ACTIVE_NOT_RECRUITING

HLA-Mismatched Unrelated Donor Hematopoietic Cell Transplantation With Post-Transplantation Cyclophosphamide

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2021-09-30

Study Completion:2025-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT04904588

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:1 Year

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. 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 2. Planned MAC regimen as defined per protocol 3. Available partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with age \< 35 years 4. Product planned for infusion is PBSC 5. HCT Comorbidity Index (HCT-CI) \< 5 6. One of the following diagnoses: 1. 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. 2. 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. 7. Cardiac function: Left ventricular ejection fraction \> 45% based on most recent echocardiogram or multigated acquisition scan (MUGA) results 8. Estimated creatinine clearance \> 60 mL/min calculated by equation 9. 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 10. Liver function acceptable per local institutional guidelines 11. Karnofsky performance status (KPS) of \> 70% 12. 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. 1. Age \> 18 years at the time of signing informed consent 2. Planned NMA/RIC regimen as defined per protocol 3. Available partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with age \< 35 years 4. Product planned for infusion is PBSC 5. One of the following diagnoses: 1. 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. 2. 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. 3. Patients with chronic lymphocytic leukemia (CLL) or other leukemias (including prolymphocytic leukemia) with chemosensitive disease at time of transplantation 4. Patients with lymphoma with chemosensitive disease at the time of transplantation 6. Cardiac function: Left ventricular ejection fraction \> 45% based on most recent echocardiogram or MUGA results with no clinical evidence of heart failure 7. Estimated creatinine clearance \> 60 mL/min calculated by equation 8. Pulmonary function: DLCO corrected for hemoglobin \> 50% and FEV1 predicted \> 50% based on most recent pulmonary function test results 9. Liver function acceptable per local institutional guidelines 10. KPS of \> 60% 11. 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. 1. Age \> 1 years and \< 21 years at the time of signing informed consent 2. Partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with age \< 35 years 3. Product planned for infusion is BM 4. Planned MAC regimen as defined per protocol 5. One of the following diagnosis: 1. 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. 2. 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. 3. 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. 4. 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. 5. Chemotherapy sensitive lymphoma in at least partial remission (PR) 6. KPS or Lansky performance score ≥ 70% 7. Cardiac function: Left ventricular ejection fraction of ≥ 50% and shortening fraction of ≥ 27% based on most recent echocardiogram 8. Glomerular Filtration Rate (GFR) of ≥ 60ml/min/1.73m2 measured by nuclear medicine scan or calculated from a 24 hour urine collection 9. 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. 10. Hepatic: Total bilirubin ≤ 2.5 mg/dL and alanine aminotransferase (ALT), aspartate aminotransferase (AST) \< 3x the upper limit of normal 11. 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. 12. 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.	1. Donor unwilling or unable to donate 2. Recipient positive anti-donor HLA antibodies against a mismatched HLA in the selected donor determined by the presence of donor specific HLA antibodies (DSA) to any mismatched HLA allele/antigen at any of the following loci (HLA-A, -B, -C, -DRB1, DRB3, DRB4, DRB5, -DQA1, -DQB1, -DPA1, -DPB1) with median fluorescence intensity (MFI) \>3000 by microarray-based single antigen bead testing. In patients receiving red blood cell or platelet transfusions, DSA evaluation must be performed or repeated post-transfusion and prior to donor mobilization and initiation of recipient preparative regimen.

Inclusion Criteria

Exclusion Criteria

1. 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
2. Planned MAC regimen as defined per protocol
3. Available partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with age \< 35 years
4. Product planned for infusion is PBSC
5. HCT Comorbidity Index (HCT-CI) \< 5
6. One of the following diagnoses:
1. 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.
2. 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.
7. Cardiac function: Left ventricular ejection fraction \> 45% based on most recent echocardiogram or multigated acquisition scan (MUGA) results
8. Estimated creatinine clearance \> 60 mL/min calculated by equation
9. 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
10. Liver function acceptable per local institutional guidelines
11. Karnofsky performance status (KPS) of \> 70%
12. 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.
1. Age \> 18 years at the time of signing informed consent
2. Planned NMA/RIC regimen as defined per protocol
3. Available partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with age \< 35 years
4. Product planned for infusion is PBSC
5. One of the following diagnoses:
1. 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.
2. 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.
3. Patients with chronic lymphocytic leukemia (CLL) or other leukemias (including prolymphocytic leukemia) with chemosensitive disease at time of transplantation
4. Patients with lymphoma with chemosensitive disease at the time of transplantation
6. Cardiac function: Left ventricular ejection fraction \> 45% based on most recent echocardiogram or MUGA results with no clinical evidence of heart failure
7. Estimated creatinine clearance \> 60 mL/min calculated by equation
8. Pulmonary function: DLCO corrected for hemoglobin \> 50% and FEV1 predicted \> 50% based on most recent pulmonary function test results
9. Liver function acceptable per local institutional guidelines
10. KPS of \> 60%
11. 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.
1. Age \> 1 years and \< 21 years at the time of signing informed consent
2. Partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with age \< 35 years
3. Product planned for infusion is BM
4. Planned MAC regimen as defined per protocol
5. One of the following diagnosis:
1. 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.
2. 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.
3. 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.
4. 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.
5. Chemotherapy sensitive lymphoma in at least partial remission (PR)
6. KPS or Lansky performance score ≥ 70%
7. Cardiac function: Left ventricular ejection fraction of ≥ 50% and shortening fraction of ≥ 27% based on most recent echocardiogram
8. Glomerular Filtration Rate (GFR) of ≥ 60ml/min/1.73m2 measured by nuclear medicine scan or calculated from a 24 hour urine collection
9. 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.
10. Hepatic: Total bilirubin ≤ 2.5 mg/dL and alanine aminotransferase (ALT), aspartate aminotransferase (AST) \< 3x the upper limit of normal
11. 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.
12. 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.

