Cryopreserved MMUD BM With PTCy for Hematologic Malignancies

NCT05170828 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: PRESERVE
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

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

Keywords

Leukemia; MDS; T-LBL; ALL; AML; ABL; AUL; Bone marrow transplant

Outcome Measures

Primary Outcomes (3)

• Neutrophil engraftment

  Run-in safety phase primary endpoint; Neutrophil engraftment is defined as neutrophil recovery by Day 35. Neutrophil recovery is defined as donor-derived absolute neutrophil count (ANC) ≥ 500/mm3 for three consecutive days with evidence of donor chimerism in bone marrow or peripheral blood. Full donor chimerism is \>95%, and mixed donor chimerism is defined as 5-95%.

  Day 35 Post HCT

• Cumulative incidence and kinetics of neutrophil and platelet recovery

  Main phase primary endpoint; Neutrophil recovery is defined as achieving an absolute neutrophil count (ANC) greater than or equal to 500/mm3 for three consecutive measurements on three different days. The first of the three days will be designated the day of neutrophil recovery. The competing event is death without neutrophil recovery. For subjects who never drop ANC below 500/mm3, the date of neutrophil recovery will be Day 1 post-transplant. Platelet recovery is defined by two different metrics: the first day of a sustained platelet count greater than or equal to 20,000/mm3 or greater than or equal to 50,000/mm3 with no platelet transfusions in the preceding seven days. The first day of sustained platelet count above these thresholds will be designated the day of platelet engraftment. For subjects who never drop their platelet count below 20,000/mm3, the date of platelet recovery will be Day 1 post HCT.

  Day 35 Post HCT

• Overall survival (OS)

  Main phase primary endpoint; The primary endpoint for the study is OS at 1-year post-HCT. The event is death from any cause. The time to this event is the time from HCT to death, loss to follow-up, or end of study (whichever comes first). Subjects who are lost to follow-up prior to 1-year will be censored at the time of the last observation, and the OS probability will be estimated using the Kaplan-Meier method.

  1-year Post HCT

Secondary Outcomes (10)

• Cumulative incidences of aGVHD and cGVHD

  1-year Post HCT

• Transplant-related mortality (TRM)

  Day 100 and 1-year Post HCT

• NK, B- and T-cell immune reconstitution

  Days 35, 100, 180, and 1-year Post HCT

• Progression free survival (PFS)

  1-year Post HCT

• Event free survival (EFS)

  1-year Post HCT

Other Outcomes (2)

• Length of stay in hospital

  Day 100 Post HCT

• Incidence of clinically-significant infections

  1-year Post HCT

Study Arms (3)

Regmin A (RIC)

OTHER

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

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

Regimen B (FIC)

OTHER

Pre-transplant conditioning treatment with Busulfan and Cyclophosphamide OR Fludarabine

Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Busulfan; Drug: Mesna; Drug: Sirolimus; Drug: Mycophenolate Mofetil; Drug: Filgrastim; Procedure: Bone Marrow Transplant

Regimen C (FIC)

OTHER

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

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

Interventions

Cyclophosphamide DRUG

pre-transplant conditioning treatment

Also known as: Cytoxan

Regimen B (FIC); Regimen C (FIC); Regmin A (RIC)

Fludarabine DRUG

pre-transplant conditioning treatment

Also known as: Fludara

Regimen B (FIC); Regmin A (RIC)

Total Body Irradiation RADIATION

pre-transplant conditioning treatment

Also known as: TBI

Regimen C (FIC); Regmin A (RIC)

Busulfan DRUG

pre-transplant conditioning treatment

Also known as: Busulfelx

Regimen B (FIC)

Mesna DRUG

given with cyclophosphamide

Also known as: Mesnex

Regimen B (FIC); Regimen C (FIC); Regmin A (RIC)

Sirolimus DRUG

post-transplant treatment for GVHD

Regimen B (FIC); Regimen C (FIC); Regmin A (RIC)

Mycophenolate Mofetil DRUG

post-transplant treatment for GVHD

Also known as: MMF

Regimen B (FIC); Regimen C (FIC); Regmin A (RIC)

Filgrastim DRUG

post-transplant treatment for GVHD

Also known as: G-CSF

Regimen B (FIC); Regimen C (FIC); Regmin A (RIC)

Bone Marrow Transplant PROCEDURE

Transplant with investigational bone marrow product

Also known as: Hematopoietic Stem Cell Transplant

Regimen B (FIC); Regimen C (FIC); Regmin A (RIC)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Ossium Health, Inc.: lead

Related Publications (1)

• 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.

  PMID: 36402456 DERIVED

MeSH Terms

Conditions

Myelodysplastic Syndromes; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Leukemia, Biphenotypic, Acute; Leukemia

Interventions

Cyclophosphamide; fludarabine; fludarabine phosphate; Whole-Body Irradiation; Busulfan; Mesna; Sirolimus; Mycophenolic Acid; Filgrastim; Granulocyte Colony-Stimulating Factor; Bone Marrow Transplantation; Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Radiotherapy; Therapeutics; Investigative Techniques; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Sulfhydryl Compounds; Macrolides; Lactones; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Tissue Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Transplantation; Surgical Procedures, Operative; Cell Transplantation

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2021
• First Posted: December 28, 2021
• Study Start: September 1, 2022
• Primary Completion: March 1, 2024
• Study Completion: November 1, 2024
• Last Updated: February 24, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share