Clinical trial NCT05170828: Cryopreserved MMUD BM With PTCy for Hematologic Malignancies
Official title: PRESERVE: A Multi-Center Trial Using Banked, Cryopreserved HLA-Mismatched Unrelated Donor Bone Marrow and Post-Transplantation Cyclophosphamide in Allogeneic Transplantation for Patients With Hematologic Malignancies
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Acute Leukemia
Myelodysplastic Syndromes
T-lymphoblastic Lymphoma
Acute Lymphocytic Leukemia
Acute Myeloid Leukemia
Acute Biphenotypic Leukemia
Acute Undifferentiated Leukemia
Keywords: Leukemia
MDS
T-LBL
ALL
AML
ABL
AUL
Bone marrow transplant
Lead sponsor: Ossium Health, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Center for International Blood and Marrow Transplant Research
First posted: 2021-12-28
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility 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

Primary outcomes:
measure: Neutrophil engraftment
timeFrame: Day 35 Post HCT
measure: Cumulative incidence and kinetics of neutrophil and platelet recovery
timeFrame: Day 35 Post HCT
measure: Overall survival (OS)
timeFrame: 1-year Post HCT
Secondary outcomes:
measure: Cumulative incidences of aGVHD and cGVHD
timeFrame: 1-year Post HCT
measure: Transplant-related mortality (TRM)
timeFrame: Day 100 and 1-year Post HCT
measure: NK, B- and T-cell immune reconstitution
timeFrame: Days 35, 100, 180, and 1-year Post HCT
measure: Progression free survival (PFS)
timeFrame: 1-year Post HCT
measure: Event free survival (EFS)
timeFrame: 1-year Post HCT
measure: GVHD relapse free survival (GRFS)
timeFrame: 1-year Post HCT
measure: Cumulative incidence of cytokine release syndrome (CRS)
timeFrame: Day 14 Post HCT
measure: Donor chimerism
timeFrame: Days 35, 56, 100, 180, and 1-year Post HCT
measure: Cumulative incidences of viral reactivations and infections
timeFrame: Days 100, 180, and 1-year Post HCT
measure: Cumulative incidence of primary disease relapse/progression
timeFrame: 1-year Post HCT
Other outcomes:
measure: Length of stay in hospital
timeFrame: Day 100 Post HCT
measure: Incidence of clinically-significant infections
timeFrame: 1-year Post HCT
Locations:
Study officials:
affiliation: Center for International Blood and Marrow Transplant Research
name: Jeffery Auletta, MD
role: STUDY_CHAIR
References:
citation: Johnstone BH, Woods JR, Goebel WS, Gu D, Lin CH, Miller HM, Musall KG, Sherry AM, Bailey BJ, Sims E, Sinn AL, Pollok KE, Spellman S, Auletta JJ, Woods EJ. Characterization and Function of Cryopreserved Bone Marrow from Deceased Organ Donors: A Potential Viable Alternative Graft Source. Transplant Cell Ther. 2023 Feb;29(2):95.e1-95.e10. doi: 10.1016/j.jtct.2022.11.010. Epub 2022 Nov 17.