Trial Outcomes & Findings for 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 (NCT NCT00789776)
NCT ID: NCT00789776
Last Updated: 2020-01-31
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
41 participants
Primary outcome timeframe
Day 35 (28 days after NK cell infusion)
Results posted on
2020-01-31
Participant Flow
Participant milestones
| Measure |
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
|
|---|---|---|
|
Overall Study
STARTED
|
5
|
36
|
|
Overall Study
COMPLETED
|
5
|
35
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
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
Baseline characteristics by cohort
| Measure |
Dose 1 (2.5 x 10^6/kg NK Cells)
n=5 Participants
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)
n=36 Participants
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
n=41 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
1 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
4 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
27 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Age, Continuous
|
22.2 years
n=5 Participants
|
55.65 years
n=7 Participants
|
47.6 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
4 Participants
n=5 Participants
|
31 Participants
n=7 Participants
|
35 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
32 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
5 Participants
n=5 Participants
|
36 Participants
n=7 Participants
|
41 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 35 (28 days after NK cell infusion)Population: One subject aborted transplant after conditioning due to donor ineligibility. This subject was counted towards accrual but not evaluated with respect to outcome measures.
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.
Outcome measures
| Measure |
Dose 1 (2.5 x 10^6/kg NK Cells)
n=5 Participants
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)
n=35 Participants
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
|
|---|---|---|
|
Number of Participants With Dose Limiting Toxicities
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: At 1 yearPopulation: One subject aborted transplant after conditioning due to donor ineligibility. This subject was counted towards accrual but not evaluated with respect to outcome measures.
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.
Outcome measures
| Measure |
Dose 1 (2.5 x 10^6/kg NK Cells)
n=5 Participants
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)
n=35 Participants
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
|
|---|---|---|
|
Number of Participants With Relapsed Disease
|
1 Participants
|
10 Participants
|
PRIMARY outcome
Timeframe: Day 100Population: One subject aborted transplant after conditioning due to donor ineligibility. This subject was counted towards accrual but not evaluated with respect to outcome measures.
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
Outcome measures
| Measure |
Dose 1 (2.5 x 10^6/kg NK Cells)
n=5 Participants
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)
n=35 Participants
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
|
|---|---|---|
|
Number of Participants With Grades III-IV Acute GVHD
|
1 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Day 200Population: One subject aborted transplant after conditioning due to donor ineligibility. This subject was counted towards accrual but not evaluated with respect to outcome measures.
Defined as death in any patient for whom there has not been a diagnosis of relapse or disease progression.
Outcome measures
| Measure |
Dose 1 (2.5 x 10^6/kg NK Cells)
n=5 Participants
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)
n=35 Participants
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
|
|---|---|---|
|
Number of Non-relapse Participant Mortalities
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Day 100Population: One subject aborted transplant after conditioning due to donor ineligibility. This subject was counted towards accrual but not evaluated with respect to outcome measures.
Graft failure is defined as grade IV thrombocytopenia and neutropenia after Day +21 that lasts \>2 weeks and is refractory to growth factor support.
Outcome measures
| Measure |
Dose 1 (2.5 x 10^6/kg NK Cells)
n=5 Participants
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)
n=35 Participants
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
|
|---|---|---|
|
Number of Participants Who Experienced Graft Failure
|
0 Participants
|
4 Participants
|
SECONDARY outcome
Timeframe: Up to 1 yearPopulation: One subject aborted transplant after conditioning due to donor ineligibility. This subject was counted towards accrual but not evaluated with respect to outcome measures.
Number of subjects surviving post-transplant.
Outcome measures
| Measure |
Dose 1 (2.5 x 10^6/kg NK Cells)
n=5 Participants
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)
n=35 Participants
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
|
|---|---|---|
|
Number of Subjects Surviving Post-transplant.
|
5 Participants
|
25 Participants
|
SECONDARY outcome
Timeframe: Up to 1 yearPopulation: One subject aborted transplant after conditioning due to donor ineligibility. This subject was counted towards accrual but not evaluated with respect to outcome measures.
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.
