1
   2.8%
0
   0.0%
1
  20.0%
0
   0.0%
2
   2.6%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 36 participants 0 participants 0 participants 12 participants 5 participants 24 participants 77 participants
36 12 5 24 77
1.Primary Outcome
Title Number of Patients With HCT Failure.
Hide Description HCT failure will be defined as graft rejection (defined as < 5% donor T-cell chimerism) or disease progression within 200 days of transplant.
Time Frame 200 days
Hide Outcome Measure Data
Hide Analysis Population Description
No patients were enrolled on arms A2 and A3 because dose escalation was never triggered.
Arm/Group Title Arm A - Dose Level 1 Arm A - Dose Level 2 Arm A - Dose Level 3 Arm B - Dose Level 1 Arm B - Dose Level 2 Arm B - Dose Level 3
Hide Arm/Group Description:

Arm A - patients with MPD or MDS-RA/RARS Dose Level 1 - 300 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Arm A - patients with MPD or MDS-RA/RARS Dose Level 2 - 400 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Arm A - patients with MPD or MDS-RA/RARS Dose Level 3 - 450 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Arm B - patients with MDS-RAEB or CMML Dose Level 1 - 300 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Arm B - patients with MDS-RAEB or CMML Dose Level 2 - 400 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Arm B - patients with MDS-RAEB or CMML Dose Level 3 - 450 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Overall Number of Participants Analyzed 36 0 0 12 5 24
Measure Type: Count of Participants
Unit of Measure: Participants
4
  11.1%
0 0
5
  41.7%
3
  60.0%
2
   8.3%
2.Secondary Outcome
Title Number of Patients Who Had Infections
Hide Description Number of patients who experienced bacterial, fungal, or viral infections.
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
No patients were enrolled on arms A2 and A3 because dose escalation was never triggered.
Arm/Group Title Arm A - Dose Level 1 Arm A - Dose Level 2 Arm A - Dose Level 3 Arm B - Dose Level 1 Arm B - Dose Level 2 Arm B - Dose Level 3
Hide Arm/Group Description:

Arm A - patients with MPD or MDS-RA/RARS Dose Level 1 - 300 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Arm A - patients with MPD or MDS-RA/RARS Dose Level 2 - 400 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Arm A - patients with MPD or MDS-RA/RARS Dose Level 3 - 450 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Arm B - patients with MDS-RAEB or CMML Dose Level 1 - 300 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Arm B - patients with MDS-RAEB or CMML Dose Level 2 - 400 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Arm B - patients with MDS-RAEB or CMML Dose Level 3 - 450 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Overall Number of Participants Analyzed 36 0 0 12 5 24
Measure Type: Count of Participants
Unit of Measure: Participants
24
  66.7%
0 0
12
 100.0%
4
  80.0%
24
 100.0%
3.Secondary Outcome
Title Number of Patients Who Engrafted
Hide Description Continued engraftment will be defined as the detection of donor T-cells (CD3+) as a proportion of the total T-cell of greater than 5%.
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
No patients were enrolled on arms A2 and A3 because dose escalation was never triggered.
Arm/Group Title Arm A - Dose Level 1 Arm A - Dose Level 2 Arm A - Dose Level 3 Arm B - Dose Level 1 Arm B - Dose Level 2 Arm B - Dose Level 3
Hide Arm/Group Description:

Arm A - patients with MPD or MDS-RA/RARS Dose Level 1 - 300 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Arm A - patients with MPD or MDS-RA/RARS Dose Level 2 - 400 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Arm A - patients with MPD or MDS-RA/RARS Dose Level 3 - 450 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Arm B - patients with MDS-RAEB or CMML Dose Level 1 - 300 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Arm B - patients with MDS-RAEB or CMML Dose Level 2 - 400 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Arm B - patients with MDS-RAEB or CMML Dose Level 3 - 450 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Overall Number of Participants Analyzed 36 0 0 12 5 24
Measure Type: Count of Participants
Unit of Measure: Participants
35
  97.2%
0 0
12
 100.0%
4
  80.0%
24
 100.0%
4.Secondary Outcome
Title Number of Patients With Progression-free Survival
Hide Description Evidence of disease progression will be an indication for therapeutic intervention. Defined as any evidence by morphologic or flow cytometric evaluation of the bone marrow aspirate of an incremental increase in 5% blasts in MDS/CMML; defined as any evidence of blastic transformation in agnogenic myeloid metaplasia/atypical CML; and defined as progressive erythrocytosis, thrombocytosis, or evidence of leukemic transformation in polycythemia vera and essential thrombocythemia.
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
No patients were enrolled on arms A2 and A3 because dose escalation was never triggered.
Arm/Group Title Arm A - Dose Level 1 Arm A - Dose Level 2 Arm A - Dose Level 3 Arm B - Dose Level 1 Arm B - Dose Level 2 Arm B - Dose Level 3
Hide Arm/Group Description:

