Cryopreserved MMUD BM With PTCy for Hematologic Malignancies

NCT ID: NCT05170828

Last Updated: 2023-11-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE1

Study Classification

INTERVENTIONAL

Study Start Date

2022-09-30

Study Completion Date

2024-11-30

Brief Summary

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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.

Detailed Description

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Conditions

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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Regmin A (RIC)

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

Group Type OTHER

Cyclophosphamide

Intervention Type DRUG

pre-transplant conditioning treatment

Fludarabine

Intervention Type DRUG

pre-transplant conditioning treatment

Total Body Irradiation

Intervention Type RADIATION

pre-transplant conditioning treatment

Mesna

Intervention Type DRUG

given with cyclophosphamide

Sirolimus

Intervention Type DRUG

post-transplant treatment for GVHD

Mycophenolate Mofetil

Intervention Type DRUG

post-transplant treatment for GVHD

Filgrastim

Intervention Type DRUG

post-transplant treatment for GVHD

Cyclophosphamide

Intervention Type DRUG

post-transplant treatment for GVHD

Bone Marrow Transplant

Intervention Type PROCEDURE

Transplant with investigational bone marrow product

Regimen B (FIC)

Pre-transplant conditioning treatment with Busulfan and Cyclophosphamide OR Fludarabine

Group Type OTHER

Cyclophosphamide

Intervention Type DRUG

pre-transplant conditioning treatment

Fludarabine

Intervention Type DRUG

pre-transplant conditioning treatment

Busulfan

Intervention Type DRUG

pre-transplant conditioning treatment

Mesna

Intervention Type DRUG

given with cyclophosphamide

Sirolimus

Intervention Type DRUG

post-transplant treatment for GVHD

Mycophenolate Mofetil

Intervention Type DRUG

post-transplant treatment for GVHD

Filgrastim

Intervention Type DRUG

post-transplant treatment for GVHD

Cyclophosphamide

Intervention Type DRUG

post-transplant treatment for GVHD

Bone Marrow Transplant

Intervention Type PROCEDURE

Transplant with investigational bone marrow product

Regimen C (FIC)

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

Group Type OTHER

Cyclophosphamide

Intervention Type DRUG

pre-transplant conditioning treatment

Total Body Irradiation

Intervention Type RADIATION

pre-transplant conditioning treatment

Mesna

Intervention Type DRUG

given with cyclophosphamide

Sirolimus

Intervention Type DRUG

post-transplant treatment for GVHD

Mycophenolate Mofetil

Intervention Type DRUG

post-transplant treatment for GVHD

Filgrastim

Intervention Type DRUG

post-transplant treatment for GVHD

Cyclophosphamide

Intervention Type DRUG

post-transplant treatment for GVHD

Bone Marrow Transplant

Intervention Type PROCEDURE

Transplant with investigational bone marrow product

Interventions

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Cyclophosphamide

pre-transplant conditioning treatment

Intervention Type DRUG

Fludarabine

pre-transplant conditioning treatment

Intervention Type DRUG

Total Body Irradiation

pre-transplant conditioning treatment

Intervention Type RADIATION

Busulfan

pre-transplant conditioning treatment

Intervention Type DRUG

Mesna

given with cyclophosphamide

Intervention Type DRUG

Sirolimus

post-transplant treatment for GVHD

Intervention Type DRUG

Mycophenolate Mofetil

post-transplant treatment for GVHD

Intervention Type DRUG

Filgrastim

post-transplant treatment for GVHD

Intervention Type DRUG

Cyclophosphamide

post-transplant treatment for GVHD

Intervention Type DRUG

Bone Marrow Transplant

Transplant with investigational bone marrow product

Intervention Type PROCEDURE

Other Intervention Names

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Cytoxan Fludara TBI Busulfelx Mesnex MMF G-CSF Cytoxan Hematopoietic Stem Cell Transplant

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Center for International Blood and Marrow Transplant Research

NETWORK

Sponsor Role collaborator

Ossium Health, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jeffery Auletta, MD

Role: STUDY_CHAIR

Center for International Blood and Marrow Transplant Research

References

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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.

Reference Type DERIVED
PMID: 36402456 (View on PubMed)

Other Identifiers

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PRESERVE

Identifier Type: -

Identifier Source: org_study_id

NCT05068401

Identifier Type: -

Identifier Source: nct_alias

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