Haplo Peripheral Blood Sct In GVHD Prevention

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: Completed
• Conditions: Acute Myeloid Leukemia; Myelodysplastic Syndromes; Hodgkin Lymphoma; Chronic Myelomonocytic Leukemia; Acute Lymphoblastic Leukemia; AML; Non Hodgkin Lymphoma; MDS; Myeloproliferative Disorder; GVHD; Graft Vs Host Disease; ALL; CMML; Blood Stem Cell Transplant Failure; MPN; Chemosensitive Hodgkin Lymphoma
• Intervention / Treatment: Drug: FLUDARABINE; Drug: CYCLOPHOSPHAMIDE; Radiation: TBI; Drug: Sirolimus; Drug: Mycophenolate mofetil; Drug: RGI-2001; Drug: CYCLOPHOSPHAMIDE; Drug: Melphalan

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

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 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

How is the study designed?

Design Details

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

Number of Arms

2

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 cycleCyclophosphamide predetermined dose, predetermined number of times in cycle, intravenous infusionTotal body irradiation (TBI) once during treatment cycle; Post stem cell transplant:Cyclophosphamide predetermined dose, predetermined number of times in cycle, intravenous infusionSirolimus: 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 cycleRGI-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 cycleMelphalan, infusion, determined dosage, once per cycleTotal body irradiation (TBI) once per cycle.; Post stem cell transplantCyclophosphamide predetermined dose, predetermined number of times in cycle, intravenous infusionSirolimus: 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 cycleRGI-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	(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.	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

• Sponsor: Zachariah Michael DeFilipp
• Collaborators: Regimmune Corporation
• Investigators: Principal Investigator: Zachariah DeFilipp, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 14, 2020
• Primary Completion (Actual): October 22, 2023
• Study Completion (Actual): August 19, 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): July 20, 2025
• Last Update Submitted That Met QC Criteria: July 18, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia; MPN; AML; ALL; Acute Lymphoblastic Leukemia; MDS; Myelodysplastic Syndromes; GVHD; Non Hodgkin Lymphoma; CMML; Chronic Myelomonocytic Leukemia; Hodgkin Lymphoma; Graft Vs Host Disease; Blood Stem Cell Transplant Failure; Myeloproliferative Disorder; Chemosensitive Hodgkin Lymphoma
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Precancerous Conditions; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Lymphoma; Leukemia, Lymphoid; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Non-Hodgkin; Preleukemia; Myelodysplastic Syndromes; Myeloproliferative Disorders; Hodgkin Disease; Graft vs Host Disease; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antineoplastic; Antineoplastic Agents; Antifungal Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antibiotics, Antitubercular; Antitubercular Agents; Sirolimus; Cyclophosphamide; Fludarabine; Melphalan; Mycophenolic Acid
• 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
• product manufactured in and exported from the U.S.: No