Arm A - patients with MPD or MDS-RA/RARS Dose Level 1 - 300 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Arm A - patients with MPD or MDS-RA/RARS Dose Level 2 - 400 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Arm A - patients with MPD or MDS-RA/RARS Dose Level 3 - 450 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Arm B - patients with MDS-RAEB or CMML Dose Level 1 - 300 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Arm B - patients with MDS-RAEB or CMML Dose Level 2 - 400 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Arm B - patients with MDS-RAEB or CMML Dose Level 3 - 450 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Overall Number of Participants Analyzed 36 0 0 12 5 24
Measure Type: Count of Participants
Unit of Measure: Participants
24
  66.7%
0 0
1
   8.3%
2
  40.0%
11
  45.8%
5.Secondary Outcome
Title Number of Patients With Relapse/Progression
Hide Description Evidence of disease progression will be an indication for therapeutic intervention. Defined as any evidence by morphologic or flow cytometric evaluation of the bone marrow aspirate of an incremental increase in 5% blasts in MDS/CMML; defined as any evidence of blastic transformation in agnogenic myeloid metaplasia/atypical CML; and defined as progressive erythrocytosis, thrombocytosis, or evidence of leukemic transformation in polycythemia vera and essential thrombocythemia.
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
No patients were enrolled on arms A2 and A3 because dose escalation was never triggered.
Arm/Group Title Arm A - Dose Level 1 Arm A - Dose Level 2 Arm A - Dose Level 3 Arm B - Dose Level 1 Arm B - Dose Level 2 Arm B - Dose Level 3
Hide Arm/Group Description:

Arm A - patients with MPD or MDS-RA/RARS Dose Level 1 - 300 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Arm A - patients with MPD or MDS-RA/RARS Dose Level 2 - 400 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Arm A - patients with MPD or MDS-RA/RARS Dose Level 3 - 450 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Arm B - patients with MDS-RAEB or CMML Dose Level 1 - 300 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Arm B - patients with MDS-RAEB or CMML Dose Level 2 - 400 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Arm B - patients with MDS-RAEB or CMML Dose Level 3 - 450 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Overall Number of Participants Analyzed 36 0 0 12 5 24
Measure Type: Count of Participants
Unit of Measure: Participants
6
  16.7%
0 0
6
  50.0%
3
  60.0%
6
  25.0%
Time Frame AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
Adverse Event Reporting Description No patients were enrolled on arms A2 and A3 because dose escalation was never triggered.
 
Arm/Group Title Arm A - Dose Level 1 Arm A - Dose Level 2 Arm A - Dose Level 3 Arm B - Dose Level 1 Arm B - Dose Level 2 Arm B - Dose Level 3
Hide Arm/Group Description

Arm A - patients with MPD or MDS-RA/RARS Dose Level 1 - 300 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Arm A - patients with MPD or MDS-RA/RARS Dose Level 2 - 400 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Arm A - patients with MPD or MDS-RA/RARS Dose Level 3 - 450 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Arm B - patients with MDS-RAEB or CMML Dose Level 1 - 300 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Arm B - patients with MDS-RAEB or CMML Dose Level 2 - 400 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

