Cryopreserved MMUD BM With PTCy for Hematologic Malignancies

• Status: Not yet recruiting
• Trial end date: 2024-11-01
• Target enrollment: 0
• Participant gender: All

Summary

Multicenter single arm study to assess the safety and efficacy of allogeneic transplantation using cryopreserved bone marrow from deceased MMUD and PTCy, sirolimus and MMF for GVHD prophylaxis.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Ossium Health, Inc.
• Collaborator: Center for International Blood and Marrow Transplant Research
• Treatments: Busulfan; Cyclophosphamide; Fludarabine; Mycophenolic Acid; Sirolimus

Criteria

Inclusion Criteria:

• Provision of signed and dated informed consent form

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

• Male or female, aged ≥ 18 and < 71 years (Note: HIV-negative subjects with MDS must be aged <50 at the time of signing the informed consent form)

• Diagnosed with

• Acute leukemias or T-lymphoblastic lymphoma (T-LBL) in 1st or subsequent CR

• Acute lymphocytic leukemia (ALL) or T-LBL as defined by the following:

• < 5% blasts in the bone marrow

• Normal maturation of all cellular components in the bone marrow

• No currently active extramedullary disease (EMD) (e.g., central nervous system (CNS), soft tissue disease)

• ANC ≥ 1,000/mm3

• Acute myeloid leukemia (AML) defined by the following:

• < 5% blasts in the bone marrow

• No blasts with Auer rods

• Normal maturation of all cellular components in the bone marrow

• No currently active EMD (e.g., CNS, soft tissue disease)

• ANC ≥ 1,000/mm3

• Acute biphenotypic leukemia (ABL)/Acute undifferentiated leukemia (AUL) defined by the following:

• < 5% blasts in the bone marrow

• Normal maturation of all cellular components in the bone marrow

• No currently active EMD (e.g., CNS, soft tissue disease)

• ANC ≥ 1,000/mm3

• Myleodysplastic Syndromes (MDS), fulfilling the following criteria:

• Subjects with de novo MDS who have or have previously had Intermediate-2 or High-risk disease as determined by the IPSS. Current Intermediate-2 or High- risk disease is not a requirement

• Subjects must have < 20% bone marrow blasts, assessed within 60 days of informed consent

• Subjects may have received prior therapy for the treatment of MDS prior to enrollment

• Performance status: Karnofsky ≥ 60%

• Adequate organ function defined as:

• Cardiac: LVEF at rest ≥ 35% (RIC cohort) or LVEF at rest ≥ 40% (FIC cohort), or LVFS ≥ 25%

• Pulmonary: DLCO, FEV1, FVC ≥ 50% predicted by pulmonary function tests (PFTs). DLCO value may be corrected or uncorrected for hemoglobin

• Hepatic: total bilirubin ≤ 2.5 mg/dL, and ALT, AST, and ALP < 5 x ULN (unless ALT, AST, and/or ALP are disease related)

• Renal: SCr within normal range for age (see table 5.1B). If SCr is outside normal range for age, CrCl > 40 mL/min/1.73m2 must be obtained (measured by 24-hour (hr) urine specimen or nuclear glomerular filtration rate (GFR), or calculated GFR (by Cockcroft-Gault formula)

• Subjects must have the ability to give informed consent according to applicable regulatory and local institutional requirements

• Availability of deceased HLA MMUD cryopreserved product through Ossium cryobank

• HLA MMUD defined as 4-7/8 HLA-allele matching at MHC class (A, B, or C) or MHC class II (DRB1)

• Additional MHC class II HLA (DP and DQ) typing will be collected, but not incorporated in donor selection

Exclusion Criteria:

• Pediatric patients (17 years or younger)

• Suitable HLA-matched related or 8/8 allele matched (HLA-A, -B, -C, -DRB1) unrelated donor excluding Ossium product

• Autologous HCT < 3 months prior to the time of signing the informed consent form

• Pregnancy or lactation

• Treatment with an investigational drug or other interventional GVHD clinical trials

• Current uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of progression of clinical symptoms or radiologic findings)

• Prior allogeneic HCT

• Primary myelofibrosis or myelofibrosis secondary to essential thrombocythemia or polycythemia vera

• Subjects with MDS may not receive RIC and must be < 50 years of age at the time of signing the informed consent form

• Any condition(s) or diagnosis, both physical or psychological, or physical exam finding that in the investigator's opinion precludes participation