Study to Characterize Mismatched to Fully HLA-Matched Ossium HPC, Marrow and Living Donor Transplantation in Patients With Hematologic Malignancies

Korábbi kezelés

• Autologous transplant within 6 months
• Prior allogeneic HCT
• Participation with an investigational trial within 3 months of planned transplant (Note: participation in survey studies or standard of care studies maybe allowed after sponsors approval or are part of long term follow up for an interventional trial)
• Recipient of allogeneic CART-T therapy
• Recipient of checkpoint inhibitor in last 3 months
• Current uncontrolled bacterial, viral or fungal infection defined as currently taking medication with evidence of progression of clinical symptoms or radiologic findings
• Presence of donor-specific antibodies. Recipient has positive anti-donor HLA antibodies against a mismatched HLA in the selected donor determined by either:
  • positive crossmatch test of any titer (by complement-dependent cytotoxicity or flow cytometric testing) or
  • presence of donor specific HLA antibodies (DSA) to any mismatched HAS allele/antigen at any of the following loci (HLA-A, -B, -C, -DRB1, -DPA1, -DPB1) with median fluoresce intensity (MFI) >3000 by Luminex single antigen bead based solid phase immunoassay tested prior to SSA request and repeated if transplant is >30 days from prior HLA antibody testing or if patient receives additional blood products/transfusion prior to transplant
  • Patients with donor specific HLA antibodies (DSA) to donor that is reduced post treatment of de-sensitization for DSA

Más betegség

• Myeloproliferative disorders or MDS with grade 3 and higher fibrosis are excluded
• Any condition(s) or diagnosis, both physical or psychological, or physical exam finding that in the investigator's opinion precludes participation

Egyéb

• HTLV-ATLL positive patients are excluded
• Currently Pregnant or Currently lactating parent

• Patient has the ability to provide informed consent according to the applicable regulatory and local institutional requirements.
• Male or female, aged ≥12 and ≤65 years for patients receiving MAC aged ≥12 and ≤75 years for patients receiving RIC. Patients between 75 and 80 years on RIC regimen can be enrolled with prior sponsor approval
• Patient must require first allogeneic HCT per the discretion of the treating physician
• BMI <=50 (BMI of 45.1 to 50 maybe allowed after sponsor approval)
• For treatment from Ossium product only- no suitable donor available after 3 weeks of search
• 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 for experimental arm
  • HLA fully matched (8/8 allele matched at HLA-A, -B, -C, DRB1) to an unrelated available PBSC donor for observational standard of care arm
  • HLA partially matched (4-7/8 allele matched at HLA-A, -B, -C, DRB1) to an available PBSC donor for observational standard of care arm
  • HLA haploidentical matched (4/8 allele matched at HLA-A, -B, -C, DRB1) to available PBSC donor for observational standard of care arm
  • HLA partially matched (4-8/8 allele matched at HLA-A, -B, -C, DRB1) to an available living bone marrow donor for optional observational standard of care arm
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Patient with malignant hematologic disease including:
  • 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 or
  • MDS without Grade 3 fibrosis (Patients with Grade 1 and Grade 2 fibrosis can be enrolled with prior sponsor approval)
  • Chronic Lymphocytic Leukemia (CLL) eligible for allogeneic transplant or
  • Chronic Myeloid leukemia (CML) eligible for allogeneic transplant
  • Chemosensitive 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
  • Other rare hematological malignancy indications eligible for allogenic transplant will require prior sponsor review and approval
  • Absence of active CNS disease due to underlying hematological disease
• Karnofsky performance status score ≥70% (MAC) or ≥60% (RIC)
• HCT comorbidity index (HCT-CI) ≤5
• Adequate organ function defined as:
  • Cardiac: LVEF at rest ≥40% (RIC) or LVEF at rest ≥45% (MAC)
  • Pulmonary: DLCO, FEV1, FVC ≥50% predicted by pulmonary function tests (PFTs). DLCO value may be corrected (dinakara correction) for hemoglobin.
  • Hepatic: total bilirubin ≤2.0 mg/dL (except Gilbert syndrome ), and ALT, AST, and ALP <3 x upper limit normal (ULN), unless ALT, AST, and/or ALP are disease related
  • Renal: CrCl> 45 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)) or Cystatin-C test.