Clinical trial NCT01181271
Conditions: Diffuse, Large B-Cell, Lymphoma Lymphoma, Low-Grade T-Cell Lymphoma Mantle-Cell Lymphoma Hodgkin's Lymphoma Chronic Lymphocytic Leukemia Lymphoma, Small Lymphocytic
Keywords: Lymphoma non-hodgkins lymphoma Hodgkin's lymphoma Hodgkin's disease stem cell transplant High-risk diffuse large B cell Transformed low grade lymphoma T-cell non-Hodgkin's lymphoma Mantle cell lymphoma at any time in therapy "Double-hit" lymphoma
Sponsor: Massachusetts General Hospital
Start date: 2010-08-01; Completion date: 2016-02-01
Enrollment: 42 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
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.

Detailed description:
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.

Arms: arm 1: 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).
Interventions: intervention 1: Busulfan (conditioning for AUTO transplant) intervention 2: Etoposide (conditioning for AUTO transplant) intervention 3: Cyclophosphamide (conditioning for AUTO transplant) intervention 4: Mesna (prior to AUTO transplant) intervention 5: autologous (auto) peripheral blood stem cell transplantation intervention 6: Neupogen intervention 7: Fludarabine (conditioning for ALLO Transplant) intervention 8: Busulfan (conditioning for ALLO Transplant) intervention 9: non-myeloablative allogeneic (allo) transplant intervention 10: Tacrolimus intervention 11: Sirolimus intervention 12: Methotrexate
Intervention descriptions: intervention 1: 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 intervention 2: Etoposide 30 mg/kg IV bolus every day (QD) on day -4. The total daily dose of etoposide will be 30 mg/kg. intervention 3: Cyclophosphamide 60 mg/kg IV bolus QD on days -3 and -2. The total daily dose of cyclophosphamide will be 60 mg/kg. intervention 4: 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 intervention 5: Infusion of autologous peripheral blood stem cells on Day 0. intervention 6: 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 intervention 7: 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. intervention 8: 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 intervention 9: 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 intervention 10: Tacrolimus (FK506) will be given orally at a dose of 0.05 mg/kg orally (PO) twice a day (BID) starting day -3. intervention 11: 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 intervention 12: 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

Protocol documents: