A Multi-Center, Phase II Trial of HLA-Mismatched Unrelated Donor Hematopoietic Cell Transplantation With Post-Transplantation Cyclophosphamide for Patients With Hematologic Malignancies

Who is this study for? Patients with hematologic malignancies
What treatments are being studied? HLA-Mismatched Unrelated Donor Hematopoietic Cell Transplantation+Post-Transplantation Cyclophosphamide
Status: Recruiting
Location: See all (34) locations...
Intervention Type: Procedure, Radiation, Drug, Other
Study Type: Interventional
Study Phase: Phase 2
SUMMARY

This is a prospective, multi-center, Phase II study of hematopoietic cell transplantation (HCT) using human leukocyte antigen (HLA)-mismatched unrelated donors (MMUD) for peripheral blood stem cell transplant in adults and bone marrow stem cell transplant in children. Post-transplant cyclophosphamide (PTCy), tacrolimus and mycophenolate mofetil (MMF) will be used for for graft versus host disease (GVHD) prophylaxis. This trial will study how well this treatment works in patients with hematologic malignancies.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 1
Healthy Volunteers: No
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

• Planned MAC regimen as defined per protocol

• Available partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with age < 35 years

• Product planned for infusion is PBSC

• HCT Comorbidity Index (HCT-CI) < 5

• 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 myelodysplastic syndrome (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 multigated acquisition scan (MUGA) results

• Estimated creatinine clearance > 60 mL/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 results

• Liver function acceptable per local institutional guidelines

• Karnofsky performance status (KPS) of > 70%

• Subjects ≥ 18 years of age or legally authorized representative must have the ability to give informed consent according to applicable regulatory and local institutional requirements.

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

• Planned NMA/RIC regimen as defined per protocol

• Available partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with age < 35 years

• Product planned for infusion is PBSC

• 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

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

• Cardiac function: Left ventricular ejection fraction > 45% based on most recent echocardiogram or MUGA results with no clinical evidence of heart failure

• Estimated creatinine clearance > 60 mL/min calculated by equation

• Pulmonary function: DLCO corrected for hemoglobin > 50% and FEV1 predicted > 50% based on most recent pulmonary function test results

• Liver function acceptable per local institutional guidelines

• KPS of > 60%

• Subjects ≥ 18 years of age or legally authorized representative must have the ability to give informed consent according to applicable regulatory and local institutional requirements.

• Age > 1 years and < 21 years at the time of signing informed consent

• Partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with age < 35 years

• Product planned for infusion is BM

• Planned MAC regimen as defined per protocol

• One of the following diagnosis:

• AML in 1st remission or beyond with ≤ 5% marrow blasts, no circulating blasts or evidence of extra-medullary disease. Pre-transplant MRD testing will be performed as per standard of practice at the treating institution. Patients with any MRD status are eligible and should be enrolled at the discretion of provider. Documentation of bone marrow assessment will be accepted within 45 days prior to the anticipated start of conditioning.

• Patients MDS with no circulating blasts and less than 10% blasts in the bone marrow. Documentation of bone marrow assessment will be accepted within 45 days prior to the anticipated start of conditioning.

• ALL in 1st remission or beyond with ≤ 5% marrow blasts, no circulating blasts, or evidence of extra-medullary disease. Pre-transplant MRD testing will be performed as standard practice at the treating institution with the goal of achieving MRD of <0.01%. Patients with any MRD status are eligible and should be enrolled at the discretion of provider. Documentation of bone marrow assessment will be accepted within 45 days prior to the anticipated start of conditioning.

• Other leukemia (mixed-phenotype acute leukemia [MPAL], CML, or other leukemia) in morphologic remission with ≤ 5% marrow blasts and no circulating blasts or evidence of extramedullary disease. Documentation of bone marrow assessment will be accepted within 45 days prior to the anticipated start of conditioning.

• Chemotherapy sensitive lymphoma in at least partial remission (PR)

• KPS or Lansky performance score ≥ 70%

• Cardiac function: Left ventricular ejection fraction of ≥ 50% and shortening fraction of ≥ 27% based on most recent echocardiogram

• Glomerular Filtration Rate (GFR) of ≥ 60ml/min/1.73m2 measured by nuclear medicine scan or calculated from a 24 hour urine collection

• Pulmonary function: DLCO corrected for hemoglobin, FEV1, and Forced Vital Capacity (FVC) of ≥50% if able to perform pulmonary function tests. If unable to perform pulmonary function tests, must have a resting pulse oximetry of >92% without supplemental oxygen.

• Hepatic: Total bilirubin ≤ 2.5 mg/dL and alanine aminotransferase (ALT), aspartate aminotransferase (AST) < 3x the upper limit of normal

• Legal guardian permission must be obtained for subjects < 18 years of age. Pediatric subjects will be included in age appropriate discussion in order to obtain assent.

• Subjects ≥ 18 years of age or legally authorized representative must have the ability to give informed consent according to applicable regulatory and local institutional requirements.

