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Fludarabine Phosphate, Cyclophosphamide, Total-Body Irradiation, and Donor Bone Marrow Transplant Followed by Donor Natural Killer Cell Therapy, Mycophenolate Mofetil, and Tacrolimus in Treating Patients With Hematologic Cancer

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ClinicalTrials.gov Identifier: NCT00789776
Recruitment Status : Active, not recruiting
First Posted : November 13, 2008
Results First Posted : July 12, 2018
Last Update Posted : July 12, 2018
Sponsor:
Collaborators:
National Cancer Institute (NCI)
The Wayne D. Kuni and Joan E. Kuni Foundation
Information provided by (Responsible Party):
Brenda Sandmaier, Fred Hutchinson Cancer Research Center

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Acute Lymphoblastic Leukemia
Acute Myeloid Leukemia
Aggressive Non-Hodgkin Lymphoma
Diffuse Large B-Cell Lymphoma
Previously Treated Myelodysplastic Syndrome
Recurrent Chronic Lymphocytic Leukemia
Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive
Recurrent Indolent Adult Non-Hodgkin Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Plasma Cell Myeloma
Recurrent Small Lymphocytic Lymphoma
Refractory Chronic Lymphocytic Leukemia
Refractory Hodgkin Lymphoma
Refractory Plasma Cell Myeloma
Refractory Small Lymphocytic Lymphoma
Waldenstrom Macroglobulinemia
Interventions Procedure: Allogeneic Bone Marrow Transplantation
Drug: Cyclophosphamide
Drug: Fludarabine Phosphate
Other: Laboratory Biomarker Analysis
Drug: Mycophenolate Mofetil
Biological: Natural Killer Cell Therapy
Drug: Tacrolimus
Radiation: Total-Body Irradiation
Enrollment 41

Recruitment Details  
Pre-assignment Details  
Arm/Group Title Dose 1 (2.5 x 10^6/kg NK Cells) Dose 2 (5.0 x 10^6/kg NK Cells)
Hide Arm/Group Description

CONDITIONING: Patients receive fludarabine IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1 hour on days -6 and -5. Patients undergo total-body irradiation on day -1.

DONOR BONE MARROW TRANSPLANTATION: Patients undergo donor bone marrow transplantation on day 0.

POST-TRANSPLANTATION IMMUNOSUPPRESSION: Patients receive cyclophosphamide IV over 1 hour on day 3 and mycophenolate mofetil PO TID on days 4 - 40, followed by a taper until day 84 in the absence of GVHD. Patients also receive tacrolimus IV continuously or IV QD over 1-2 hours or PO BID on days 4 - 84, followed by a taper until day 180 in the absence of GVHD.

NK CELL INFUSION: Patients undergo donor lymphocyte infusion of 2.5 x 10^6/kg NK cells on day 7.

Allogeneic Bone Marrow Transplantation: Undergo donor bone marrow transplantation

Laboratory Biomarker Analysis: Correlative studies

CONDITIONING: Patients receive fludarabine IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1 hour on days -6 and -5. Patients undergo total-body irradiation on day -1.

DONOR BONE MARROW TRANSPLANTATION: Patients undergo donor bone marrow transplantation on day 0.

POST-TRANSPLANTATION IMMUNOSUPPRESSION: Patients receive cyclophosphamide IV over 1 hour on day 3 and mycophenolate mofetil PO TID on days 4 - 40, followed by a taper until day 84 in the absence of GVHD. Patients also receive tacrolimus IV continuously or IV QD over 1-2 hours or PO BID on days 4 - 84, followed by a taper until day 180 in the absence of GVHD.

NK CELL INFUSION: Patients undergo donor lymphocyte infusion of 5.0 x 10^6/kg NK cells on day 7.

Allogeneic Bone Marrow Transplantation: Undergo donor bone marrow transplantation

Laboratory Biomarker Analysis: Correlative studies

Period Title: Overall Study
Started 5 36
Completed 5 35
Not Completed 0 1
Arm/Group Title Dose 1 (2.5 x 10^6/kg NK Cells) Dose 2 (5.0 x 10^6/kg NK Cells) Total
Hide Arm/Group Description

CONDITIONING: Patients receive fludarabine IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1 hour on days -6 and -5. Patients undergo total-body irradiation on day -1.

