Tandem Auto-Allo Transplant for Lymphoma
Condition: Diffuse, Large B-Cell, Lymphoma; Lymphoma, Low-Grade; T-Cell Lymphoma; Mantle-Cell Lymphoma; Hodgkin's Lymphoma; Chronic Lymphocytic Leukemia; Lymphoma, Small Lymphocytic
MeSH terms: Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell; Hodgkin Disease; Lymphoma, Mantle-Cell; Lymphoma, Non-Hodgkin; Lymphoma, Large B-Cell, Diffuse
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Busulfan (conditioning for AUTO transplant); Etoposide (conditioning for AUTO transplant); Cyclophosphamide (conditioning for AUTO transplant); Mesna (prior to AUTO transplant); autologous (auto) peripheral blood stem cell transplantation; Neupogen; Fludarabine (conditioning for ALLO Transplant); Busulfan (conditioning for ALLO Transplant); non-myeloablative allogeneic (allo) transplant; Tacrolimus; Sirolimus; Methotrexate
Intervention type(s): Drug; Drug; Drug; Drug; Other; Drug; Drug; Drug; Other; Drug; Drug; Drug
Intervention description(s): 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
Other intervention name(s): Busulfex; VP-16; Cytoxan; G-CSF; Fludara; Busulfex; FK506; Rapamycin
Intervention MeSH terms: Sirolimus; Cyclophosphamide; Busulfan; Methotrexate; Fludarabine; Etoposide; Tacrolimus
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
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