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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

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Dose 1 (2.5 x 10^6/kg NK Cells)

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

Dose 2 (5.0 x 10^6/kg NK Cells)

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


Participant Flow:   Overall Study
    Dose 1 (2.5 x 10^6/kg NK Cells)   Dose 2 (5.0 x 10^6/kg NK Cells)
STARTED   5   36 
COMPLETED   5   35 
NOT COMPLETED   0   1 



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
One subject aborted transplant after conditioning due to donor ineligibility. This subject was counted towards accrual but not evaluated with respect to outcome measures.

Reporting Groups
  Description
Dose 1 (2.5 x 10^6/kg NK Cells)

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

Dose 2 (5.0 x 10^6/kg NK Cells)

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 Total of all reporting groups

Baseline Measures
   Dose 1 (2.5 x 10^6/kg NK Cells)   Dose 2 (5.0 x 10^6/kg NK Cells)   Total 
Overall Participants Analyzed 
[Units: Participants]
 5   36   41 
Age 
[Units: Participants]
Count of 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 
[Units: Years]
Median (Full Range)
 22.2 
 (14.5 to 43.7) 
 55.65 
 (8.1 to 75.2) 
 47.6 
 (8.1 to 75.2) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Female      2  40.0%      11  30.6%      13  31.7% 
Male      3  60.0%      25  69.4%      28  68.3% 
Ethnicity (NIH/OMB) 
[Units: Participants]
Count of 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) 
[Units: Participants]
Count of 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 
[Units: Participants]
Count of Participants
     
United States   5   36   41 


  Outcome Measures

1.  Primary:   Number of Participants With Dose Limiting Toxicities   [ Time Frame: Day 35 (28 days after NK cell infusion) ]

2.  Primary:   Number of Participants With Relapsed Disease   [ Time Frame: At 1 year ]

3.  Primary:   Number of Participants With Grades III-IV Acute GVHD   [ Time Frame: Day 100 ]

4.  Primary:   Number of Non-relapse Participant Mortalities   [ Time Frame: Day 200 ]

5.  Primary:   Number of Participants Who Experienced Graft Failure   [ Time Frame: Day 100 ]

6.  Secondary:   Number of Subjects Surviving Post-transplant.   [ Time Frame: Up to 1 year ]

7.  Secondary:   Number of Participants Who Experienced Chronic Extensive GVHD   [ Time Frame: Up to 1 year ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information

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
e-mail: bsandmai@fredhutch.org



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