DONOR BONE MARROW TRANSPLANTATION: Patients undergo donor bone marrow transplantation on day 0.

POST-TRANSPLANTATION IMMUNOSUPPRESSION: Patients receive cyclophosphamide IV over 1 hour on day 3 and mycophenolate mofetil PO TID on days 4 - 40, followed by a taper until day 84 in the absence of GVHD. Patients also receive tacrolimus IV continuously or IV QD over 1-2 hours or PO BID on days 4 - 84, followed by a taper until day 180 in the absence of GVHD.

NK CELL INFUSION: Patients undergo donor lymphocyte infusion of 2.5 x 10^6/kg NK cells on day 7.

Allogeneic Bone Marrow Transplantation: Undergo donor bone marrow transplantation

Laboratory Biomarker Analysis: Correlative studies

CONDITIONING: Patients receive fludarabine IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1 hour on days -6 and -5. Patients undergo total-body irradiation on day -1.

DONOR BONE MARROW TRANSPLANTATION: Patients undergo donor bone marrow transplantation on day 0.

POST-TRANSPLANTATION IMMUNOSUPPRESSION: Patients receive cyclophosphamide IV over 1 hour on day 3 and mycophenolate mofetil PO TID on days 4 - 40, followed by a taper until day 84 in the absence of GVHD. Patients also receive tacrolimus IV continuously or IV QD over 1-2 hours or PO BID on days 4 - 84, followed by a taper until day 180 in the absence of GVHD.

NK CELL INFUSION: Patients undergo donor lymphocyte infusion of 5.0 x 10^6/kg NK cells on day 7.

Allogeneic Bone Marrow Transplantation: Undergo donor bone marrow transplantation

Laboratory Biomarker Analysis: Correlative studies

Total of all reporting groups
Overall Number of Baseline Participants 5 36 41
Hide Baseline Analysis Population Description
One subject aborted transplant after conditioning due to donor ineligibility. This subject was counted towards accrual but not evaluated with respect to outcome measures.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 36 participants 41 participants
<=18 years
1
  20.0%
10
  27.8%
11
  26.8%
Between 18 and 65 years
4
  80.0%
23
  63.9%
27
  65.9%
>=65 years
0
   0.0%
3
   8.3%
3
   7.3%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 5 participants 36 participants 41 participants
22.2
(14.5 to 43.7)
55.65
(8.1 to 75.2)
47.6
(8.1 to 75.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 36 participants 41 participants
Female
2
  40.0%
11
  30.6%
13
  31.7%
Male
3
  60.0%
25
  69.4%
28
  68.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 36 participants 41 participants
Hispanic or Latino
1
  20.0%
5
  13.9%
6
  14.6%
Not Hispanic or Latino
4
  80.0%
31
  86.1%
35
  85.4%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 36 participants 41 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
  20.0%
1
   2.8%
2
   4.9%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
6
  16.7%
6
  14.6%
White
4
  80.0%
28
  77.8%
32
  78.0%
More than one race
0
   0.0%
1
   2.8%
1
   2.4%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 5 participants 36 participants 41 participants
5
 100.0%
36
 100.0%
41
 100.0%
1.Primary Outcome
Title Number of Participants With Dose Limiting Toxicities
Hide Description Defined as having at least one of the following adverse events, independent of the attribution to the Natural Killer cell infusion: grade IV infusional toxicity (based on the Adapted Common Toxicity Criteria); grade IV regimen-related toxicity (based on Adapted Common Toxicity Criteria); grade IV acute Graft-Versus-Host Disease; non-relapse mortality.
Time Frame Day 35 (28 days after NK cell infusion)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
One subject aborted transplant after conditioning due to donor ineligibility. This subject was counted towards accrual but not evaluated with respect to outcome measures.
Arm/Group Title Dose 1 (2.5 x 10^6/kg NK Cells) Dose 2 (5.0 x 10^6/kg NK Cells)
Hide Arm/Group Description:

CONDITIONING: Patients receive fludarabine IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1 hour on days -6 and -5. Patients undergo total-body irradiation on day -1.

DONOR BONE MARROW TRANSPLANTATION: Patients undergo donor bone marrow transplantation on day 0.

