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Haplo Peripheral Blood Sct In GVHD Prevention

Primary Purpose

GVHD, AML, ALL

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
FLUDARABINE
CYCLOPHOSPHAMIDE
TBI
Melphalan
Sirolimus
Mycophenolate mofetil
RGI-2001
CYCLOPHOSPHAMIDE
Sponsored by
Zachariah Michael DeFilipp
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for GVHD focused on measuring 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

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Massachusetts General HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Regimen 1: Fludarabine, Cyclophosphamide, and TBI

Regimen 2: Fludarabine, Melphalan, and TBI

Arm Description

-. 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

-. 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

Outcomes

Primary Outcome Measures

Number of patients achieving successful donor engraftment
(absolute neutrophil count > 500/uL and ≥ 90% donor cell chimerism)

Secondary Outcome Measures

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%.

Full Information

First Posted
July 13, 2020
Last Updated
September 30, 2021
Sponsor
Zachariah Michael DeFilipp
Collaborators
Regimmune Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT04473911
Brief Title
Haplo Peripheral Blood Sct In GVHD Prevention
Official Title
Reduced Intensity Haploidentical Peripheral Blood Stem Cell Transplantation With Post-transplant Cyclophosphamide and Sirolimus/Mycophenolate Mofetil/RGI-2001 Based GVHD Prevention: a Pilot Study
Study Type
Interventional

2. Study Status

Record Verification Date
September 2021
Overall Recruitment Status
Recruiting
Study Start Date
August 14, 2020 (Actual)
Primary Completion Date
December 2022 (Anticipated)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Zachariah Michael DeFilipp
Collaborators
Regimmune Corporation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Regimen 1: Fludarabine, Cyclophosphamide, and TBI
Arm Type
Experimental
Arm Description
-. 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
Arm Title
Regimen 2: Fludarabine, Melphalan, and TBI
Arm Type
Experimental
Arm Description
-. 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
Intervention Type
Drug
Intervention Name(s)
FLUDARABINE
Other Intervention Name(s)
Fludara®
Intervention Description
predetermined dose, intravenously, a predetermined times per cycle Given in both pre stem cell and post stem cell cycles
Intervention Type
Drug
Intervention Name(s)
CYCLOPHOSPHAMIDE
Other Intervention Name(s)
Cytoxan®, Neosar®
Intervention Description
◦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
Intervention Type
Radiation
Intervention Name(s)
TBI
Intervention Description
Total body irradiation (TBI) once per cycle.
Intervention Type
Drug
Intervention Name(s)
Melphalan
Other Intervention Name(s)
Alkeran®, L-PAM, L-Sarcolysin, Phenylalanine Mustard
Intervention Description
Melphalan, infusion, determined dosage, once per cycle
Intervention Type
Drug
Intervention Name(s)
Sirolimus
Other Intervention Name(s)
Rapamune
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Mycophenolate mofetil
Other Intervention Name(s)
CellCept, Myfortic
Intervention Description
◦Mycophenolate mofetil, oral or iv(predetermined dose or IV TID (based upon actual body weight), at predetermined times per cycle
Intervention Type
Drug
Intervention Name(s)
RGI-2001
Intervention Description
IV, predetermined dose, weekly to 6 total doses
Intervention Type
Drug
Intervention Name(s)
CYCLOPHOSPHAMIDE
Other Intervention Name(s)
Cytoxan®, Neosar®
Intervention Description
◦Given in Post Stem Cell cycle of Regimen #1 and #2 Cyclophosphamide predetermined dose, predetermined number of times in cycle, intravenous infusion
Primary Outcome Measure Information:
Title
Number of patients achieving successful donor engraftment
Description
(absolute neutrophil count > 500/uL and ≥ 90% donor cell chimerism)
Time Frame
60 Days
Secondary Outcome Measure Information:
Title
100-day non-relapse mortality (NRM) rate.
Description
The regimen will be considered as safe if 100d NRM rate is <=5%, and not safe if 100d NRM rate is ≥25%.
Time Frame
100 Days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zachariah DeFilipp, MD
Phone
(617) 726-5765
Email
zdefilipp@mgh.harvard.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zachariah DeFilipp, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zachariah DeFilipp, MD
Phone
617-726-5765
First Name & Middle Initial & Last Name & Degree
Zachariah DeFilipp, MD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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

Learn more about this trial

Haplo Peripheral Blood Sct In GVHD Prevention

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