Acute Biphenotypic Leukemia, Acute Leukemia, Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Acute Undifferentiated Leukemia, Chronic Myeloid Leukemia (CML), CLL (Chronic Lymphocytic Leukemia), Cutaneous T Cell Lymphomas (CTCL), Hodgkins Lymphoma, MDS (Myelodysplastic Syndrome), Non-Hodgkin Lymphomas
Conditions
Keywords
Leukemia, Hematologic Diseases, ALL, AML, ABL, AUL, Bone Marrow Transplant, Lymphoma, MDS, CLL, CML
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 and chronic leukemias, myelodysplastic syndrome, and certain lymphomas. 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.
Interventions
OTHEROssium HPC Marrow, Bone Marrow Transplant
Hematopoetic Cell Transplantation
OTHERPre-transplant conditioning - Myeloablative (MAC)
Regimen A or Regimen B
OTHERPre-transplant conditioning - Reduced Intensity (RIC)
Regimen C or Regimen D
OTHERPost-transplant treatment
Post-transplant treatment
Sponsors
Ossium Health, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
All patients will receive Ossium HPC, Marrow product. Study arms will be based on order of enrollment and planned conditioning regimen.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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 ≤65 years for patients receiving MAC (Regimen A or Regimen B); aged ≥18 and ≤75 years for patients receiving RIC (Regimen C or D) * 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 malignant hematologic disease including: 1. Acute leukemia \[acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), acute biophenotypic leukemia (ABL), or acute undifferentiated leukemia (AUL)\], MDS without fibrosis, or chronic leukemia (CLL, CML) in the first remission or beyond with ≤5% marrow blasts documented by bone marrow assessment and no circulating blasts or extra-medullary disease within 42 days prior to anticipated start of conditioning 2. Chemosensitive non-Hodgkin's lymphomas, Hodgkin's lymphoma, or cutaneous T cell lymphomas in the first remission or beyond documented by PET/CT imaging and 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 ≥40% (RIC) or LVEF at rest ≥45% (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)
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Neutrophil Engraftment | Day 28 | 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 | Day 56 | 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) | Day 56 | 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 3/4 Adverse Events (AEs) attributed to infusion of Ossium HPC, Marrow | Day 28 | Occurrence of any event classified as grade 3 or higher attributed to Ossium HPC, Marrow infusion per the CTCAE v5.0 guidelines. The time of the occurrence will be recorded. |
| Death | Day 56 | The time of death will be recorded for each expired patient. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative incidences of neutrophil engraftment | Day 28 | 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 | Day 56 | 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 | Day 365 | 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) | Day 100 and Day 365 | TRM is defined as death without evidence of disease progression or recurrence. |
| Cumulative incidences of acute (aGVHD) Graft Versus Host Disease | Day 100, Day 180, and Day 365 | 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 | Day 100, Day 180, and Day 365 | 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 | Day 100 and Day 365 | A clinically significant infection is defined as any microbiologic or radiographic infection for which antimicrobial therapy was administered. |
Countries
United States
Outcome results
None listed