Tandem Auto-Allo Transplant for Lymphoma
|ClinicalTrials.gov Identifier: NCT01181271|
Recruitment Status : Completed
First Posted : August 13, 2010
Results First Posted : March 9, 2017
Last Update Posted : March 9, 2017
|Condition or disease||Intervention/treatment||Phase|
|Diffuse, Large B-Cell, Lymphoma Lymphoma, Low-Grade T-Cell Lymphoma Mantle-Cell Lymphoma Hodgkin's Lymphoma Chronic Lymphocytic Leukemia Lymphoma, Small Lymphocytic||Drug: Busulfan (conditioning for AUTO transplant) Drug: Etoposide (conditioning for AUTO transplant) Drug: Cyclophosphamide (conditioning for AUTO transplant) Drug: Mesna (prior to AUTO transplant) Other: autologous (auto) peripheral blood stem cell transplantation Drug: Neupogen Drug: Fludarabine (conditioning for ALLO Transplant) Drug: Busulfan (conditioning for ALLO Transplant) Other: non-myeloablative allogeneic (allo) transplant Drug: Tacrolimus Drug: Sirolimus Drug: Methotrexate||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||42 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Sequential Myeloablative Autologous Stem Cell Transplantation Followed by Allogeneic Non-Myeloablative Stem Cell Transplantation for Patients With Poor Risk Lymphomas|
|Study Start Date :||August 2010|
|Actual Primary Completion Date :||February 2014|
|Actual Study Completion Date :||February 2016|
Experimental: Autologous then Allogeneic transplant
All patients will receive conditioning with busulfan, etoposide, and cyclophosphamide (with mesna) and then will undergo autologous (auto) peripheral blood stem cell transplantation.
Patients will be re-evaluated after autologous transplant prior to proceeding to non-myeloablative allogeneic (allo) transplant. If eligible to proceed, allogenic transplantation will take place no earlier than 40 days and no later than 180 days after autologous stem cell transplantation.
Conditioning for the allogeneic transplant will consist of fludarabine and busulfan. Participants will receive tacrolimus and sirolimus as prophylaxis against graft versus host disease (GVHD).
Drug: Busulfan (conditioning for AUTO transplant)
0.8 mg/kg intravenous (IV) bolus every six hours (Q6H) on days -8,-7,-6,-5 (total of 14 doses). The total daily dose of busulfan will be 3.2 mg/kg on days -8,-7, and -6 and 1.6 mg/kg on day -5
Other Name: BusulfexDrug: Etoposide (conditioning for AUTO transplant)
Etoposide 30 mg/kg IV bolus every day (QD) on day -4. The total daily dose of etoposide will be 30 mg/kg.
Other Name: VP-16Drug: Cyclophosphamide (conditioning for AUTO transplant)
Cyclophosphamide 60 mg/kg IV bolus QD on days -3 and -2. The total daily dose of cyclophosphamide will be 60 mg/kg.
Other Name: CytoxanDrug: Mesna (prior to AUTO transplant)
Mesna 15 mg/kg IV bolus on days -3 and -2 infused over 15 minutes and given 15 minutes prior to cyclophosphamide administration. This is followed by Mesna given 15 mg/kg IV bolus three times daily (TID) on days -3 and -2 infused over 15 minutes at 3, 6, and 9 hours after completion of cyclophosphamide infusion. Total daily dose of Mesna should be equivalent to daily dose of cyclophosphamide. Lastly, Mesna will be given at 15 mg/kg IV bolus QD on day -1. This makes a total of 9 doses of MesnaOther: autologous (auto) peripheral blood stem cell transplantation
Infusion of autologous peripheral blood stem cells on Day 0.Drug: Neupogen
Neupogen 5 mcg/kg subcutaneous (SQ) daily starting on day +1 until absolute neutrophil count (ANC) is greater than or equal to 1000 per micro liter on two separate occasions or greater than 5000 per micro liter once
Other Name: G-CSFDrug: Fludarabine (conditioning for ALLO Transplant)
Fludarabine 30 mg/m2/day will be administered as a bolus infusion over approximately 30 minutes for 4 days on days -5, -4, -3, -2.
Other Name: FludaraDrug: Busulfan (conditioning for ALLO Transplant)
Busulfan will be administered by IV infusion over approximately 3 hours on days -5, -4, -3, -2. The dose of busulfan will be 0.8 mg/kg/day
Other Name: BusulfexOther: non-myeloablative allogeneic (allo) transplant
Donor peripheral blood stem cells (PBSC) will be infused intravenously beginning on Day 0. The minimum total CD34+ cell dose will be 2 x 10^6 CD34+cells/kg of recipient's actual body weight with a maximum dose of 8 x 10^6/kg of recipient's actual body weightDrug: Tacrolimus
Tacrolimus (FK506) will be given orally at a dose of 0.05 mg/kg orally (PO) twice a day (BID) starting day -3.
Other Name: FK506Drug: Sirolimus
Sirolimus (rapamycin) will be given orally at a dose of 12 mg times one on day -3 and then the dose shall be 4 mg by mouth daily starting on day -2. The dose may then be adjusted according to serum levels at the discretion of the treating physician
Other Name: RapamycinDrug: Methotrexate
Methotrexate will be administered once daily on days 1, 3, and 6 as an IV bolus over 15 minutes at a dose of 5 mg/m2
- Peripheral Blood All-cell Donor Chimerism [ Time Frame: 100 days post allogeneic transplant ]Successful donor stem cell engraftment is defined as when ≥ 80% of hematopoietic elements are donor-derived as determined by chimerism assays from peripheral blood at day 100 after non-myeloablative allogeneic stem cell transplantation.
- Number of Days After Allogeneic Transplant Until Absolute Neutrophil Count Was Equal to or Greater Than 500/uL [ Time Frame: within 28 days after allogeneic transplant ]
- Cumulative Incidence of Grades II to IV Acute Graft Versus Host Disease (GVHD) [ Time Frame: within 200 days after allogeneic transplant ]Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening.
- Cumulative Incidence of Extensive Chronic Graft-versus-host-disease [ Time Frame: 1-year after allogeneic transplant ]Extensive chronic graft versus-host-disease (GVHD) was defined as GVHD that required systemic immunosuppression.
- Cumulative Incidence of Non-relapse Mortality [ Time Frame: 2-years after allogeneic transplant ]Non-relapse mortality is defined as participants who die from causes other than their underlying disease relapse, such as infection or graft versus host disease
- Cumulative Incidence of Disease Relapse [ Time Frame: 2-years after allogeneic transplant ]
- Estimated Two Year Progression Free Survival Rate for Participants Undergoing Both Autologous and Allogeneic Transplants [ Time Frame: 2 years after allogeneic transplant ]
- Estimated Two Year Overall Survival Rate for Participants Undergoing Both Autologous and Allogeneic Transplants [ Time Frame: Two-years after Allogeneic Transplant ]
- Estimated Two Year Progression Free Survival Rate for All Participants [ Time Frame: 2 years ]
- Estimated Two Year Overall Survival Rate for All Participants [ Time Frame: 2 years ]
- Estimated Two Year Progression Free Survival Rate for Participants Undergoing Only Autologous Transplant [ Time Frame: Two Years ]
- Estimated Two Year Overall Survival Rate for Participants Undergoing Only Autologous Transplant [ Time Frame: two years ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01181271
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|Dana Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|Principal Investigator:||Yi-Bin A Chen, MD||Massachusetts General Hospital|