Donor Stem Cell Transplantation Using α/β+ T-lymphocyte Depleted Grafts From HLA Mismatched Donors
Status and phase
Conditions
Treatments
Details and patient eligibility
About
This study is being done to learn whether a new method to prevent rejection between the donor immune system and the patient's body is effective.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
Subject Inclusion Criteria:
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Patients with any of the following hematologic malignancies who are considered to be eligible for allogeneic transplantation:
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Acute lymphoid leukemia (ALL) in first complete remission (CR1) with high risk for relapse including:
- Detectable minimal residual disease by either multicolor flow cytometry or by genomic assay after initial induction therapy
- t(9;22) or detected BCR-ABL1 translocation by genomic methodologies
- BCR-ABL1-Like B-ALL [23] including mutations of IKZF1 or CRLF2
- Translocations or mutations involving 11q23 (MLL) gene.
- Hypodiploid karyotype
- Deletion of 9p
- Loss of 17p or TP53 mutation
- T-lymphocyte lineage antigen expression (T-ALL)
- Prior CNS or other extramedullary involvement
- WBC count ≥ 100,000 cells/μL at diagnosis
- Acute biphenotypic or bilineal leukemia in CR1
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Acute myeloid leukemia (AML) in CR1 with
- Detectable minimal residual disease (MRD) by either multicolor flow cytometry or by genomic assay after initial induction therapy
- In the absence of MRD any intermediate or high risk features according to the European LeukemiaNet 2017 guidelines indlucing:
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Mutated FL T3-ITD or FL T3-TKD
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Cytogenetic abnormalities not classified as favorable
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Cytogenetic abnormalities associated with myelodysplastic syndrome including abnormalities of chromosome 5, 7, or 17p
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Complex karyotype or monosomal karyotype
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t(9;11)(p21.1;q23.3); MLL-KMT2A or other rearrangements of KMT2A
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t(9;11); BCR-ABL1
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Inversions or translocations of chromosome 3
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T(6;9)(p23;q34.1); DEK-NUP214
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Somatic mutation of RUNX1, ASX1 or TP53
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Extramedullary involvement
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WBC count ≥100,000 cells/μL at diagnosis
- Relapsed acute leukemia with ≤ 5% blasts in the bone marrow prior to transplantation (i.e. CR2 or greater).
- Myelodysplastic syndrome, myeloproliferative neoplasms, or MDS/MPN overlap syndrome with ≤ 10% blasts and at least one of the following:
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Revised International Prognostic Scoring System risk score of INT, HIGH, or VERY HIGH at the time of transplant evaluation.
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Life-threatening cytopenias
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Karyotype or genomic changes that indicate high risk for progression to acute myelogenous leukemia, including abnormalities of chromosome 7 or 3, mutations of TP53, or complex or monosomal karyotype.
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Therapy related disease or disease evolving from other malignant processes.
- Chronic myelomonocytic leukemia (CMML) with ≤ 10% blasts prior to transplantation.
- Chronic myeloid leukemia (CML) meeting one of the following criteria:
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Failed or are intolerant to BCR-ABL tyrosine kinase inhibitors.
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CML with BCR-ABL mutation consistent with poor response to tyrosine kinase inhibition (e.g. T351I mutation).
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CML with accelerated or blast phase with <10% blasts after therapy.
- Chronic lymphocytic leukemia (CLL) with high risk disease as defined by the EBMT consensus criteria
- Hodgkin lymphoma meeting both of the following criteria:
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Responding to therapy prior to enrollment
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Relapse after autologous bone marrow transplant or are ineligible for autologous bone marrow transplant.
°Non-Hodgkin lymphoma meeting both of the following criteria:
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Responding to therapy prior to enrollment.
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Relapse after prior autologous bone marrow transplant or are ineligible for autologous bone marrow transplant.
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Patients aged from birth through 65 years old are eligible.
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Patients must have Karnofsky/Lanksy performance status ≥70%.
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Cardiac left ventricular ejection fraction ≥50% at rest.
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Serum bilirubin ≤ 2 mg/dL. Patients with Gilbert's disease or ongoing hemolytic anemia are acceptable if the direct bilirubin is ≤ 2 mg/dL.
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AST and ALT ≤ 2.5 x ULN unless thought to be disease related
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Estimated or measured creatinine clearance > 50 mL/min/1.73 m^2 body surface area.
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Adult patients and pediatric patients capable of performing pulmonary function studies must have hemoglobin adjusted pulmonary DLCO ≥50% of predicted.
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Subject Exclusion Criteria:
- Persons with a HLA matched sibling donor or a 8/8 allele level HLA-matched unrelated donor.
- Female patients who are pregnant or breast-feeding.
- Persons with an infection that is not responding to antimicrobial therapy.
- Persons who are seropositive for HIV.
- Persons with active/detectable central nervous system malignancy.
- Persons who do not meet the age and organ function criteria specified above.
- Presence of psychiatric or neurologic disease, or lack of social support that limits the patient's ability to comply with the treatment protocol including supportive care, followup, and research tests.
- Prior allogeneic hematopoietic cell transplantation are ineligible.
- Patients with history of other malignancy within 5 years of study therapy are ineligible with the following exceptions: Low grade prostate cancer (Gleason's ≤6) treated with curative intent, breast ductal carcinoma in situ treated with curative intent, or nonmelanomatous skin carcinomas.
Donor Inclusion and Exclusion Criteria:
- Partially HLA-matched unrelated volunteers (allele level matched at 6-7 of 8 HLA loci: -A, -B, -C, and -DRB1) are eligible.
- Related, haploidentical donors are eligible.
- Able to provide informed consent to the donation process
- Meet standard criteria for donor collection as defined by the National Marrow Donor Program Guidelines.
Trial design
Primary purpose
Allocation
Interventional model
Masking
9 participants in 3 patient groups
Trial contacts and locations
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Data sourced from clinicaltrials.gov
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