Back to resultsA First-in-Human Study of HLA-Partially to Fully Matched Allogenic Cryopreserved Deceased Donor Bone Marrow Transplantation for Patients With Hematologic Malignancies
Primary Purpose
Acute Leukemia, Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia
Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Busulfan
Fludarabine
Total Body Irradiation
Cyclophosphamide
Mesna
Bone Marrow Transplant
Cyclophosphamide
Tacrolimus
Mycophenolate Mofetil
Filgrastim
Sponsored by
About this trial
This is an interventional treatment trial for Acute Leukemia focused on measuring Leukemia, Hematologic Diseases, ALL, AML, ABL, AUL, Bone Marrow Transplant
Eligibility Criteria
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:
- Cardiac: LVEF at rest ≥45% (RIC) or LVEF at rest ≥40% (MAC)
- Pulmonary: DLCO, FEV1, FVC ≥50% predicted by pulmonary function tests (PFTs). DLCO value may be corrected for hemoglobin.
- 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
- 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Regimen A (MAC)
Regimen B (MAC)
Regimen C (RIC)
Arm Description
Pre-transplant conditioning treatment with Busulfan and Fludarabine Bone Marrow Transplant with Ossium HPC, Marrow Post-Transplant treatment with Cyclophosphamide, Tacrolimus, Mycophenolate Mofetil, and Filgrastim
Pre-transplant conditioning treatment with Fludarabine and Total Body Irradiation Bone Marrow Transplant with Ossium HPC, Marrow Post-Transplant treatment with Cyclophosphamide, Tacrolimus, Mycophenolate Mofetil, and Filgrastim
Pre-transplant conditioning treatment with Fludarabine, Cyclophosphamide, and Total Body Irradiation Bone Marrow Transplant with Ossium HPC, Marrow Post-Transplant treatment with Cyclophosphamide, Tacrolimus, Mycophenolate Mofetil, and Filgrastim
Outcomes
Primary Outcome Measures
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.
Serious Adverse Events
Occurrence of any event classified as SAE. The time of occurrence of each serious adverse event will be recorded.
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.
CTCAE Grade 3 or higher infusion-related toxicity
Occurrence of any event classified as grade 3 infusion-related toxicity per the CTCAE v5.0 guidelines. The time of the occurrence will be recorded.
Death
The time of death will be recorded for each expired patient.
Secondary Outcome Measures
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.
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.
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.
Transplant-related mortality (TRM)
TRM is defined as death without evidence of disease progression or recurrence.
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.
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).
Incidence of clinically-significant infections
A clinically significant infection is defined as any microbiologic or radiographic infection for which antimicrobial therapy was administered.
Full Information
NCT ID
NCT05589896
First Posted
October 18, 2022
Last Updated
October 18, 2022
Sponsor
Ossium Health, Inc.
Collaborators
Center for International Blood and Marrow Transplant Research
1. Study Identification
Unique Protocol Identification Number
NCT05589896
Brief Title
A First-in-Human Study of HLA-Partially to Fully Matched Allogenic Cryopreserved Deceased Donor Bone Marrow Transplantation for Patients With Hematologic Malignancies
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
March 2023 (Anticipated)
Primary Completion Date
March 2025 (Anticipated)
Study Completion Date
December 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ossium Health, Inc.