POST-TRANSPLANTATION IMMUNOSUPPRESSION: Patients receive cyclophosphamide IV over 1 hour on day 3 and mycophenolate mofetil PO TID on days 4 - 40, followed by a taper until day 84 in the absence of GVHD. Patients also receive tacrolimus IV continuously or IV QD over 1-2 hours or PO BID on days 4 - 84, followed by a taper until day 180 in the absence of GVHD.

NK CELL INFUSION: Patients undergo donor lymphocyte infusion of 2.5 x 10^6/kg NK cells on day 7.

Allogeneic Bone Marrow Transplantation: Undergo donor bone marrow transplantation

Laboratory Biomarker Analysis: Correlative studies

CONDITIONING: Patients receive fludarabine IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1 hour on days -6 and -5. Patients undergo total-body irradiation on day -1.

DONOR BONE MARROW TRANSPLANTATION: Patients undergo donor bone marrow transplantation on day 0.

POST-TRANSPLANTATION IMMUNOSUPPRESSION: Patients receive cyclophosphamide IV over 1 hour on day 3 and mycophenolate mofetil PO TID on days 4 - 40, followed by a taper until day 84 in the absence of GVHD. Patients also receive tacrolimus IV continuously or IV QD over 1-2 hours or PO BID on days 4 - 84, followed by a taper until day 180 in the absence of GVHD.

NK CELL INFUSION: Patients undergo donor lymphocyte infusion of 5.0 x 10^6/kg NK cells on day 7.

Allogeneic Bone Marrow Transplantation: Undergo donor bone marrow transplantation

Laboratory Biomarker Analysis: Correlative studies

Overall Number of Participants Analyzed 5 35
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
2.Primary Outcome
Title Number of Participants With Relapsed Disease
Hide Description

CML New cytogenetic abnormality and/or development of accelerated phase or blast crisis. The criteria for accelerated phase will be defined as unexplained fever greater than 38.3°C, new clonal cytogenetic abnormalities in addition to a single Ph-positive chromosome, marrow blasts and promyelocytes >20%.

AML, ALL >5% marrow blasts by morphologic or flow cytometric, or appearance of extramedullary disease.

CLL ≥1 of: Physical exam/Imaging studies (nodes, liver, and/or spleen) ≥50% increase or new, circulating lymphocytes by morphology and/or flow cytometry ≥50% increase, and lymph node biopsy w/ Richter's transformation.

NHL >25% increase in the sum of the products of the perpendicular diameters of marker lesions, or the appearance of new lesions.

MM

≥100% increase of the serum myeloma protein from its lowest level, or reappearance of myeloma peaks that had disappeared w/ treatment; or definite increase in the size or number of plasmacytomas or lytic bone lesions.

Time Frame At 1 year
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
One subject aborted transplant after conditioning due to donor ineligibility. This subject was counted towards accrual but not evaluated with respect to outcome measures.
Arm/Group Title Dose 1 (2.5 x 10^6/kg NK Cells) Dose 2 (5.0 x 10^6/kg NK Cells)
Hide Arm/Group Description:

CONDITIONING: Patients receive fludarabine IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1 hour on days -6 and -5. Patients undergo total-body irradiation on day -1.

DONOR BONE MARROW TRANSPLANTATION: Patients undergo donor bone marrow transplantation on day 0.

POST-TRANSPLANTATION IMMUNOSUPPRESSION: Patients receive cyclophosphamide IV over 1 hour on day 3 and mycophenolate mofetil PO TID on days 4 - 40, followed by a taper until day 84 in the absence of GVHD. Patients also receive tacrolimus IV continuously or IV QD over 1-2 hours or PO BID on days 4 - 84, followed by a taper until day 180 in the absence of GVHD.

NK CELL INFUSION: Patients undergo donor lymphocyte infusion of 2.5 x 10^6/kg NK cells on day 7.

Allogeneic Bone Marrow Transplantation: Undergo donor bone marrow transplantation

Laboratory Biomarker Analysis: Correlative studies

CONDITIONING: Patients receive fludarabine IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1 hour on days -6 and -5. Patients undergo total-body irradiation on day -1.

DONOR BONE MARROW TRANSPLANTATION: Patients undergo donor bone marrow transplantation on day 0.

