Donor Stem Cell Transplantation Using α/β+ T-lymphocyte Depleted Grafts From HLA Mismatched Donors

• Status: Active, not recruiting
• Trial end date: 2023-07-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Memorial Sloan Kettering Cancer Center
• Treatments: Antilymphocyte Serum; Busulfan; Clofarabine; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Melphalan; Rituximab; Thiotepa; Thymoglobulin

Criteria

Subject Inclusion Criteria:

• Patients with any of the following hematologic malignancies who are considered to be eligible for allogeneic transplantation:

• 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

• 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:

• Mutated FL T3-ITD or FL T3-TKD

• Cytogenetic abnormalities not classified as favorable

• Cytogenetic abnormalities associated with myelodysplastic syndrome including abnormalities of chromosome 5, 7, or 17p

• Complex karyotype or monosomal karyotype

• t(9;11)(p21.1;q23.3); MLL-KMT2A or other rearrangements of KMT2A

• t(9;11); BCR-ABL1

• Inversions or translocations of chromosome 3

• T(6;9)(p23;q34.1); DEK-NUP214

• Somatic mutation of RUNX1, ASX1 or TP53

• Extramedullary involvement

• 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:

• Revised International Prognostic Scoring System risk score of INT, HIGH, or VERY HIGH at the time of transplant evaluation.

• Life-threatening cytopenias

• 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.

• 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:

• Failed or are intolerant to BCR-ABL tyrosine kinase inhibitors.

• CML with BCR-ABL mutation consistent with poor response to tyrosine kinase inhibition (e.g. T351I mutation).

• 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:

• Responding to therapy prior to enrollment

• Relapse after autologous bone marrow transplant or are ineligible for autologous bone marrow transplant.

°Non-Hodgkin lymphoma meeting both of the following criteria:

• Responding to therapy prior to enrollment.

• Relapse after prior autologous bone marrow transplant or are ineligible for autologous bone marrow transplant.

• Patients aged from birth through 65 years old are eligible.

• Patients must have Karnofsky/Lanksy performance status ≥70%.

• Cardiac left ventricular ejection fraction ≥50% at rest.

• Serum bilirubin ≤ 2 mg/dL. Patients with Gilbert's disease or ongoing hemolytic anemia are acceptable if the direct bilirubin is ≤ 2 mg/dL.

• AST and ALT ≤ 2.5 x ULN unless thought to be disease related

• Estimated or measured creatinine clearance > 50 mL/min/1.73 m^2 body surface area.

• Adult patients and pediatric patients capable of performing pulmonary function studies must have hemoglobin adjusted pulmonary DLCO ≥50% of predicted.

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.