• 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, -DRB1, -DQB1, and -DPB1

• Age > 18 years and < 35 years at the time of signing informed consent

• Meet the donor registries' medical suitability requirements for PBSC or BM 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 (or BM for stratum 3)

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

Locations
United States
California
City of Hope National Medical Center
Recruiting
Duarte
Stanford University
Recruiting
Stanford
Colorado
Colorado Blood Cancer Institute
Recruiting
Denver
Florida
University of Florida Health Shands Hospital
Recruiting
Gainesville
University of Miami Sylvester Cancer Center
Recruiting
Miami
H. Lee Moffitt Cancer Center and Research Institute
Recruiting
Tampa
Georgia
Children's Healthcare of Atlanta
Recruiting
Atlanta
Emory University Medical Center
Recruiting
Atlanta
Illinois
Northwestern University
Recruiting
Chicago
The University of Chicago
Recruiting
Chicago
Massachusetts
Dana Farber Cancer Institute
Recruiting
Boston
Maryland
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Recruiting
Baltimore
University of Maryland Medical Center
Recruiting
Baltimore
Michigan
University of Michigan Medical Center - Mott Children's Hospita
Recruiting
Ann Arbor
Karmanos Cancer Institute
Recruiting
Detroit
Minnesota
Mayo Clinic Rochester
Recruiting
Rochester
Missouri
Washington University/Barnes Jewish Hospital
Recruiting
Saint Louis
North Carolina
University of North Carolina Chapel Hill
Recruiting
Chapel Hill
Levine Cancer Institute
Recruiting
Charlotte
New York
Roswell Park Comprehensive Cancer Center
Recruiting
Buffalo
Columbia University Medical Center
Recruiting
New York
Memorial Sloan Kettering Cancer Center
Recruiting
New York
Ohio
Ohio State Medical Center, James Cancer Center
Recruiting
Columbus
Oregon
Oregon Health and Science University
Recruiting
Portland
Pennsylvania
Thomas Jefferson University Sidney Kimmel Cancer Center
Recruiting
Philadelphia
University of Pennsylvania
Recruiting
Philadelphia
Tennessee
TriStar Medical Group Children's Specialists
Recruiting
Nashville
Vanderbilt University Medical Center
Recruiting
Nashville
Texas
St. David's South Austin Medical Center
Recruiting
Austin
Texas Transplant Institute
Recruiting
San Antonio
Virginia
University of Virginia
Recruiting
Charlottesville
Virginia Commonwealth University
Recruiting
Richmond
Wisconsin
University of Wisconsin Hospital and Clinic
Recruiting
Madison
Froedtert & the Medical College of Wisconsin
Recruiting
Milwaukee
Contact Information
Primary
Janelle Olson, PhD
jolson@nmdp.org
763-406-8147
Backup
Erin Leckrone
eleckron@nmdp.org
763-406-5124
Time Frame
Start Date: September 30, 2021
Estimated Completion Date: July 2024
Participants
Target number of participants: 180
Treatments
Experimental: Regimen A (MAC: busulfan and fludarabine, PBSC HCT)
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.
Experimental: Regimen B (MAC: Fludarabine and TBI; PBSC HCT)
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 PBSC graft infusion from a mismatched unrelated donor on Day 0.
Experimental: Regimen C (RIC: Fludarabine and Busulfan; PBSC HCT)
Patients receive:~Fludarabine (120-180 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 PBSC graft infusion from a mismatched unrelated donor on Day 0.
Experimental: Regimen D (RIC: Fludarabine and Melphalan; PBSC HCT)
Patients receive:~Fludarabine (120-180 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.
Experimental: Regimen E (NMA: Fludarabine, Cyclophosphamide, TBI; PBSC HCT)
Patients receive:~Fludarabine (150 mg/m2 total dose) IV on days -6 to -2~Cyclophosphamide (29-50 mg/kg) IV on days -6 and -5~TBI (200 cGy) on day -1~Patients receive a PBSC graft infusion from a mismatched unrelated donor on Day 0.
Experimental: Regimen F (MAC: Busulfan and Cyclophosphamide; BM HCT)
Patients receive:~Busulfan (dosed by age and weight per institutional standards to target goal pharmacokinetic (PK) in range noted in protocol.) on days -6 to -3~Cyclophosphamide (100 mg/kg total dose) IV on days -2 and -1~Patients receive a bone marrow (BM) graft infusion from a mismatched unrelated donor on Day 0.
Experimental: Regimen G (MAC: Cyclophosphamide and TBI; BM HCT)
Patients receive:~Cyclophosphamide (100 mg/kg total dose) IV on days -5 and -4~TBI (1200 cGy total dose) on days -3, -2 and -1~Patients receive a BM graft infusion from a mismatched unrelated donor on Day 0.
Sponsors
Leads: Center for International Blood and Marrow Transplant Research
Collaborators: National Marrow Donor Program

This content was sourced from clinicaltrials.gov

Similar Clinical Trials