POST-TRANSPLANTATION IMMUNOSUPPRESSION: Patients receive cyclophosphamide IV over 1 hour on day 3 and mycophenolate mofetil PO TID on days 4 - 40, followed by a taper until day 84 in the absence of GVHD. Patients also receive tacrolimus IV continuously or IV QD over 1-2 hours or PO BID on days 4 - 84, followed by a taper until day 180 in the absence of GVHD.

NK CELL INFUSION: Patients undergo donor lymphocyte infusion of 5.0 x 10^6/kg NK cells on day 7.

Allogeneic Bone Marrow Transplantation: Undergo donor bone marrow transplantation

Laboratory Biomarker Analysis: Correlative studies

Overall Number of Participants Analyzed 5 35
Measure Type: Count of Participants
Unit of Measure: Participants
1
  20.0%
10
  28.6%
3.Primary Outcome
Title Number of Participants With Grades III-IV Acute GVHD
Hide Description

Number of patients who developed acute GVHD post-transplant. aGVHD Stages

Skin:

a maculopapular eruption involving < 25% BSA a maculopapular eruption involving 25 - 50% BSA generalized erythroderma generalized erythroderma with bullous formation and often with desquamation

Liver:

bilirubin 2.0 - 3.0 mg/100 mL bilirubin 3 - 5.9 mg/100 mL bilirubin 6 - 14.9 mg/100 mL bilirubin > 15 mg/100 mL

Gut:

Diarrhea is graded 1 - 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as 1 in severity. The severity of gut involvement is assigned to the most severe involvement noted. Patients with visible bloody diarrhea are at least stage 2 gut and grade 3 overall.

aGVHD Grades Grade III: Stage 2 - 4 gut involvement and/or stage 2 - 4 liver involvement Grade IV: Pattern and severity of GVHD similar to grade 3 with extreme constitutional symptoms or death

Time Frame Day 100
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
One subject aborted transplant after conditioning due to donor ineligibility. This subject was counted towards accrual but not evaluated with respect to outcome measures.
Arm/Group Title Dose 1 (2.5 x 10^6/kg NK Cells) Dose 2 (5.0 x 10^6/kg NK Cells)
Hide Arm/Group Description:

CONDITIONING: Patients receive fludarabine IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1 hour on days -6 and -5. Patients undergo total-body irradiation on day -1.

DONOR BONE MARROW TRANSPLANTATION: Patients undergo donor bone marrow transplantation on day 0.

POST-TRANSPLANTATION IMMUNOSUPPRESSION: Patients receive cyclophosphamide IV over 1 hour on day 3 and mycophenolate mofetil PO TID on days 4 - 40, followed by a taper until day 84 in the absence of GVHD. Patients also receive tacrolimus IV continuously or IV QD over 1-2 hours or PO BID on days 4 - 84, followed by a taper until day 180 in the absence of GVHD.

NK CELL INFUSION: Patients undergo donor lymphocyte infusion of 2.5 x 10^6/kg NK cells on day 7.

Allogeneic Bone Marrow Transplantation: Undergo donor bone marrow transplantation

Laboratory Biomarker Analysis: Correlative studies

CONDITIONING: Patients receive fludarabine IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1 hour on days -6 and -5. Patients undergo total-body irradiation on day -1.

DONOR BONE MARROW TRANSPLANTATION: Patients undergo donor bone marrow transplantation on day 0.

POST-TRANSPLANTATION IMMUNOSUPPRESSION: Patients receive cyclophosphamide IV over 1 hour on day 3 and mycophenolate mofetil PO TID on days 4 - 40, followed by a taper until day 84 in the absence of GVHD. Patients also receive tacrolimus IV continuously or IV QD over 1-2 hours or PO BID on days 4 - 84, followed by a taper until day 180 in the absence of GVHD.

NK CELL INFUSION: Patients undergo donor lymphocyte infusion of 5.0 x 10^6/kg NK cells on day 7.

