Haplo Peripheral Blood Sct In GVHD Prevention

NCT04473911 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 19-336
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

GVHD; AML; ALL; MDS; MPN; CMML; Hodgkin Lymphoma; Non Hodgkin Lymphoma; Blood Stem Cell Transplant Failure; Graft Vs Host Disease; Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Myelodysplastic Syndromes; Myeloproliferative Disorder; Chronic Myelomonocytic Leukemia; Chemosensitive Hodgkin Lymphoma

Keywords

GVHD; AML; ALL; MDS; MPN; CMML; Hodgkin Lymphoma; Non Hodgkin Lymphoma; Blood Stem Cell Transplant Failure; Graft Vs Host Disease; Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Myelodysplastic Syndromes; Myeloproliferative Disorder; Chronic Myelomonocytic Leukemia; Chemosensitive Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• Number of patients achieving successful donor engraftment

  (absolute neutrophil count \> 500/uL and ≥ 90% donor cell chimerism)

  60 Days

Secondary Outcomes (1)

• 100-day non-relapse mortality (NRM) rate.

  100 Days

Study Arms (2)

Regimen 1: Fludarabine, Cyclophosphamide, and TBI

EXPERIMENTAL

-. 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; Drug: CYCLOPHOSPHAMIDE; Radiation: TBI; Drug: Sirolimus; Drug: Mycophenolate mofetil; Drug: RGI-2001

Regimen 2: Fludarabine, Melphalan, and TBI

EXPERIMENTAL

-. 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; Radiation: TBI; Drug: Melphalan; Drug: Sirolimus; Drug: Mycophenolate mofetil; Drug: RGI-2001; Drug: CYCLOPHOSPHAMIDE

Interventions

FLUDARABINE DRUG

predetermined dose, intravenously, a predetermined times per cycle Given in both pre stem cell and post stem cell cycles

Also known as: Fludara®

Regimen 1: Fludarabine, Cyclophosphamide, and TBI; Regimen 2: Fludarabine, Melphalan, and TBI

CYCLOPHOSPHAMIDE DRUG

◦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

Also known as: Cytoxan®, Neosar®

Regimen 1: Fludarabine, Cyclophosphamide, and TBI

TBI RADIATION

Total body irradiation (TBI) once per cycle.

Regimen 1: Fludarabine, Cyclophosphamide, and TBI; Regimen 2: Fludarabine, Melphalan, and TBI

Melphalan DRUG

Melphalan, infusion, determined dosage, once per cycle

Also known as: Alkeran®, L-PAM, L-Sarcolysin, Phenylalanine Mustard

Regimen 2: Fludarabine, Melphalan, and TBI

Sirolimus DRUG

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

Also known as: Rapamune

Regimen 1: Fludarabine, Cyclophosphamide, and TBI; Regimen 2: Fludarabine, Melphalan, and TBI

Mycophenolate mofetil DRUG

◦Mycophenolate mofetil, oral or iv(predetermined dose or IV TID (based upon actual body weight), at predetermined times per cycle

Also known as: CellCept, Myfortic

Regimen 1: Fludarabine, Cyclophosphamide, and TBI; Regimen 2: Fludarabine, Melphalan, and TBI

RGI-2001 DRUG

IV, predetermined dose, weekly to 6 total doses

Regimen 1: Fludarabine, Cyclophosphamide, and TBI; Regimen 2: Fludarabine, Melphalan, and TBI

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Zachariah Michael DeFilipp: lead
• Regimmune Corporation: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Hodgkin Disease; Lymphoma, Non-Hodgkin; Graft vs Host Disease; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes; Myeloproliferative Disorders; Leukemia, Myelomonocytic, Chronic

Interventions

fludarabine; fludarabine phosphate; Cyclophosphamide; Melphalan; Sirolimus; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Leukemia; Hematologic Diseases; Leukemia, Lymphoid; Bone Marrow Diseases; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Macrolides; Lactones; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Study Officials

• Zachariah DeFilipp, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: July 13, 2020
• First Posted: July 16, 2020
• Study Start: August 14, 2020
• Primary Completion: October 22, 2023
• Study Completion: August 19, 2024
• Last Updated: July 20, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (1)