A First-in-Human Study of HLA-Partially to Fully Matched Allogenic Cryopreserved Deceased Donor Bone Marrow Transplantation for Patients With Hematologic Malignancies

Acute Myeloid Leukemia Clinical Trial

Official title:

A First-in-Human Study of HLA-Partially to Fully Matched Allogenic Cryopreserved Deceased Donor Bone Marrow Transplantation for Patients With Hematologic Malignancies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05589896
• Other study ID #: PRESERVE I
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 30, 2024
• Est. completion date: August 2025

Study information

• Verified date: February 2024
• Source: Ossium Health, Inc.
• Contact: Matthew Flores
• Phone: (763)406-3060
• Email: PRESERVE[@]nmdp.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical trial is to determine the safety and feasibility of allogeneic transplantation with bone marrow from a deceased donor in patients with acute leukemias. Patients will either receive myeloablative conditioning or reduced intensity conditioning regimen prior to the transplant. Patients will be followed for 56 days for safety endpoints and remain in follow-up for one year.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: August 2025
• Est. primary completion date: August 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Patient has the ability to provide informed consent according to the applicable regulatory and local institutional requirements

• Male or female, aged =18 and <55 years for patients receiving MAC (Regimen A or Regimen B); aged =18 and <70 years for patients receiving RIC (Regimen C in Cohort 2 only)

• Patient must require allogeneic HCT per the discretion of the treating physician

• Patient must be high-resolution, HLA partially or fully matched (4-8/8 allele matched at HLA-A, -B, -C, DRB1) to an available Ossium HPC, Marrow product

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

• Diagnosed with acute leukemia [acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), acute biophenotypic leukemia (ABL), or acute undifferentiated leukemia (AUL)] in the first remission or beyond with =5% marrow blasts and no circulating blasts or extra-medullary disease documented by bone marrow assessment within 42 days prior to anticipated start of conditioning

• Karnofsky performance status score =70% (MAC) or =60% (RIC)

• HCT comorbidity index (HCT-CI) <5

• Adequate organ function defined as:

1. Cardiac: LVEF at rest =45% (RIC) or LVEF at rest =40% (MAC)

2. Pulmonary: DLCO, FEV1, FVC =50% predicted by pulmonary function tests (PFTs). DLCO value may be corrected for hemoglobin.

3. Hepatic: total bilirubin =2.0 mg/dL, and ALT, AST, and ALP <3 x upper limit normal (ULN), unless ALT, AST, and/or ALP are disease related

4. Renal: SCr within 1.5x normal range for age. If SCr is outside normal range for age, CrCl> 60 mL/min/1.73m2 must be obtained (measured by 24-hour urine specimen or nuclear glomerular filtration rate (GFR), or calculated GFR (by Cockcroft-Gault formula))

Exclusion Criteria:

• Availability of suitable graft from living donor (defined as 7/8 or 8/8 HLA-matched related or unrelated donors, haploidentical donors, or cord blood donors)

• Prior autologous or allogeneic HCT

• Pregnancy or lactation

• Ongoing treatment with an investigational drug used for disease-related treatment within 5 half-lives of the drug

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

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

Related Conditions & MeSH terms

• Acute Biphenotypic Leukemia
• Acute Leukemia
• Acute Lymphoblastic Leukemia
• Acute Myeloid Leukemia
• Acute Undifferentiated Leukemia
• Hematologic Neoplasms
• Leukemia
• Leukemia, Biphenotypic, Acute
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Other:
• Ossium HPC Marrow, Bone Marrow Transplant
Hematopoetic Cell Transplantation
• Pre-transplant conditioning - Myeloablative (MAC)
Regimen A or Regimen B
• Pre-transplant conditioning - Reduced Intensity (RIC)
Regimen C
• Post-transplant treatment
Post-transplant treatment

Locations

Country	Name	City	State
United States	St. David's South Austin Medical Center	Austin	Texas
United States	TriStar Bone Marrow Transplant	Nashville	Tennessee
United States	Columbia University - Herbert Irving Comprehensive Cancer Center	New York	New York
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Ossium Health, Inc.	Center for International Blood and Marrow Transplant Research

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Length of Stay in Hospital	Cumulative days alive and out of the hospital in the first 100 days and in the first year post-transplant.	Day 100 and Day 365
Other	Time to provide Ossium product to the patient from product availability request	Time from preliminary search to find a donor match in the Ossium registry and the time to provide Ossium HPC, Marrow product to recipient (time from donor availability request to delivery of product to transplant center).	Day 365
Primary	Neutrophil Engraftment	Neutrophil engraftment is defined as achieving an absolute neutrophil count (ANC) of greater than or equal to 500/µL for 3 consecutive measurements on 3 different days by Day 28.	Day 28
Primary	Serious Adverse Events	Occurrence of any event classified as SAE. The time of occurrence of each serious adverse event will be recorded.	Day 56
Primary	CTCAE Grade 3/4 Adverse Events (AEs)	Occurrence of any event classified as grade 3/4 AE attributed to Ossium HPC, Marrow per the CTCAE v5.0 guidelines. The time of the occurrence of each event will be recorded.	Day 56
Primary	CTCAE Grade 3/4 Adverse Events (AEs)	Occurrence of any event classified as grade 3 or higher attributed to Ossium HPC, Marrow per the CTCAE v5.0 guidelines as defined in Section 8.5. The time of the occurrence will be recorded.	Day 28
Primary	Death	The time of death will be recorded for each expired patient.	Day 56
Secondary	Cumulative incidences of neutrophil engraftment	Neutrophil engraftment in defined as achieving an absolute neutrophil count (ANC) of greater than or equal to 500/µL for 3 consecutive measurements on different days by Day 28.	Day 28
Secondary	Cumulative incidences of platelet recovery	Platelet recovery is defined as platelets greater than or equal to 20,000/µL for 3 consecutive days in the absence of transfusion for 7 consecutive days by Day 56.	Day 56
Secondary	Cumulative incidence of disease relapses	The cumulative incidence of relapse is measured from the date of transplant (Day 0) until the date of relapse or progression; patients not known to have relapsed are censored on the date they were last examined; patients who died without relapse are counted as a competing cause of failure.	Day 365
Secondary	Transplant-related mortality (TRM)	TRM is defined as death without evidence of disease progression or recurrence.	Day 100 and Day 365
Secondary	Cumulative incidences of acute (aGVHD) Graft Versus Host Disease	aGVHD is defined as any skin, gastrointestinal or liver abnormalities fulfilling the criteria of grades II-IV or grades III-IV.	Day 100, Day 180, and Day 365
Secondary	Cumulative incidences of chronic (cGVHD) Graft Versus Host Disease	cGVHD is defined per National Institutes of Health (NIH) Consensus Criteria and includes organ involvement and severity, and overall global composite score (mild/moderate/severe).	Day 100, Day 180, and Day 365
Secondary	Incidence of clinically-significant infections	A clinically significant infection is defined as any microbiologic or radiographic infection for which antimicrobial therapy was administered.	Day 100 and Day 365