Allogeneic Bone Marrow Transplantation: Undergo donor bone marrow transplantation

Laboratory Biomarker Analysis: Correlative studies

Overall Number of Participants Analyzed 5 35
Measure Type: Count of Participants
Unit of Measure: Participants
1
  20.0%
0
   0.0%
4.Primary Outcome
Title Number of Non-relapse Participant Mortalities
Hide Description Defined as death in any patient for whom there has not been a diagnosis of relapse or disease progression.
Time Frame Day 200
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
One subject aborted transplant after conditioning due to donor ineligibility. This subject was counted towards accrual but not evaluated with respect to outcome measures.
Arm/Group Title Dose 1 (2.5 x 10^6/kg NK Cells) Dose 2 (5.0 x 10^6/kg NK Cells)
Hide Arm/Group Description:

CONDITIONING: Patients receive fludarabine IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1 hour on days -6 and -5. Patients undergo total-body irradiation on day -1.

DONOR BONE MARROW TRANSPLANTATION: Patients undergo donor bone marrow transplantation on day 0.

POST-TRANSPLANTATION IMMUNOSUPPRESSION: Patients receive cyclophosphamide IV over 1 hour on day 3 and mycophenolate mofetil PO TID on days 4 - 40, followed by a taper until day 84 in the absence of GVHD. Patients also receive tacrolimus IV continuously or IV QD over 1-2 hours or PO BID on days 4 - 84, followed by a taper until day 180 in the absence of GVHD.

NK CELL INFUSION: Patients undergo donor lymphocyte infusion of 2.5 x 10^6/kg NK cells on day 7.

Allogeneic Bone Marrow Transplantation: Undergo donor bone marrow transplantation

Laboratory Biomarker Analysis: Correlative studies

CONDITIONING: Patients receive fludarabine IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1 hour on days -6 and -5. Patients undergo total-body irradiation on day -1.

DONOR BONE MARROW TRANSPLANTATION: Patients undergo donor bone marrow transplantation on day 0.

POST-TRANSPLANTATION IMMUNOSUPPRESSION: Patients receive cyclophosphamide IV over 1 hour on day 3 and mycophenolate mofetil PO TID on days 4 - 40, followed by a taper until day 84 in the absence of GVHD. Patients also receive tacrolimus IV continuously or IV QD over 1-2 hours or PO BID on days 4 - 84, followed by a taper until day 180 in the absence of GVHD.

NK CELL INFUSION: Patients undergo donor lymphocyte infusion of 5.0 x 10^6/kg NK cells on day 7.

Allogeneic Bone Marrow Transplantation: Undergo donor bone marrow transplantation

Laboratory Biomarker Analysis: Correlative studies

Overall Number of Participants Analyzed 5 35
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
5.Primary Outcome
Title Number of Participants Who Experienced Graft Failure
Hide Description Graft failure is defined as grade IV thrombocytopenia and neutropenia after Day +21 that lasts >2 weeks and is refractory to growth factor support.
Time Frame Day 100
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
One subject aborted transplant after conditioning due to donor ineligibility. This subject was counted towards accrual but not evaluated with respect to outcome measures.
Arm/Group Title Dose 1 (2.5 x 10^6/kg NK Cells) Dose 2 (5.0 x 10^6/kg NK Cells)
Hide Arm/Group Description:

CONDITIONING: Patients receive fludarabine IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1 hour on days -6 and -5. Patients undergo total-body irradiation on day -1.

DONOR BONE MARROW TRANSPLANTATION: Patients undergo donor bone marrow transplantation on day 0.

POST-TRANSPLANTATION IMMUNOSUPPRESSION: Patients receive cyclophosphamide IV over 1 hour on day 3 and mycophenolate mofetil PO TID on days 4 - 40, followed by a taper until day 84 in the absence of GVHD. Patients also receive tacrolimus IV continuously or IV QD over 1-2 hours or PO BID on days 4 - 84, followed by a taper until day 180 in the absence of GVHD.

NK CELL INFUSION: Patients undergo donor lymphocyte infusion of 2.5 x 10^6/kg NK cells on day 7.

Allogeneic Bone Marrow Transplantation: Undergo donor bone marrow transplantation

Laboratory Biomarker Analysis: Correlative studies

CONDITIONING: Patients receive fludarabine IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1 hour on days -6 and -5. Patients undergo total-body irradiation on day -1.

DONOR BONE MARROW TRANSPLANTATION: Patients undergo donor bone marrow transplantation on day 0.

