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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

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

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

NCT ID

NCT04473911

First Posted

July 13, 2020

Last Updated

September 30, 2021

Sponsor

Zachariah Michael DeFilipp

Collaborators

Regimmune Corporation

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

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

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

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

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

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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