Relapse remains a principle cause of treatment failure for patients with aggressive lymphoma after autologous transplantation. Non-myeloablative allogeneic transplantation allows patients to receive an infusion of donor cells in an attempt to induce a graft versus lymphoma effect. This study will assess the feasibility, safety and efficacy of the combination of autologous stem cell transplantation followed by non-myeloablative transplantation for patients with poor-risk aggressive lymphoma.
This is a phase II clinical trial investigating the feasibility, and efficacy of sequential autologous stem cell transplant followed by non-myeloablative allogeneic transplant for patients with poor risk lymphoma. Patients will be enrolled onto the trial when eligible and undergo standard high-dose chemotherapy with the combination with busulfan, cyclophosphamide, and etoposide followed by autologous stem cell transplant. After recovery of counts and clinical status, patients will then proceed to non-myeloablative allogeneic stem cell transplant using a fully matched related or unrelated donor.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
42
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
Etoposide 30 mg/kg IV bolus every day (QD) on day -4. The total daily dose of etoposide will be 30 mg/kg.
Cyclophosphamide 60 mg/kg IV bolus QD on days -3 and -2. The total daily dose of cyclophosphamide will be 60 mg/kg.
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 Mesna
Infusion of autologous peripheral blood stem cells on Day 0.
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
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.
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
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 weight
Tacrolimus (FK506) will be given orally at a dose of 0.05 mg/kg orally (PO) twice a day (BID) starting day -3.
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
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
Massachusetts General Hospital
Boston, Massachusetts, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Peripheral Blood All-cell Donor Chimerism
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.
Time frame: 100 days post allogeneic transplant
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)
Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening.
Time frame: within 200 days after allogeneic transplant
Cumulative Incidence of Extensive Chronic Graft-versus-host-disease
Extensive chronic graft versus-host-disease (GVHD) was defined as GVHD that required systemic immunosuppression.
Time frame: 1-year after allogeneic transplant
Cumulative Incidence of Non-relapse Mortality
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
Time frame: 2-years after allogeneic transplant
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
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