POST-TRANSPLANTATION IMMUNOSUPPRESSION: Patients receive cyclophosphamide IV over 1 hour on day 3 and mycophenolate mofetil PO TID on days 4 - 40, followed by a taper until day 84 in the absence of GVHD. Patients also receive tacrolimus IV continuously or IV QD over 1-2 hours or PO BID on days 4 - 84, followed by a taper until day 180 in the absence of GVHD.

NK CELL INFUSION: Patients undergo donor lymphocyte infusion of 5.0 x 10^6/kg NK cells on day 7.

Allogeneic Bone Marrow Transplantation: Undergo donor bone marrow transplantation

Laboratory Biomarker Analysis: Correlative studies

Overall Number of Participants Analyzed 5 35
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
4
  11.4%
6.Secondary Outcome
Title Number of Subjects Surviving Post-transplant.
Hide Description Number of subjects surviving post-transplant.
Time Frame Up to 1 year
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
One subject aborted transplant after conditioning due to donor ineligibility. This subject was counted towards accrual but not evaluated with respect to outcome measures.
Arm/Group Title Dose 1 (2.5 x 10^6/kg NK Cells) Dose 2 (5.0 x 10^6/kg NK Cells)
Hide Arm/Group Description:

CONDITIONING: Patients receive fludarabine IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1 hour on days -6 and -5. Patients undergo total-body irradiation on day -1.

DONOR BONE MARROW TRANSPLANTATION: Patients undergo donor bone marrow transplantation on day 0.

POST-TRANSPLANTATION IMMUNOSUPPRESSION: Patients receive cyclophosphamide IV over 1 hour on day 3 and mycophenolate mofetil PO TID on days 4 - 40, followed by a taper until day 84 in the absence of GVHD. Patients also receive tacrolimus IV continuously or IV QD over 1-2 hours or PO BID on days 4 - 84, followed by a taper until day 180 in the absence of GVHD.

NK CELL INFUSION: Patients undergo donor lymphocyte infusion of 2.5 x 10^6/kg NK cells on day 7.

Allogeneic Bone Marrow Transplantation: Undergo donor bone marrow transplantation

Laboratory Biomarker Analysis: Correlative studies

CONDITIONING: Patients receive fludarabine IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1 hour on days -6 and -5. Patients undergo total-body irradiation on day -1.

DONOR BONE MARROW TRANSPLANTATION: Patients undergo donor bone marrow transplantation on day 0.

POST-TRANSPLANTATION IMMUNOSUPPRESSION: Patients receive cyclophosphamide IV over 1 hour on day 3 and mycophenolate mofetil PO TID on days 4 - 40, followed by a taper until day 84 in the absence of GVHD. Patients also receive tacrolimus IV continuously or IV QD over 1-2 hours or PO BID on days 4 - 84, followed by a taper until day 180 in the absence of GVHD.

NK CELL INFUSION: Patients undergo donor lymphocyte infusion of 5.0 x 10^6/kg NK cells on day 7.

Allogeneic Bone Marrow Transplantation: Undergo donor bone marrow transplantation

Laboratory Biomarker Analysis: Correlative studies

Overall Number of Participants Analyzed 5 35
Measure Type: Count of Participants
Unit of Measure: Participants
5
 100.0%
25
  71.4%
7.Secondary Outcome
Title Number of Participants Who Experienced Chronic Extensive GVHD
Hide Description Number of patients who developed chronic extensive GVHD post-transplant. The diagnosis of chronic GVHD requires at least one manifestation that is distinctive for chronic GVHD as opposed to acute GVHD. In all cases, infection and others causes must be ruled out in the differential diagnosis of chronic GVHD.
Time Frame Up to 1 year
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
One subject aborted transplant after conditioning due to donor ineligibility. This subject was counted towards accrual but not evaluated with respect to outcome measures.
Arm/Group Title Dose 1 (2.5 x 10^6/kg NK Cells) Dose 2 (5.0 x 10^6/kg NK Cells)
Hide Arm/Group Description:

CONDITIONING: Patients receive fludarabine IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1 hour on days -6 and -5. Patients undergo total-body irradiation on day -1.

DONOR BONE MARROW TRANSPLANTATION: Patients undergo donor bone marrow transplantation on day 0.