1. Donor unwilling or unable to donate
2. Recipient positive anti-donor HLA antibodies against a mismatched HLA in the selected donor determined by the presence of donor specific HLA antibodies (DSA) to any mismatched HLA allele/antigen at any of the following loci (HLA-A, -B, -C, -DRB1, DRB3, DRB4, DRB5, -DQA1, -DQB1, -DPA1, -DPB1) with median fluorescence intensity (MFI) \>3000 by microarray-based single antigen bead testing. In patients receiving red blood cell or platelet transfusions, DSA evaluation must be performed or repeated post-transfusion and prior to donor mobilization and initiation of recipient preparative regimen.

Contacts and Locations

Principal Investigator

Steven Devine, MD

PRINCIPAL_INVESTIGATOR

NMDP/Be The Match

Study Locations (Sites)

City of Hope National Medical Center

Duarte, California, 91010

United States

University of California San Francisco

San Francisco, California, 94143

United States

Stanford University

Stanford, California, 94305

United States

Colorado Blood Cancer Institute

Denver, Colorado, 80218

United States

University of Florida Health Shands Hospital

Gainesville, Florida, 32610

United States

University of Miami Sylvester Cancer Center

Miami, Florida, 33136

United States

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612

United States

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322

United States

Emory University Medical Center

Atlanta, Georgia, 30322

United States

Northwestern University

Chicago, Illinois, 60611

United States

The University of Chicago

Chicago, Illinois, 60637

United States

University of Maryland Medical Center

Baltimore, Maryland, 21201

United States

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231

United States

Tufts Medical Center

Boston, Massachusetts, 02111

United States

Dana Farber Cancer Institute

Boston, Massachusetts, 02215

United States

University of Michigan Medical Center - Mott Children's Hospita

Ann Arbor, Michigan, 48109

United States

Karmanos Cancer Institute

Detroit, Michigan, 48201

United States

Mayo Clinic Rochester

Rochester, Minnesota, 55905

United States

Washington University/Barnes Jewish Hospital

St. Louis, Missouri, 63110

United States

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14263

United States

Columbia University Medical Center

New York, New York, 10032

United States

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

United States

University of North Carolina Chapel Hill

Chapel Hill, North Carolina, 27599

United States

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229

United States

Ohio State Medical Center, James Cancer Center

Columbus, Ohio, 43210

United States

Oregon Health and Science University

Portland, Oregon, 97239

United States

University of Pennsylvania

Philadelphia, Pennsylvania, 19104

United States

Thomas Jefferson University Sidney Kimmel Cancer Center

Philadelphia, Pennsylvania, 19107

United States

Medical University of South Carolina

Charleston, South Carolina, 29407

United States

TriStar BMT

Nashville, Tennessee, 37203

United States

TriStar Medical Group Children's Specialists

Nashville, Tennessee, 37203

United States

Vanderbilt University Medical Center

Nashville, Tennessee, 37232

United States

St. David's South Austin Medical Center

Austin, Texas, 78704

United States

-Baylor College of Medicine - Texas Children's Hospital and Houston Methodist

Houston, Texas, 77030

United States

Texas Transplant Institute

San Antonio, Texas, 37203

United States

University of Virginia

Charlottesville, Virginia, 22903

United States

Virginia Commonwealth University

Richmond, Virginia, 23298

United States

University of Wisconsin Hospital and Clinic

Madison, Wisconsin, 53792

United States

Froedtert & the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226

United States

Collaborators and Investigators

Sponsor: Center for International Blood and Marrow Transplant Research

Steven Devine, MD, PRINCIPAL_INVESTIGATOR, NMDP/Be The Match

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-09-30

Study Completion Date2025-12

Study Record Updates

Study Start Date2021-09-30

Study Completion Date2025-12

Terms related to this study

Keywords Provided by Researchers

Lymphoma
Leukemia
Hematologic Diseases
Myelodysplastic Syndromes
Preleukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Myeloid, Acute
Leukemia, Biphenotypic, Acute
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Bone Marrow Diseases
Precancerous Conditions
Leukemia, Lymphoid
Leukemia, B-Cell
Leukemia, Myeloid
Cyclophosphamide
Mesna
Tacrolimus
Busulfan
Fludarabine
Total Body Irradiation
Melphalan
Mycophenolate mofetil
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Hematopoietic Stem Cell Transplantation
Unrelated Donors

Additional Relevant MeSH Terms

Acute Lymphoblastic Leukemia
Acute Myelogenous Leukemia
Mixed Phenotype Acute Leukemia
Acute Leukemia
Myelodysplastic Syndromes
Chronic Myelogenous Leukemia
Chronic Lymphocytic Leukemia
Lymphoma

HLA-Mismatched Unrelated Donor Hematopoietic Cell Transplantation With Post-Transplantation Cyclophosphamide

Conditions

Quick Navigation

Study Overview

Description

Official Title

Quick Facts

Study ID

Participation Criteria

Contacts and Locations

Principal Investigator

Study Locations (Sites)

Collaborators and Investigators

Study Record Dates

Study Registration Dates

Study Record Updates

Terms related to this study

Keywords Provided by Researchers

Additional Relevant MeSH Terms