Collaborators
Center for International Blood and Marrow Transplant Research
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Leukemia, Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Acute Biphenotypic Leukemia, Acute Undifferentiated Leukemia
Keywords
Leukemia, Hematologic Diseases, ALL, AML, ABL, AUL, Bone Marrow Transplant
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Model Description
All patients will receive Ossium HPC, Marrow product. Study arms will be based on conditioning regimen.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
12 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Regimen A (MAC)
Arm Type
Experimental
Arm Description
Pre-transplant conditioning treatment with Busulfan and Fludarabine
Bone Marrow Transplant with Ossium HPC, Marrow
Post-Transplant treatment with Cyclophosphamide, Tacrolimus, Mycophenolate Mofetil, and Filgrastim
Arm Title
Regimen B (MAC)
Arm Type
Experimental
Arm Description
Pre-transplant conditioning treatment with Fludarabine and Total Body Irradiation
Bone Marrow Transplant with Ossium HPC, Marrow
Post-Transplant treatment with Cyclophosphamide, Tacrolimus, Mycophenolate Mofetil, and Filgrastim
Arm Title
Regimen C (RIC)
Arm Type
Experimental
Arm Description
Pre-transplant conditioning treatment with Fludarabine, Cyclophosphamide, and Total Body Irradiation
Bone Marrow Transplant with Ossium HPC, Marrow
Post-Transplant treatment with Cyclophosphamide, Tacrolimus, Mycophenolate Mofetil, and Filgrastim
Intervention Type
Drug
Intervention Name(s)
Busulfan
Other Intervention Name(s)
Busuflex
Intervention Description
pre-transplant conditioning treatment
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
Fludara
Intervention Description
pre-transplant conditioning treatment
Intervention Type
Radiation
Intervention Name(s)
Total Body Irradiation
Other Intervention Name(s)
TBI
Intervention Description
pre-transplant conditioning treatment
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cytoxan
Intervention Description
pre-transplant conditioning treatment
Intervention Type
Drug
Intervention Name(s)
Mesna
Other Intervention Name(s)
Mesnex
Intervention Description
given with Cyclophosphamide
Intervention Type
Procedure
Intervention Name(s)
Bone Marrow Transplant
Other Intervention Name(s)
Hematopoetic Cell Transplantation
Intervention Description
Bone marrow transplant with Ossium HPC, product
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cytoxan
Intervention Description
post-transplant treatment
Intervention Type
Drug
Intervention Name(s)
Tacrolimus
Intervention Description
post-transplant treatment
Intervention Type
Drug
Intervention Name(s)
Mycophenolate Mofetil
Other Intervention Name(s)
MMF
Intervention Description
post-transplant treatment
Intervention Type
Drug
Intervention Name(s)
Filgrastim
Other Intervention Name(s)
G-CSF
Intervention Description
post-transplant treatment
Primary Outcome Measure Information:
Title
Neutrophil Engraftment
Description
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.
Time Frame
Day 28
Title
Serious Adverse Events
Description
Occurrence of any event classified as SAE. The time of occurrence of each serious adverse event will be recorded.
Time Frame
Day 56
Title
CTCAE Grade 3/4 Adverse Events (AEs)
Description
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.
Time Frame
Day 56
Title
CTCAE Grade 3 or higher infusion-related toxicity
Description
Occurrence of any event classified as grade 3 infusion-related toxicity per the CTCAE v5.0 guidelines. The time of the occurrence will be recorded.
Time Frame
Day 56
Title
Death
Description
The time of death will be recorded for each expired patient.
Time Frame
Day 56
Secondary Outcome Measure Information:
Title
Cumulative incidences of neutrophil engraftment
Description
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.
Time Frame
Day 28
Title
Cumulative incidences of platelet recovery
Description
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.
Time Frame
Day 56
Title
Cumulative incidence of disease relapses
Description
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.
Time Frame
Day 365
Title
Transplant-related mortality (TRM)
Description
TRM is defined as death without evidence of disease progression or recurrence.
Time Frame
Day 100 and Day 365
Title
Cumulative incidences of acute (aGVHD) Graft Versus Host Disease
Description
aGVHD is defined as any skin, gastrointestinal or liver abnormalities fulfilling the criteria of grades II-IV or grades III-IV.
Time Frame
Day 100, Day 180, and Day 365
Title
Cumulative incidences of chronic (cGVHD) Graft Versus Host Disease
Description
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).
Time Frame
Day 100, Day 180, and Day 365
Title
Incidence of clinically-significant infections
Description
A clinically significant infection is defined as any microbiologic or radiographic infection for which antimicrobial therapy was administered.
Time Frame
Day 100 and Day 365
Other Pre-specified Outcome Measures:
Title
Length of Stay in Hospital
Description
Cumulative days alive and out of the hospital in the first 100 days and in the first year post-transplant.
Time Frame
Day 100 and Day 365
Title
Time to provide Ossium product to the patient from product availability request
Description
Time to find a donor 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).
Time Frame
Day 365
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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:
Cardiac: LVEF at rest ≥45% (RIC) or LVEF at rest ≥40% (MAC)
Pulmonary: DLCO, FEV1, FVC ≥50% predicted by pulmonary function tests (PFTs). DLCO value may be corrected for hemoglobin.
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
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Shannon Clark, MS
Phone
(763)406-3060
Email
sclark2@nmdp.org
First Name & Middle Initial & Last Name or Official Title & Degree
Eric Hong
Email
eric.hong@ossiumhealth.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeffery Auletta, MD
Organizational Affiliation
Center for International Blood and Marrow Transplant Research
Official's Role
Study Chair
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A First-in-Human Study of HLA-Partially to Fully Matched Allogenic Cryopreserved Deceased Donor Bone Marrow Transplantation for Patients With Hematologic Malignancies
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