Arm B - patients with MDS-RAEB or CMML Dose Level 3 - 450 cGy TBI

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

All-Cause Mortality
Arm A - Dose Level 1 Arm A - Dose Level 2 Arm A - Dose Level 3 Arm B - Dose Level 1 Arm B - Dose Level 2 Arm B - Dose Level 3
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   10/36 (27.78%)      0/0      0/0      10/12 (83.33%)      3/5 (60.00%)      9/24 (37.50%)    
Show Serious Adverse Events Hide Serious Adverse Events
Arm A - Dose Level 1 Arm A - Dose Level 2 Arm A - Dose Level 3 Arm B - Dose Level 1 Arm B - Dose Level 2 Arm B - Dose Level 3
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/36 (8.33%)      0/0      0/0      7/12 (58.33%)      2/5 (40.00%)      4/24 (16.67%)    
Blood and lymphatic system disorders             
Febrile neutropenia   0/36 (0.00%)  0 0/0  0 0/0  0 0/12 (0.00%)  0 1/5 (20.00%)  1 0/24 (0.00%)  0
Gastrointestinal disorders             
Abdominal pain   0/36 (0.00%)  0 0/0  0 0/0  0 1/12 (8.33%)  1 0/5 (0.00%)  0 0/24 (0.00%)  0
General disorders             
Multi-organ failure   0/36 (0.00%)  0 0/0  0 0/0  0 2/12 (16.67%)  2 0/5 (0.00%)  0 1/24 (4.17%)  2
Immune system disorders             
GVHD   1/36 (2.78%)  1 0/0  0 0/0  0 1/12 (8.33%)  1 0/5 (0.00%)  0 1/24 (4.17%)  1
Infections and infestations             
Lung infection   0/36 (0.00%)  0 0/0  0 0/0  0 1/12 (8.33%)  1 1/5 (20.00%)  1 0/24 (0.00%)  0
Mucosal infection   0/36 (0.00%)  0 0/0  0 0/0  0 1/12 (8.33%)  1 0/5 (0.00%)  0 0/24 (0.00%)  0
Investigations             
Blood bilirubin increased   1/36 (2.78%)  1 0/0  0 0/0  0 0/12 (0.00%)  0 0/5 (0.00%)  0 1/24 (4.17%)  1
Nervous system disorders             
Seizure   0/36 (0.00%)  0 0/0  0 0/0  0 0/12 (0.00%)  0 0/5 (0.00%)  0 1/24 (4.17%)  1
Psychiatric disorders             
Psychiatric disorders - Other, specify (altered mental status)   0/36 (0.00%)  0 0/0  0 0/0  0 1/12 (8.33%)  1 0/5 (0.00%)  0 0/24 (0.00%)  0
Suicide attempt   1/36 (2.78%)  1 0/0  0 0/0  0 0/12 (0.00%)  0 0/5 (0.00%)  0 0/24 (0.00%)  0
Respiratory, thoracic and mediastinal disorders             
Hypoxia   0/36 (0.00%)  0 0/0  0 0/0  0 1/12 (8.33%)  1 0/5 (0.00%)  0 0/24 (0.00%)  0
Respiratory Failure   1/36 (2.78%)  1 0/0  0 0/0  0 1/12 (8.33%)  1 0/5 (0.00%)  0 1/24 (4.17%)  1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Arm A - Dose Level 1 Arm A - Dose Level 2 Arm A - Dose Level 3 Arm B - Dose Level 1 Arm B - Dose Level 2 Arm B - Dose Level 3
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   16/36 (44.44%)      0/0      0/0      9/12 (75.00%)      2/5 (40.00%)      13/24 (54.17%)    
Blood and lymphatic system disorders             
Anemia   0/36 (0.00%)  0 0/0  0 0/0  0 1/12 (8.33%)  1 0/5 (0.00%)  0 0/24 (0.00%)  0
Febrile neutropenia   0/36 (0.00%)  0 0/0  0 0/0  0 4/12 (33.33%)  4 0/5 (0.00%)  0 5/24 (20.83%)  5
Hemolysis   1/36 (2.78%)  1 0/0  0 0/0  0 0/12 (0.00%)  0 0/5 (0.00%)  0 0/24 (0.00%)  0
Hemolytic uremic syndrome   0/36 (0.00%)  0 0/0  0 0/0  0 0/12 (0.00%)  0 0/5 (0.00%)  0 1/24 (4.17%)  1
Cardiac disorders             
Atrial fibrillation   0/36 (0.00%)  0 0/0  0 0/0  0 0/12 (0.00%)  0 0/5 (0.00%)  0 1/24 (4.17%)  1
Atrial flutter   0/36 (0.00%)  0 0/0  0 0/0  0 1/12 (8.33%)  1 0/5 (0.00%)  0 1/24 (4.17%)  1
Heart failure   0/36 (0.00%)  0 0/0  0 0/0  0 1/12 (8.33%)  1 1/5 (20.00%)  1 1/24 (4.17%)  1
Myocardial infarction   0/36 (0.00%)  0 0/0  0 0/0  0 0/12 (0.00%)  0 0/5 (0.00%)  0 1/24 (4.17%)  1
