A Phase II Study of Reduced Dose Post Transplantation Cyclophosphamide as GvHD Prophylaxis in Adult Patients With Hematologic Malignancies Receiving HLA-Mismatched Unrelated Donor Peripheral Blood Stem Cell Transplantation

Status: Recruiting
Location: See all (32) locations...
Intervention Type: Other, Radiation, Drug, Procedure
Study Type: Interventional
Study Phase: Phase 2
SUMMARY

The goal of this clinical trial is to determine the effectiveness of Reduced Dose Post-Transplant Cyclophosphamide (PTCy) in patients with hematologic malignancies after receiving an HLA-Mismatched Unrelated Donor (MMUD) . The main question\[s\] it aims to answer are: * Does a reduced dose of PTCy reduce the occurrence of infections in the first 100 days after transplant? * Does a reduced dose of PTCy maintain the same level of protection against Graft Versus Host Disease (GvHD) as the standard dose of PTCy?

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• Age ≥ 18 years and \< 66 years (chemotherapy-based conditioning) or \< 61 years (total body irradiation \[TBI\]-based conditioning) at the time of signing informed consent

• Patient or legally authorized representative has the ability to provide informed consent according to the applicable regulatory and institutional requirements.

• Stated willingness to comply with all study procedures and availability for the duration of the study.

• Planned MAC regimen as defined per study protocol

• Available partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with age ≥ 18 and ≤ 40 years (≤ 35 preferred).

• Product planned for infusion is MMUD T-cell replete PBSC allograft

• HCT-CI \< 5. The presence of prior malignancy will not be used to calculate HCT-CI for this trial to allow for the inclusion of patients with secondary or therapy-related AML or MDS.

• One of the following diagnoses:

∙ Acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or other acute leukemia in 1st remission or beyond with ≤ 5% marrow blasts and no circulating blasts or evidence of extra-medullary disease. Documentation of bone marrow assessment will be accepted within 45 days prior to the anticipated start of conditioning.

‣ Patients with MDS with no circulating blasts and with \< 10% blasts in the bone marrow (higher blast percentage allowed in MDS due to lack of differences in outcomes with \< 5% or 5-10% blasts in MDS). Documentation of bone marrow assessment will be accepted within 45 days prior to the anticipated start of conditioning.

• Cardiac function: Left ventricular ejection fraction ≥ 45% based on most recent echocardiogram or multi-gated acquisition scan (MUGA) results.

⁃ Estimated creatinine clearance ≥ 45mL/min calculated by equation.

⁃ Pulmonary function: diffusing capacity of the lungs for carbon monoxide (DLCO) corrected for hemoglobin \> 50% and forced expiratory volume in first second (FEV1) predicted \> 50% based on most recent pulmonary function test (PFT) results

⁃ Liver function acceptable per local institutional guidelines

⁃ KPS of ≥ 70%

• Age ≥18 years at the time of signing informed consent

• Patient or legally authorized representative has the ability to provide informed consent according to the applicable regulatory and local institutional requirements.

• Stated willingness to comply with all study procedures and availability for the duration of the study.

• Planned NMA/RIC regimen per study protocol

• Available partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with age ≥ 18 and ≤ 40 years (≤ 35 preferred).

• Product planned for infusion is MMUD T-cell replete PBSC allograft

• One of the following diagnoses:

∙ Patients with acute leukemia or chronic myeloid leukemia (CML) with no circulating blasts, no evidence of extramedullary disease, and with \< 5% blasts in the bone marrow.

∙ Documentation of bone marrow assessment will be accepted within 45 days prior to the anticipated start of conditioning.

‣ Patients with MDS with no circulating blasts and with \< 10% blasts in the bone marrow (higher blast percentage allowed in MDS due to lack of differences in outcomes with \< 5% or 5-10% blasts in MDS.) Documentation of bone marrow assessment will be accepted within 45 days prior to the anticipated start of conditioning.

