Cryopreserved MMUD BM With PTCy for Hematologic Malignancies

Ossium Health

Status and phase: Withdrawn; Phase 1

Conditions: Acute Biphenotypic Leukemia; Acute Leukemia; Acute Lymphocytic Leukemia; Acute Undifferentiated Leukemia; T-lymphoblastic Lymphoma; Myelodysplastic Syndromes; Acute Myeloid Leukemia

Treatments: Drug: Fludarabine; Drug: Mesna; Drug: Cyclophosphamide; Radiation: Total Body Irradiation; Drug: Filgrastim; Procedure: Bone Marrow Transplant; Drug: Mycophenolate Mofetil; Drug: Busulfan; Drug: Sirolimus

Study type: Interventional

Funder types: NETWORK; Industry

Identifiers

NCT05170828

PRESERVE

Details and patient eligibility

About

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.

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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0 participants in 3 patient groups

Regmin A (RIC)

Other group

Description:

Pre-transplant conditioning treatment with Fludarabine, Cyclophosphamide, and Total Body Irradiation (TBI)

Treatment:

Drug: Mycophenolate Mofetil

Drug: Sirolimus

Procedure: Bone Marrow Transplant

Drug: Cyclophosphamide

Drug: Filgrastim

Radiation: Total Body Irradiation

Drug: Cyclophosphamide

Drug: Mesna

Drug: Fludarabine

Regimen B (FIC)

Other group

Description:

Pre-transplant conditioning treatment with Busulfan and Cyclophosphamide OR Fludarabine

Treatment:

Drug: Busulfan

Drug: Mycophenolate Mofetil

Drug: Sirolimus

Procedure: Bone Marrow Transplant

Drug: Cyclophosphamide

Drug: Filgrastim

Drug: Cyclophosphamide

Drug: Mesna

Drug: Fludarabine

Regimen C (FIC)

Other group

Description:

Pre-transplant conditioning treatment with Cyclophosphamide and Total Body Irradiation (TBI)

Treatment:

Drug: Mycophenolate Mofetil

Drug: Sirolimus

Procedure: Bone Marrow Transplant

Drug: Cyclophosphamide

Drug: Filgrastim

Radiation: Total Body Irradiation

Drug: Cyclophosphamide

Drug: Mesna