Haplo Peripheral Blood Sct In GVHD Prevention

March 6, 2024 updated by: Zachariah Michael DeFilipp

Reduced Intensity Haploidentical Peripheral Blood Stem Cell Transplantation With Post-transplant Cyclophosphamide and Sirolimus/Mycophenolate Mofetil/RGI-2001 Based GVHD Prevention: a Pilot Study

This research study is studying the RGI-2001 for preventing Graft-vs-Host Disease (GVHD) in people with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), myelodysplastic syndrome (MDS), myeloproliferative disorders (MPN), chronic myelomonocytic leukemic (CMML), chemosensitive hodgkin lymphoma (HL), or Non-Hodgkin lymphoma (NHL).who will have a blood stem cell transplantation.

  • GVHD is a condition in which cells from the donor's tissue attack the organs.
  • RGI-2001 is an investigational treatment

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

  • This is a pilot study in subjects undergoing reduced-intensity haploidentical peripheral blood stem cell transplantation who will receive graft-versus-host disease prevention with post-transplant cyclophosphamide, followed by sirolimus, mycophenolate mofetil, and RGI-2001.
  • The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.

  • The standard of care drugs of fludarabine, cyclophosphamide, melphalan, radiation, sirolimus, and mycophenolate mofetil are all FDA approved.

    • Eligible Participants will be placed in 1 of 2 groups, per physicians discretion:

    • Regimen #1 :

      • Before stem cell transplant:Fludarabine + Cyclophosphamide + Radiation
      • After stem cell transplant: Cyclophosphamide + Sirolimus +Mycophenolate mofetil + RGI-2001

    • Regimen #2

      • Before stem cell transplant: fludarabine + melphalan + radiation
      • After stem cell transplant: cyclophosphamide + sirolimus +Mycophenolate mofetil + RGI-2001
  • A total of 20 participants will be enrolled to this trial
  • The U.S. Food and Drug Administration (FDA) has not approved RGI-2001 as a treatment for any disease.

Study Type

Interventional

Enrollment (Actual)

25

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Massachusetts General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 78 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Men or women ≥ 18 and ≤ 80 years old

  • Diagnosis of hematological malignancy:

    • Acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) in morphologic complete remission
    • Myelodysplastic syndrome (MDS), myeloproliferative disorders (MPN), or chronic myelomonocytic leukemic (CMML) with < 5% blasts in blood or bone marrow
    • Chemosensitive Hodgkin lymphoma (HL) or Non-Hodgkin lymphoma (NHL)
  • Patients must be undergoing haploidentical allogeneic hematopoietic cell transplantation, defined as 1st or 2nd degree relative with at least 5/10 matching at HLA-A, -B, -C, DR, and DQ.
  • ECOG performance status ≤2

  • Patients with adequate physical function as measured by:

    • Cardiac: Left ventricular ejection fraction at rest must be ≥ 40%, or shortening fraction >25%

    • Hepatic:

      • Bilirubin ≤ 2.5 mg/dL, except for patients with Gilbert's syndrome or hemolysis
      • ALT, AST, and Alkaline Phosphatase < 5 x ULN
    • Renal: Serum creatinine within normal range, or if serum creatinine is outside normal range, then renal function (measured or estimated creatinine clearance or GFR) ≥ 40mL/min/1.73m2
    • Pulmonary: DLCO (corrected for hemoglobin), FEV1 and FVC ≥ 50% predicted
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Prior allogeneic hematopoietic stem cell transplantation. (Patients may have received a prior autologous hematopoietic stem cell transplant.)
  • Participants who are receiving any other investigational agents within 14 days prior to RGI-2001 dosing. Thus, participants must stop investigational agents by Day -9 prior to transplant.
  • Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, recent myocardial infarction or stroke, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Patients with active or uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
  • Planned use of prophylactic donor lymphocyte infusion (DLI) therapy.
  • Pregnant and breast-feeding women are ineligible because they are not eligible for hematopoietic stem cell transplantation.
  • HIV-positive participants and patients with active Hepatitis B or C are ineligible

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Regimen 1: Fludarabine, Cyclophosphamide, and TBI

-. Patients who meet eligibility criteria for the study will subsequently be enrolled for treatment. Two reduced intensity regimens will be allowed, according to the choice of the treating physician

  • Pre- stem cell transplant:

    • Fludarabine predetermined dose, intravenously, 4 times per cycle
    • Cyclophosphamide predetermined dose, predetermined number of times in cycle, intravenous infusion
    • Total body irradiation (TBI) once during treatment cycle

  • Post stem cell transplant:

