Adoptive Immunotherapy in Relapsed Hematological Malignancy: Early GVHD Prophylaxis
Condition: Hodgkin's Lymphoma; Lymphoid Leukemia; Lymphoma; Leukemia; Myeloma; Acute Lymphocytic Leukemia; Non Hodgkin Lymphoma; Chronic Lymphocytic Leukemia; Multiple Myeloma; Chronic Myelogenous Leukemia; Myelodysplastic Syndromes; Recurrent Acute Myeloid Leukemia, Adult; Recurrent Hodgkin Lymphoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Plasma Cell Myeloma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Chronic Myelogenous Leukemia; Acute Myelogenous Leukemia
MeSH terms: Lymphoma; Leukemia; Multiple Myeloma; Neoplasms, Plasma Cell; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Hodgkin Disease; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Hematologic Neoplasms; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes; Recurrence
Study type: Interventional
Phase: Phase 2

Summary: 
      Determine the relapse-free, donor lymphocyte infusion (DLI)-free survival in patients
      receiving the investigational regimen.This is a randomized phase II clinical trial, comparing
      two different dosing schedules of mycophenolate mofetil for graft versus host disease (GVHD)
      prevention following allogeneic stem cell transplantation. Risk for relapse, GVHD and
      non-relapse mortality will be assessed. Adaptive randomization between two study arms will be
      performed based on T cell counts at day 60.
    

Detailed description: 
      In this study, the investigators will utilize a regimen combining low dose total body
      irradiation and rabbit ATG to facilitate stem cell transplantation (SCT) with human leukocyte
      antigen (HLA) matched related and unrelated donors. Based on the hypothesis that early
      treatment interventions have significant late effects in allogeneic SCT, a simple
      intervention, varying the duration of intense immunosuppression following SCT, will be
      investigated in this study. This may allow more robust recovery of donor immune system cells
      in the first two months following transplantation and eventually result in lower risk of
      cancer relapse, while maintaining effective graft versus host disease (GVHD) control.
      Patients will be randomly assigned to receive GVHD prevention therapy using one of two
      different immunosuppressive regimens with tacrolimus & mycophenolate mofetil (MMF). Patients
      assigned to the investigational group will receive MMF for 15 days following SCT with growth
      factor support using granulocyte macrophage colony stimulating factor (GM-CSF) beginning on
      post-transplant day 4. Patients randomized to the standard treatment group will receive MMF
      for 30 days following SCT with cytokine support using granulocyte colony stimulating factor
      (G-CSF) beginning on post-transplant day 4. If one of these treatment groups demonstrates an
      improvement in donor immune cell recovery, there may be a slow increase in the likelihood of
      patients being assigned to that more successful treatment group. Eventually the two groups
      will be compared with respect to the likelihood of either relapse or GVHD developing.
    

Intervention name(s): mycophenolate mofetil; Sargramostim; Filgrastim
Intervention type(s): Drug; Biological; Biological
Intervention description(s): Given PO, by mouth, orally or IV, intravenous medication administration.; GM-CSF beginning post-transplant day 4 and continuing until hematopoietic reconstitution. Patients in the MMF-15 cohort will receive sargramostim (GM-CSF) 250 mcg/m2/day beginning on post-transplant day 4 and continuing until neutrophil engraftment.
Patients receiving GM-CSF will also receive inhaled corticosteroids, fluticasone (Flovent) 2 puffs twice daily, starting on post-transplant day 4 and stopping after cessation of GM-CSF, to diminish the risk of pneumonitis.
Note: At investigator discretion, patients in the MMF-15 cohort who have preexisting pulmonary risk factors, will be permitted to receive G-CSF.; G-CSF beginning post-transplant day 4 and continuing until hematopoietic reconstitution. Patients in the MMF-30 cohort will receive filgrastim (G-CSF) 5 mcg/kg/day beginning on post-transplant day 4 and continuing until neutrophil engraftment.
Other intervention name(s): CellCept; GM-CSF; colony stimulating factor 2; CSF2; granulocyte macrophage colony stimulating factor; G-CSF; GCSF; colony-stimulating factor 3; CSF 3; granulocyte colony stimulating factor
Intervention MeSH terms: Mycophenolic Acid; Molgramostim; Lenograstim; Sargramostim
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Donor Type (Matched Related Donor or Matched Unrelated Donor)