Pericardial effusion   1/36 (2.78%)  1 0/0  0 0/0  0 0/12 (0.00%)  0 0/5 (0.00%)  0 0/24 (0.00%)  0
Supraventricular tachycardia   0/36 (0.00%)  0 0/0  0 0/0  0 0/12 (0.00%)  0 1/5 (20.00%)  1 0/24 (0.00%)  0
Gastrointestinal disorders             
Abdominal pain   0/36 (0.00%)  0 0/0  0 0/0  0 1/12 (8.33%)  1 0/5 (0.00%)  0 0/24 (0.00%)  0
Ascites   0/36 (0.00%)  0 0/0  0 0/0  0 0/12 (0.00%)  0 0/5 (0.00%)  0 1/24 (4.17%)  1
Diarrhea   2/36 (5.56%)  2 0/0  0 0/0  0 0/12 (0.00%)  0 0/5 (0.00%)  0 1/24 (4.17%)  1
Esophagitis   0/36 (0.00%)  0 0/0  0 0/0  0 1/12 (8.33%)  1 0/5 (0.00%)  0 0/24 (0.00%)  0
Gastric hemorrhage   1/36 (2.78%)  1 0/0  0 0/0  0 0/12 (0.00%)  0 0/5 (0.00%)  0 1/24 (4.17%)  1
Gastritis   0/36 (0.00%)  0 0/0  0 0/0  0 0/12 (0.00%)  0 0/5 (0.00%)  0 1/24 (4.17%)  1
Mucositis oral   0/36 (0.00%)  0 0/0  0 0/0  0 0/12 (0.00%)  0 0/5 (0.00%)  0 1/24 (4.17%)  1
General disorders             
Flu like symptoms   1/36 (2.78%)  2 0/0  0 0/0  0 0/12 (0.00%)  0 0/5 (0.00%)  0 0/24 (0.00%)  0
Infections and infestations             
Sepsis   0/36 (0.00%)  0 0/0  0 0/0  0 0/12 (0.00%)  0 0/5 (0.00%)  0 1/24 (4.17%)  1
Investigations             
Blood antidiuretic hormone abnormal   0/36 (0.00%)  0 0/0  0 0/0  0 1/12 (8.33%)  1 0/5 (0.00%)  0 0/24 (0.00%)  0
Blood bilirubin increased   9/36 (25.00%)  11 0/0  0 0/0  0 3/12 (25.00%)  3 2/5 (40.00%)  2 6/24 (25.00%)  6
Carbon monoxide diffusing capacity decreased   1/36 (2.78%)  1 0/0  0 0/0  0 0/12 (0.00%)  0 0/5 (0.00%)  0 0/24 (0.00%)  0
Nervous system disorders             
Syncope   0/36 (0.00%)  0 0/0  0 0/0  0 0/12 (0.00%)  0 0/5 (0.00%)  0 1/24 (4.17%)  1
Renal and urinary disorders             
Acute kidney injury   1/36 (2.78%)  1 0/0  0 0/0  0 1/12 (8.33%)  1 0/5 (0.00%)  0 2/24 (8.33%)  2
Respiratory, thoracic and mediastinal disorders             
Adult respiratory distress syndrome   1/36 (2.78%)  1 0/0  0 0/0  0 0/12 (0.00%)  0 0/5 (0.00%)  0 2/24 (8.33%)  2
Hypoxia   4/36 (11.11%)  6 0/0  0 0/0  0 3/12 (25.00%)  3 2/5 (40.00%)  2 5/24 (20.83%)  5
Pleural effusion   0/36 (0.00%)  0 0/0  0 0/0  0 1/12 (8.33%)  1 0/5 (0.00%)  0 0/24 (0.00%)  0
Respiratory failure   0/36 (0.00%)  0 0/0  0 0/0  0 0/12 (0.00%)  0 0/5 (0.00%)  0 1/24 (4.17%)  1
Skin and subcutaneous tissue disorders             
Rash maculo-papular   0/36 (0.00%)  0 0/0  0 0/0  0 0/12 (0.00%)  0 0/5 (0.00%)  0 1/24 (4.17%)  1
Vascular disorders             
Hypotension   1/36 (2.78%)  1 0/0  0 0/0  0 2/12 (16.67%)  2 0/5 (0.00%)  0 2/24 (8.33%)  2
Thromboembolic event   1/36 (2.78%)  1 0/0  0 0/0  0 1/12 (8.33%)  1 0/5 (0.00%)  0 3/24 (12.50%)  3
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Brenda M. Sandmaier
Organization: Fred Hutchinson Cancer Research Center
Phone: (206) 667-4961
EMail: bsandmai@fredhutch.org
Layout table for additonal information
Responsible Party: Brenda Sandmaier, Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT00397813     History of Changes
Other Study ID Numbers: 2056.00
NCI-2010-00237 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2056.00 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
P01CA018029 ( U.S. NIH Grant/Contract )
P30CA015704 ( U.S. NIH Grant/Contract )
First Submitted: November 9, 2006
First Posted: November 10, 2006
Results First Submitted: September 25, 2018
Results First Posted: October 24, 2018
Last Update Posted: May 23, 2019