    • Cyclophosphamide predetermined dose, predetermined number of times in cycle, intravenous infusion
    • Sirolimus: Predetermined dosage, predetermined number of time in cycle, oral.
    • Mycophenolate mofetil, oral or iv(predetermined dose or IV TID (based upon actual body weight), at predetermined times per cycle
    • RGI-2001: IV, predetermined dose, weekly to 6 total doses
Drug: FLUDARABINE
predetermined dose, intravenously, a predetermined times per cycle Given in both pre stem cell and post stem cell cycles
Other Names:
  • Fludara®
Drug: CYCLOPHOSPHAMIDE
◦Cyclophosphamide predetermined dose, predetermined number of times in Given in pre-stem cell Regimen #1 Cyclophosphamide predetermined dose, predetermined number of times in cycle, intravenous infusion
Other Names:
  • Cytoxan®
  • Neosar®
Radiation: TBI
Total body irradiation (TBI) once per cycle.
Drug: Sirolimus
Sirolimus: Predetermined dosage, predetermined number of time in cycle, oral: Please note that doses of sirolimus can be adjusted at the treating physician's discretion given the multiple drugs and other situations which affect its metabolism
Other Names:
  • Rapamune
Drug: Mycophenolate mofetil
◦Mycophenolate mofetil, oral or iv(predetermined dose or IV TID (based upon actual body weight), at predetermined times per cycle
Other Names:
  • CellCept
  • Myfortic
Drug: RGI-2001
IV, predetermined dose, weekly to 6 total doses
Drug: CYCLOPHOSPHAMIDE
◦Given in Post Stem Cell cycle of Regimen #1 and #2 Cyclophosphamide predetermined dose, predetermined number of times in cycle, intravenous infusion
Other Names:
  • Cytoxan®
  • Neosar®
Experimental: Regimen 2: Fludarabine, Melphalan, and TBI

-. Patients who meet eligibility criteria for the study will subsequently be enrolled for treatment. Two reduced intensity regimens will be allowed, according to the choice of the treating physician

  • Pre- stem cell transplant:

    • Fludarabine predetermined dose, intravenously 3 times per cycle
    • Melphalan, infusion, determined dosage, once per cycle
    • Total body irradiation (TBI) once per cycle.

  • Post stem cell transplant

    • Cyclophosphamide predetermined dose, predetermined number of times in cycle, intravenous infusion
    • Sirolimus: Predetermined dosage, predetermined number of time in cycle, oral:
    • Mycophenolate mofetil, oral or iv(predetermined dose or IV TID (based upon actual body weight), at predetermined times per cycle
    • RGI-2001: IV, predetermined dose, weekly to 6 total doses
Drug: FLUDARABINE
predetermined dose, intravenously, a predetermined times per cycle Given in both pre stem cell and post stem cell cycles
Other Names:
  • Fludara®
Drug: CYCLOPHOSPHAMIDE
◦Cyclophosphamide predetermined dose, predetermined number of times in Given in pre-stem cell Regimen #1 Cyclophosphamide predetermined dose, predetermined number of times in cycle, intravenous infusion
Other Names:
  • Cytoxan®
  • Neosar®
Radiation: TBI
Total body irradiation (TBI) once per cycle.
Drug: Sirolimus
Sirolimus: Predetermined dosage, predetermined number of time in cycle, oral: Please note that doses of sirolimus can be adjusted at the treating physician's discretion given the multiple drugs and other situations which affect its metabolism
Other Names:
  • Rapamune
Drug: Mycophenolate mofetil
◦Mycophenolate mofetil, oral or iv(predetermined dose or IV TID (based upon actual body weight), at predetermined times per cycle
Other Names:
  • CellCept
  • Myfortic
Drug: RGI-2001
IV, predetermined dose, weekly to 6 total doses
Drug: CYCLOPHOSPHAMIDE
◦Given in Post Stem Cell cycle of Regimen #1 and #2 Cyclophosphamide predetermined dose, predetermined number of times in cycle, intravenous infusion
Other Names:
  • Cytoxan®
  • Neosar®
Drug: Melphalan
Melphalan, infusion, determined dosage, once per cycle
Other Names:
  • L-PAM
  • L-Sarcolysin
  • Phenylalanine Mustard
  • Alkeran®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients achieving successful donor engraftment
Time Frame: 60 Days
(absolute neutrophil count > 500/uL and ≥ 90% donor cell chimerism)
60 Days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
100-day non-relapse mortality (NRM) rate.
Time Frame: 100 Days
The regimen will be considered as safe if 100d NRM rate is <=5%, and not safe if 100d NRM rate is ≥25%.
100 Days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Zachariah Michael DeFilipp

Collaborators

Regimmune Corporation

Investigators

  • Principal Investigator: Zachariah DeFilipp, MD, Massachusetts General Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 14, 2020

Primary Completion (Actual)

October 22, 2023

Study Completion (Estimated)

October 1, 2024

Study Registration Dates

First Submitted

July 13, 2020

First Submitted That Met QC Criteria

July 13, 2020

First Posted (Actual)

July 16, 2020

Study Record Updates

Last Update Posted (Actual)

March 7, 2024

Last Update Submitted That Met QC Criteria

March 6, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 19-336

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to, please contact the Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

IPD Sharing Time Frame

Data can be shared no earlier than 1 year following the date of publication

IPD Sharing Access Criteria

Contact the Partners Innovations team at http://www.partners.org/innovation

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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