‣ Patients with chronic lymphocytic leukemia (CLL) or other leukemias (including prolymphocytic leukemia) with chemosensitive disease at time of transplantation

‣ Higher risk CMML according to CMML-specific prognostic scoring system or high risk MDS/MPN not otherwise specified are eligible, provided there is no evidence of high-grade bone marrow fibrosis or massive splenomegaly at the time of enrollment.

‣ Patients with lymphoma with chemosensitive disease at the time of transplantation

• Cardiac function: Left ventricular ejection fraction ≥ 40% based on most recent echocardiogram or MUGA results with no clinical evidence of heart failure

• Estimated creatinine clearance ≥ 45mL/min calculated by equation

⁃ Pulmonary function: DLCO corrected for hemoglobin \> 50% and FEV1 predicted \>50% based on most recent PFT results

⁃ Liver function acceptable per local institutional guidelines

⁃ KPS of ≥ 60%

• Age ≥18 years at the time of signing informed consent

• Patient or legally authorized representative has the ability to provide informed consent according to the applicable regulatory and local institutional requirements.

• Stated willingness to comply with all study procedures and availability for the duration of the study.

• Planned NMA/RIC regimen per study protocol

• Available partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with age ≥ 18 and ≤ 40 years (≤ 35 preferred).

• Product planned for infusion is MMUD T-cell replete PBSC allograft

• Diagnosis of primary myelofibrosis with risk features making them eligible for HCT. Myelofibrosis secondary to essential thrombocythemia, polycythemia vera, or MDS with grade 4 fibrosis are also eligible. Patients with a myelofibrosis diagnosis require sponsor approval before enrolling.

• Cardiac function: Left ventricular ejection fraction ≥ 40% based on most recent echocardiogram or MUGA results with no clinical evidence of heart failure

• Estimated creatinine clearance ≥ 45 mL/min calculated by equation

⁃ Pulmonary function: DLCO corrected for hemoglobin \> 50% and FEV1 predicted \>50% based on most recent PFT results

⁃ Liver function acceptable per local institutional guidelines

⁃ KPS of ≥ 60%

• Must be unrelated to the subject and high-resolution HLA-matched at 4/8, 5/8, 6/8, or 7/8 (HLA-A, -B, -C, and -DRB1.

• Donor must be typed at high-resolution for a minimum of HLA-A, -B, -C, -DQB1, and -DPB1.

• Age ≥ 18 years and ≤ 40 years at the time of signing informed consent for PBSC donation. Note: donors are preferred to be ≤ 35.

• Meet the donor registries' medical suitability requirements for PBSC donation.

• Must undergo eligibility screening according to current Food and Drug Administration (FDA) requirements. Donors who do not meet one or more of the donor screening requirements may donate under urgent medical need.

• Must agree to donate PBSC.

• Must have the ability to give informed consent according to standard (non-study) informed consent according to applicable donor regulatory requirements.