Outcome measures
| Measure |
Dose 1 (2.5 x 10^6/kg NK Cells)
n=5 Participants
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)
n=35 Participants
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
|
|---|---|---|
|
Number of Participants Who Experienced Chronic Extensive GVHD
|
2 Participants
|
3 Participants
|
Adverse Events
Dose 1 (2.5 x 10^6/kg NK Cells)
Serious events: 1 serious events
Other events: 4 other events
Deaths: 0 deaths
Dose 2 (5.0 x 10^6/kg NK Cells)
Serious events: 0 serious events
Other events: 19 other events
Deaths: 10 deaths
Serious adverse events
| Measure |
Dose 1 (2.5 x 10^6/kg NK Cells)
n=5 participants at risk
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
|
Dose 2 (5.0 x 10^6/kg NK Cells)
n=35 participants at risk
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
|
|---|---|---|
|
Metabolism and nutrition disorders
Hyperkalemia
|
20.0%
1/5 • Number of events 1 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
0.00%
0/35 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
Other adverse events
| Measure |
Dose 1 (2.5 x 10^6/kg NK Cells)
n=5 participants at risk
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
|
Dose 2 (5.0 x 10^6/kg NK Cells)
n=35 participants at risk
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
|
|---|---|---|
|
Renal and urinary disorders
Acute kidney injury
|
0.00%
0/5 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
2.9%
1/35 • Number of events 1 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
|
Investigations
Alanine aminotransferase increased
|
20.0%
1/5 • Number of events 1 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
5.7%
2/35 • Number of events 2 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
|
Immune system disorders
Allergic reaction
|
20.0%
1/5 • Number of events 1 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
2.9%
1/35 • Number of events 1 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/5 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
5.7%
2/35 • Number of events 2 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
|
Investigations
Creatinine increased
|
0.00%
0/5 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
2.9%
1/35 • Number of events 1 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/5 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
5.7%
2/35 • Number of events 2 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/5 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
20.0%
7/35 • Number of events 7 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
|
Gastrointestinal disorders
Fecal incontinence
|
0.00%
0/5 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
2.9%
1/35 • Number of events 1 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
|
General disorders
Fever
|
0.00%
0/5 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
2.9%
1/35 • Number of events 1 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
|
Gastrointestinal disorders
Gastroparesis
|
0.00%
0/5 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
2.9%
1/35 • Number of events 1 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
|
Blood and lymphatic system disorders
Hemolytic uremic syndrome
|
0.00%
0/5 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
2.9%
1/35 • Number of events 1 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
|
Vascular disorders
Hypertension
|
20.0%
1/5 • Number of events 1 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
0.00%
0/35 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
|
Vascular disorders
Hypotension
|
20.0%
1/5 • Number of events 1 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
2.9%
1/35 • Number of events 2 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
20.0%
1/5 • Number of events 1 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
2.9%
1/35 • Number of events 1 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
|
Infections and infestations
Infections and infestations - Other, specify (E. Coli & Klebsiella)
|
0.00%
0/5 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
2.9%
1/35 • Number of events 1 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
|
Infections and infestations
Infections and infestations - Other, specify (Multiple)
|
0.00%
0/5 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
2.9%
1/35 • Number of events 1 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
|
Infections and infestations
Infections and infestations - Other, specify (viral/atypical bacterial infection vs. BOOP differenti
|
20.0%
1/5 • Number of events 1 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
0.00%
0/35 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
|
Respiratory, thoracic and mediastinal disorders
Lung infection
|
20.0%
1/5 • Number of events 1 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
2.9%
1/35 • Number of events 1 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
|
Gastrointestinal disorders
Obstruction gastric
|
0.00%
0/5 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
2.9%
1/35 • Number of events 1 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/5 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
2.9%
1/35 • Number of events 2 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
|
Cardiac disorders
Pericardial effusion
|
0.00%
0/5 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
2.9%
1/35 • Number of events 1 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
20.0%
1/5 • Number of events 1 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
5.7%
2/35 • Number of events 2 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary edema
|
20.0%
1/5 • Number of events 1 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
0.00%
0/35 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
|
Renal and urinary disorders
Renal and urinary disorders - Other, specify (Focal thrombotic microangiopathy found on renal bx)
|
20.0%
1/5 • Number of events 1 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
0.00%
0/35 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/5 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
2.9%
1/35 • Number of events 1 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
|
Infections and infestations
Sepsis
|
0.00%
0/5 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
5.7%
2/35 • Number of events 2 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
|
Vascular disorders
Thromboembolic event
|
20.0%
1/5 • Number of events 1 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
5.7%
2/35 • Number of events 3 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
|
Renal and urinary disorders
Urinary incontinence
|
0.00%
0/5 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
2.9%
1/35 • Number of events 1 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
|
Congenital, familial and genetic disorders
Urinary retention
|
0.00%
0/5 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
2.9%
1/35 • Number of events 1 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/5 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
5.7%
2/35 • Number of events 2 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
|
Additional Information
Dr. Brenda M. Sandmaier
Fred Hutchinson Cancer Research Center
Phone: (206) 667-4961
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place