Fludarabine and Total Body Irradiation 800 Centigray (cGy) or 1125 cGy For Allogeneic Stem Cell Transplant Using Graft Versus Host Disease Prophylaxis With Post-Transplant Cyclophosphamide and Tacrolimus, Without Mycophenolate Mofetil

Study Overview
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Brief Summary
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This is a pilot study to evaluate the feasibility, safety and potential benefits of removing one immune suppressive drug called mycophenolate mofetil (MMF) from the standard allogenic stem cell transplant treatment protocol. MMF will be omitted from the transplant regimen in 60 eligible patients with hematologic malignancies. Participants will be followed for up to 2 years post standard of care transplant at Cedars-Sinai.

Official Title
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IIT2021-11-PAQUETTE-OmitMMF: Fludarabine and Total Body Irradiation 800 cGy or 1125 cGy For Allogeneic Stem Cell Transplant Using Graft Versus Host Disease Prophylaxis With Post-Transplant Cyclophosphamide and Tacrolimus, Without Mycophenolate Mofetil

Conditions
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Hematologic Neoplasms

Intervention / Treatment
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* Other: Omission of the drug mycophenolate mofetil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient age 18-75 years Patient has a related donor who is at least Human Leukocyte Antigen (HLA) haploidentical, or an unrelated donor who is a most a single HLA antigen mismatch. Patient signs the Informed Consent Form for the study Patient has a hematologic malignancy other than myelofibrosis and meets standard criteria for allogeneic stem cell transplant. Patient is deemed suitable to receive Fludarabine and Total Body Irradiation (Flu/TBI) 1125 or Flu/TBI 800 conditioning regimen as standard of care transplant Donor is willing to donate peripheral blood stem cells Exclusion Criteria: Patient has a diagnosis of myelofibrosis Patient has high titer antibodies against one or more donor HLA antigens Patient has undergone prior autologous or allogeneic stem cell transplant. Inability to collect sufficient peripheral blood stem cells from the donor

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open-label safety trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open Arm<br>Omission of the drug mycophenolate mofetil | Other: Omission of the drug mycophenolate mofetil<br>* Elimination of the immunosuppressive drug mycophenolate mofetil (MMF) from the post-transplant regimen.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Engraftment failure | Evaluate the feasibility of eliminating the drug Mycophenolate Mofetil (MMF) from the transplant regimens as determined by an acceptable rate of engraftment failure (<10%). Engraftment failure is when the blood-forming cells received on transplant day do not start to grow and make healthy blood cells. | 60 days post-transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to neutrophil and platelet engraftment | Days to neutrophil and platelet engraftment since transplant. | 60 days post-transplant | 
| Rate of severe acute GVHD by day +100. | Proportion of patients with severe acute GVHD at day 100 post-transplantation. Acute GVHD is when the donated stem cells attack the body within the first 100 days post-transplant. The modified Keystone criteria will be used for acute GVHD staging and grading. | 100 days post-transplant | 
| Treatment-related mortality | Rate of treatment-related mortality | 5 days post- transplant to 2-years | 
| Rate of severe chronic GVHD at 1 year | Proportion of patients with severe chronic GVHD at day 365 post-transplantation. -Chronic GVHD is when the donated stem cells attack the body after 100 days post-transplant. Chronic GVHD is defined by NIH Consensus Criteria for chronic GVHD. | 1-year post-transplant | 
| Relapse | Relapse rate at 1 and 2 years | 1 year post-transplant and 2 years post-transplant | 
| Overall Survival (OS) | Overall survival at 1 and 2 years | 1-year post-transplant and 2-years post-transplant | 
| Graft Versus Host Disease (GVHD)-free, Relapse Free Survival | Rate of GVHD-free, Relapse Free Survival | 1-year post- transplant and 2-years post-transplant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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allogeneic stem cell transplant