POST-TRANSPLANTATION IMMUNOSUPPRESSION: Patients receive cyclophosphamide IV over 1 hour on day 3 and mycophenolate mofetil PO TID on days 4 - 40, followed by a taper until day 84 in the absence of GVHD. Patients also receive tacrolimus IV continuously or IV QD over 1-2 hours or PO BID on days 4 - 84, followed by a taper until day 180 in the absence of GVHD.

NK CELL INFUSION: Patients undergo donor lymphocyte infusion of 2.5 x 10^6/kg NK cells on day 7.

Allogeneic Bone Marrow Transplantation: Undergo donor bone marrow transplantation

Laboratory Biomarker Analysis: Correlative studies

CONDITIONING: Patients receive fludarabine IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1 hour on days -6 and -5. Patients undergo total-body irradiation on day -1.

DONOR BONE MARROW TRANSPLANTATION: Patients undergo donor bone marrow transplantation on day 0.

POST-TRANSPLANTATION IMMUNOSUPPRESSION: Patients receive cyclophosphamide IV over 1 hour on day 3 and mycophenolate mofetil PO TID on days 4 - 40, followed by a taper until day 84 in the absence of GVHD. Patients also receive tacrolimus IV continuously or IV QD over 1-2 hours or PO BID on days 4 - 84, followed by a taper until day 180 in the absence of GVHD.

NK CELL INFUSION: Patients undergo donor lymphocyte infusion of 5.0 x 10^6/kg NK cells on day 7.

Allogeneic Bone Marrow Transplantation: Undergo donor bone marrow transplantation

Laboratory Biomarker Analysis: Correlative studies

Overall Number of Participants Analyzed 5 35
Measure Type: Count of Participants
Unit of Measure: Participants
2
  40.0%
3
   8.6%
Time Frame AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Dose 1 (2.5 x 10^6/kg NK Cells) Dose 2 (5.0 x 10^6/kg NK Cells)
Hide Arm/Group Description

CONDITIONING: Patients receive fludarabine IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1 hour on days -6 and -5. Patients undergo total-body irradiation on day -1.

DONOR BONE MARROW TRANSPLANTATION: Patients undergo donor bone marrow transplantation on day 0.

POST-TRANSPLANTATION IMMUNOSUPPRESSION: Patients receive cyclophosphamide IV over 1 hour on day 3 and mycophenolate mofetil PO TID on days 4 - 40, followed by a taper until day 84 in the absence of GVHD. Patients also receive tacrolimus IV continuously or IV QD over 1-2 hours or PO BID on days 4 - 84, followed by a taper until day 180 in the absence of GVHD.

NK CELL INFUSION: Patients undergo donor lymphocyte infusion of NK cells on day 7.

Allogeneic Bone Marrow Transplantation: Undergo donor bone marrow transplantation

Cyclophosphamide: Given IV

Fludarabine Phosphate: Given IV

Laboratory Biomarker Analysis: Correlative studies

Mycophenolate Mofetil: Given PO

Natural Killer Cell

CONDITIONING: Patients receive fludarabine IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1 hour on days -6 and -5. Patients undergo total-body irradiation on day -1.

DONOR BONE MARROW TRANSPLANTATION: Patients undergo donor bone marrow transplantation on day 0.

POST-TRANSPLANTATION IMMUNOSUPPRESSION: Patients receive cyclophosphamide IV over 1 hour on day 3 and mycophenolate mofetil PO TID on days 4 - 40, followed by a taper until day 84 in the absence of GVHD. Patients also receive tacrolimus IV continuously or IV QD over 1-2 hours or PO BID on days 4 - 84, followed by a taper until day 180 in the absence of GVHD.

NK CELL INFUSION: Patients undergo donor lymphocyte infusion of NK cells on day 7.

Allogeneic Bone Marrow Transplantation: Undergo donor bone marrow transplantation

