Adoptive Immunotherapy in Relapsed Hematological Malignancy: Early GVHD Prophylaxis

Phase 2

Completed

Conditions: Hodgkin's Lymphoma
Acute Lymphocytic Leukemia
Chronic Lymphocytic Leukemia
Myelodysplastic Syndromes
Recurrent Non-Hodgkin Lymphoma
Recurrent Chronic Lymphocytic Leukemia
Non Hodgkin Lymphoma
Multiple Myeloma
Chronic Myelogenous Leukemia
Recurrent Hodgkin Lymphoma

Interventions: Drug: mycophenolate mofetil
Biological: Filgrastim
Biological: Sargramostim

Registration Number: NCT02593123

Lead Sponsor: Virginia Commonwealth University

Brief 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 31

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm II (MMF-30, filgrastim)	Filgrastim	Patients receive mycophenolate mofetil PO or IV (twice daily) BID on days 0-30 and filgrastim G-CSF from post-transplant day 4 until neutrophil engraftment.
Arm I (MMF-15, sargramostim)	mycophenolate mofetil	Patients receive mycophenolate mofetil (MMF) PO or IV twice daily (BID) on days 0-15 and sargramostim SC from post-transplant day 4 until neutrophil engraftment.
Arm I (MMF-15, sargramostim)	Sargramostim	Patients receive mycophenolate mofetil (MMF) PO or IV twice daily (BID) on days 0-15 and sargramostim SC from post-transplant day 4 until neutrophil engraftment.
Arm II (MMF-30, filgrastim)	mycophenolate mofetil	Patients receive mycophenolate mofetil PO or IV (twice daily) BID on days 0-30 and filgrastim G-CSF from post-transplant day 4 until neutrophil engraftment.

Primary Outcome Measures

Name	Time	Method
The Number of Patients With Relapse-free/Donor Lymphocyte Infusion(DLI)-Free Survival Rates Between Patients Randomized to MMF-30 (Control Cohort) and MMF-15 (Investigational Cohort).	Up to 2 years following stem cell transplant	The primary outcome in this study is event-free survival, where the conditional events are the occurrence of relapse DLI.

Secondary Outcome Measures

Name	Time	Method
Differences Between Patients Randomized to MMF-30 (Control Cohort) and MMF-15 (Investigational Cohort) With Acute Graft Vs Host Disease (GVHD)	60 Days following stem cell transplant	The number of patients diagnosed with acute acute GVHD between patients randomized to MMF-30 (control cohort) and MMF-15 (investigational cohort)
Differences Between Patients Randomized to MMF-30 (Control Cohort) and MMF-15 (Investigational Cohort) Diagnosed With Opportunistic Infections	60 Days following stem cell transplant	The number of patients diagnosed with an opportunistic infections.
Differences in the Rates of T-cell Recovery Kinetics Following Stem Cell Transplantation (SCT) Between Patients Randomized to MMF-30 (Control Cohort) and MMF-15 (Investigational Cohort).	100 Days Following Stem Cell Transplantation	Number of T Cells 10E3 per microL per arm indicating rates of T-cell recovery by Day 100 following SCT.
Determine the Differences Between Patients Randomized to MMF-30 (Control Cohort) and MMF-15 (Investigational Cohort) With Diagnosis of Engraftment Loss.	60 Days Following Stem Cell Transplant	Number of patients with engraftment loss.
Differences in the Rates of Achieving Donor Chimerisms (the Percentage of DNA in the Sample Which Comes From the Donor) Between Patients Randomized to MMF-30 (Control Cohort) and MMF-15 (Investigational Cohort).	100 Days following Stem Cell Transplant	Number of patients that achieved donor chimerisms by day 100.
The Difference Between Patients Randomized to MMF-30 (Control Cohort) and MMF-15 (Investigational Cohort) Day 60 Donor-derived (dd) Cluster of Differentiation (CD)3 10E3per microL Counts.	60 Days Following Stem Cell Transplant	Day 60 donor-derived (dd) cluster of differentiation (CD)3 counts measured by 10E3per microL.
The Probability of Overall Survival (OS) Between Patients Randomized to MMF-30 (Control Cohort) and MMF-15 (Investigational Cohort)	Randomization up to 2 years	Overall survival (days to event or survival: time-to-event; survival: categorical)
Differences Between Patients Randomized to MMF-30 (Control Cohort) and MMF-15 (Investigational Cohort) Diagnosed With Chronic Graft vs Host Disease (GVHD)	60 Days following stem cell transplant	The differences in the rates of chronic GVHD between patients randomized to MMF-30 (control cohort) and MMF-15 (investigational cohort)
Differences Between Patients Randomized to MMF-30 (Control Cohort) and MMF-15 (Investigational Cohort)Diagnosed With Differences in the Rates of Engraftment Syndrome.	60 Days Following Stem Cell Transplant	Number of patients diagnosed with engraftment syndrome.