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 (OmitMMF)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Hematologic Neoplasms
• Intervention / Treatment: Other: Omission of the drug mycophenolate mofetil

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Amy Oppenheim; Phone Number: 310-423-3713; Email: Amy.Oppenheim@cshs.org
• Study Contact Backup: Name: Ronald Paquette, MD

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Recruiting
      • Cedars-Sinai Medical Center
      • Sub-Investigator: Akil Merchant, MD
      • Sub-Investigator: Justin Darrah, MD
      • Contact: Amy Oppenheim; Phone Number: 310-423-3713; Email: Amy.Oppenheim@cshs.org
      • Sub-Investigator: John Chute, MD
      • Sub-Investigator: Behrooz Hakimian, MD
      • Sub-Investigator: Noah Merin, MD
      • Sub-Investigator: Josh Sasine, MD
      • Sub-Investigator: Robert Vescio, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ronald Paquette
• Investigators: Principal Investigator: Ronald Paquette, MD, Cedars-Sinai Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2022
• Primary Completion (Estimated): September 30, 2024
• Study Completion (Estimated): September 30, 2024

Study Registration Dates

• First Submitted: January 27, 2022
• First Submitted That Met QC Criteria: February 16, 2022
• First Posted (Actual): February 25, 2022

Study Record Updates

• Last Update Posted (Actual): October 27, 2023
• Last Update Submitted That Met QC Criteria: October 25, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: allogeneic stem cell transplant
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms; Neoplasms by Site; Hematologic Diseases; Hematologic Neoplasms; Graft vs Host Disease; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antitubercular Agents; Antibiotics, Antitubercular; Mycophenolic Acid
• Other Study ID Numbers: IIT2021-11-PAQUETTE-OmitMMF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No