Cyclophosphamide: Given IV

Fludarabine Phosphate: Given IV

Laboratory Biomarker Analysis: Correlative studies

Mycophenolate Mofetil: Given PO

Natural Killer Cell

All-Cause Mortality
Dose 1 (2.5 x 10^6/kg NK Cells) Dose 2 (5.0 x 10^6/kg NK Cells)
Affected / at Risk (%) Affected / at Risk (%)
Total   0/5 (0.00%)      10/35 (28.57%)    
Show Serious Adverse Events Hide Serious Adverse Events
Dose 1 (2.5 x 10^6/kg NK Cells) Dose 2 (5.0 x 10^6/kg NK Cells)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/5 (20.00%)      0/35 (0.00%)    
Metabolism and nutrition disorders     
Hyperkalemia   1/5 (20.00%)  1 0/35 (0.00%)  0
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%
Dose 1 (2.5 x 10^6/kg NK Cells) Dose 2 (5.0 x 10^6/kg NK Cells)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/5 (80.00%)      19/35 (54.29%)    
Blood and lymphatic system disorders     
Febrile neutropenia   0/5 (0.00%)  0 7/35 (20.00%)  7
Hemolytic uremic syndrome   0/5 (0.00%)  0 1/35 (2.86%)  1
Cardiac disorders     
Atrial fibrillation   0/5 (0.00%)  0 2/35 (5.71%)  2
Pericardial effusion   0/5 (0.00%)  0 1/35 (2.86%)  1
Congenital, familial and genetic disorders     
Urinary retention   0/5 (0.00%)  0 1/35 (2.86%)  1
Gastrointestinal disorders     
Diarrhea   0/5 (0.00%)  0 2/35 (5.71%)  2
Fecal incontinence   0/5 (0.00%)  0 1/35 (2.86%)  1
Gastroparesis   0/5 (0.00%)  0 1/35 (2.86%)  1
Obstruction gastric   0/5 (0.00%)  0 1/35 (2.86%)  1
Pancreatitis   0/5 (0.00%)  0 1/35 (2.86%)  2
General disorders     
Fever   0/5 (0.00%)  0 1/35 (2.86%)  1
Immune system disorders     
Allergic reaction   1/5 (20.00%)  1 1/35 (2.86%)  1
Infections and infestations     
Infections and infestations - Other, specify (E. Coli & Klebsiella)   0/5 (0.00%)  0 1/35 (2.86%)  1
Infections and infestations - Other, specify (Multiple)   0/5 (0.00%)  0 1/35 (2.86%)  1
Infections and infestations - Other, specify (viral/atypical bacterial infection vs. BOOP differenti   1/5 (20.00%)  1 0/35 (0.00%)  0
Sepsis   0/5 (0.00%)  0 2/35 (5.71%)  2
Urinary tract infection   0/5 (0.00%)  0 2/35 (5.71%)  2
Investigations     
Alanine aminotransferase increased   1/5 (20.00%)  1 2/35 (5.71%)  2
Creatinine increased   0/5 (0.00%)  0 1/35 (2.86%)  1
Renal and urinary disorders     
Acute kidney injury   0/5 (0.00%)  0 1/35 (2.86%)  1
Renal and urinary disorders - Other, specify (Focal thrombotic microangiopathy found on renal bx)   1/5 (20.00%)  1 0/35 (0.00%)  0
Urinary incontinence   0/5 (0.00%)  0 1/35 (2.86%)  1
Respiratory, thoracic and mediastinal disorders     
Hypoxia   1/5 (20.00%)  1 1/35 (2.86%)  1
Lung infection   1/5 (20.00%)  1 1/35 (2.86%)  1
Pleural effusion   1/5 (20.00%)  1 2/35 (5.71%)  2
Pulmonary edema   1/5 (20.00%)  1 0/35 (0.00%)  0
Respiratory failure   0/5 (0.00%)  0 1/35 (2.86%)  1
Vascular disorders     
Hypertension   1/5 (20.00%)  1 0/35 (0.00%)  0
Hypotension   1/5 (20.00%)  1 1/35 (2.86%)  2
Thromboembolic event   1/5 (20.00%)  1 2/35 (5.71%)  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
Name/Title: Dr. Brenda M. Sandmaier
Organization: Fred Hutchinson Cancer Research Center
Phone: (206) 667-4961
Responsible Party: Brenda Sandmaier, Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT00789776     History of Changes
Other Study ID Numbers: 2230.00
NCI-2010-00106 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2230.00 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
P01CA078902 ( U.S. NIH Grant/Contract )
P30CA015704 ( U.S. NIH Grant/Contract )
First Submitted: November 12, 2008
First Posted: November 13, 2008
Results First Submitted: May 2, 2018
Results First Posted: July 12, 2018
Last Update Posted: July 12, 2018