Locations
United States
Arkansas
University of Arkansas for Medical Sciences
RECRUITING
Little Rock
Arizona
Mayo Clinic Arizona
RECRUITING
Phoenix
Honor Health
RECRUITING
Scottsdale
California
City of Hope
RECRUITING
Duarte
University of California San Francisco
RECRUITING
San Francisco
Stanford University
RECRUITING
Stanford
Colorado
Colorado Blood Cancer Institute at Presbyterian St. Luke's
RECRUITING
Denver
Florida
Mayo Clinic Jacksonville
RECRUITING
Jacksonville
University of Miami Sylvester Cancer Center
RECRUITING
Miami
Moffitt Cancer Center
RECRUITING
Tampa
Georgia
Emory University
RECRUITING
Atlanta
Massachusetts
Dana Farber Cancer Institute
RECRUITING
Boston
Tufts University
RECRUITING
Boston
Maryland
Greenbaum Cancer Center University of Maryland
RECRUITING
Baltimore
Michigan
Karmanos Cancer Institute
RECRUITING
Detroit
Minnesota
University of Minnesota
RECRUITING
Minneapolis
Mayo Clinic
RECRUITING
Rochester
Missouri
Barnes Jewish Hospital / Washington University
RECRUITING
St Louis
North Carolina
University of North Carolina
RECRUITING
Chapel Hill
New York
Memorial Sloan Kettering Cancer Center - Adults
RECRUITING
New York
Ohio
Ohio State Medical Center
RECRUITING
Columbus
Oregon
Oregon Health & Science University
RECRUITING
Portland
Pennsylvania
The Center for Bone Marrow Transplantation at Geisinger
RECRUITING
Danville
Abramson Cancer Center
RECRUITING
Philadelphia
University of Pittsburgh Medical Center
RECRUITING
Pittsburgh
Tennessee
TriStar Centennial
RECRUITING
Nashville
Texas
St. David's South Austin Medical Center
RECRUITING
Austin
MD Anderson Cancer Center
RECRUITING
Houston
Methodist Hospital San Antonio
RECRUITING
San Antonio
Virginia
University of Virginia Health System
RECRUITING
Charlottesville
Washington
Fred Hutchinson Cancer Center
RECRUITING
Seattle
Wisconsin
Froedtert & the Medical College of Wisconsin
RECRUITING
Milwaukee
Contact Information
Primary
Brandan Butler, MBA
bbutler@nmdp.org
763-406-3280
Backup
OPTIMIZE Study Team
OPTIMIZE@NMDP.ORG
Time Frame
Start Date: 2023-12-08
Estimated Completion Date: 2026-06-30
Participants
Target number of participants: 313
Treatments
Experimental: Regimen A (MAC: Busulfan and Fludarabine, PBSC HCT; Reduce Dose PTCy
Patients Receive:~Patients receive:~Busulfan (≥ 9 mg/kg total dose) IV or PO on days -6 to -3 Fludarabine (150 mg/m2 total dose) IV on days -6 to -2~Patients receive a peripheral blood stem cell (PBSC) graft infusion from a mismatched unrelated donor on Day 0.~Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.~First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
Experimental: Regimen B (MAC: Fludarabine and TBI, PBSC HCT; Reduce Dose PTCy
Patients receive:~Fludarabine (90 mg/m2 total dose) IV on days -7 to -5 Total body irradiation (TBI) (1200 cGy total dose) on days -4 to -1~Patients receive a peripheral blood stem cell (PBSC) graft infusion from a mismatched unrelated donor on Day 0.~Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.~First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
Experimental: Regimen C (RIC: Fludarabine and Busulfan; PBSCT HCT; Reduced Dose PTCy
Patients receive:~Fludarabine (150-180 mg/m2 total dose) IV on days -6 to -2 Busulfan (less than or equal to 8 mg/kg PO or 6.4 mg/kg IV) on days -5 and -4~Patients receive a peripheral blood stem cell (PBSC) graft infusion from a mismatched unrelated donor on Day 0.~Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.~First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
Experimental: Regimen D (RIC: Fludarabine and Melphalan; PBSCT HCT; Reduced Dose PTCy
Patients receive:~Fludarabine (125-150 mg/m2 total dose) IV on days -7 to -3 Melphalan (100-140 mg/m2) IV on day -1~Patients receive a PBSC graft infusion from a mismatched unrelated donor on Day 0.~Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.~First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
Experimental: Regimen E (NMA: Fludarabine, Cyclophosphamide, and TBI; PBSCT HCT; Reduced Dose PTCy
Patients receive:~Fludarabine (150mg/m2 total dose) IV on days -6 to -2 Cyclophosphamide (29-50mg/kg) IV on days -6 and -5 TBI (200cGy) on day -1~Patients receive a PBSC graft infusion from a mismatched unrelated donor on Day 0.~Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.~First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
Sponsors
Collaborators: National Marrow Donor Program
Leads: Center for International Blood and Marrow Transplant Research

This content was sourced from clinicaltrials.gov

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