Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Mixed Phenotype Acute Leukemia, Myelodysplastic Syndromes
Conditions
Brief summary
This study will evaluate the safety, tolerability, and efficacy of engineered donor grafts ("OrcaGraft"/"Orca-Q") in participants undergoing allogeneic hematopoietic cell transplant (alloHCT) transplantation for hematologic malignancies.
Interventions
BIOLOGICALOrcaGraft (Orca-Q)
engineered donor allograft
Sponsors
Orca Biosystems, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 78 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Age at the time of enrollment: 1. For MAC with fully matched donor (Arm A with 8/8 donor and Arm C) and NMA/RIC: Age ≥ 12 and ≤ 78 years 2. For MAC with mismatched donors (Arm A with 7/8 donor and Arm B): Age ≥ 12 and ≤ 65 years 2. Diagnosed acute myeloid, lymphoblastic or mixed phenotype leukemia, or high or very high risk myelodysplastic syndrome (MDS) either in complete remission (CR) or with ≤ 10 percent of blast cells in bone marrow (BM) 3. Indicated for allogeneic hematopoietic stem cell transplant (alloHCT) 4. Matched to a 8/8 or 7/8 related or unrelated donor, or to a related haploidentical donor 5. Estimated glomerular filtration rate (eGFR) \> 50 mL/minute (MAC with tacrolimus) or \> 30 mL/minute (NMA/RIC or MAC without tacrolimus) 6. Cardiac parameters: Cardiac ejection fraction ≥ 45 percent (MAC) or ≥ 40 percent (NMA/RIC) 7. Diffusing capacity of the lung for carbon monoxide (DLCO) (adjusted for hemoglobin) ≥ 50 percent for MAC or ≥ 40 percent for NMA/RIC 8. Liver function: Total bilirubin \< 1.5 times upper limit of normal (ULN) (MAC) or \< 3 times ULN (NMA/RIC); alanine transaminase (ALT)/aspartate transaminase (AST) \< 3 times ULN (MAC) or \< 5 times ULN (NMA/RIC) 9. Participants enrolling on NMA/RIC-alloHCT arms must be deemed unfit for a myeloablative alloHCT per assessment of the principal investigator (PI) Key
Exclusion criteria
1. Prior alloHCT 2. Currently receiving corticosteroids or other immunosuppressive therapy except for approved disease-specific therapy for the patient's underlying hematologic malignancy. Topical corticosteroids or oral systemic corticosteroid doses less than or equal to 10 mg/day are allowed 3. Planned donor lymphocyte infusion (DLI) 4. Planned pharmaceutical in vivo or ex vivo T cell depletion, e.g., post-transplant cyclophosphamide (Cy) or alemtuzumab 5. Positive anti-donor HLA antibodies against a mismatched allele in the selected donor 6. Low performance score: For MAC: Karnofsky Performance Score (KPS) \< 70 percent, For NMA/RIC: \<60 percent 7. High HCT-specific Comorbidity Index (HCT-CI): For MAC \> 4, For NMA/RIC \>6 8. Uncontrolled bacterial, viral or fungal infections (currently taking antimicrobial therapy and with progression or no clinical improvement) at time of enrollment 9. Seropositive for human immunodeficiency virus (HIV)-1 or -2, human T-lymphotropic virus (HTLV)-1 or -2 or Hepatitis B surface antigen (HbsAg) or anti-Hepatitis C virus (HCV) antibody (Ab) 10. Any uncontrolled autoimmune disease requiring active immunosuppressive treatment 11. Concurrent malignancies or active disease within 1 year, except non-melanoma skin cancers that have been curatively resected. Patients with concurrent indolent hematologic malignancies that do not require active treatment and are under active surveillance only (such as CLL, low-grade lymphomas, smoldering MM, MZL) may be included with the approval of Medical Monitor 12. History of idiopathic or secondary myelofibrosis 13. Women who are pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Limiting Toxicities through Day +28 (dose escalation) | 28 Days after administration of Orca-Q/OrcaGraft | Safety and tolerability of Orca-Q (formerly OrcaGraft) in adults undergoing myeloablative allogeneic hematopoietic cell transplantation (MA-alloHCT) will be evaluated by identification of the following dose limiting toxicities: Grade ≥ 3 infusion-related reaction or cytokine release syndrome, Grade ≥ 3 acute GVHD, Any Grade ≥ 3 treatment-related non-hematologic event not clearly related to the underlying malignancy, intercurrent infection, the HCT conditioning regimen, or other pre-existing medical condition |
| Primary Graft failure through Day +28 (dose expansion) | 28 Days after administration of Orca-Q/OrcaGraft | Primary graft failure in the dose expansion phase, defined as being alive without recovery of neutrophils during the evaluation period |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Neutrophil Engraftment through Day +28 | 28 days after administration of Orca-Q/OrcaGraft | Neutrophil engraftment defined as an absolute neutrophil count of \>/=500/mm3 for 3 consecutive days |
| Platelet Engraftment through Day +50 | 50 days after administration of Orca-Q/OrcaGraft | Platelet engraftment is defined as achieving a platelet count \> 20,000/mm3 for 3 consecutive days without platelet transfusion in the preceding 7 days, by Day +50 |
| Secondary Graft Failure through Day +100 | 100 days after administration of Orca-Q/OrcaGraft | Secondary graft failure is defined as neutrophil engraftment followed by subsequent decline in absolute neutrophil counts \< 500 cells/μL, unresponsive to growth factor therapy, by Day +100 |
| Acute GVHD through Day +100 | 100 days after administration of Orca-Q/OrcaGraft | Acute GVHD will be staged and graded per Mount Sinai Acute GvHD International Consortium (MAGIC) Standardization criteria |
| Chronic GVHD through Day +365 | 365 days after administration of Orca-Q/OrcaGraft | Chronic GVHD will be diagnosed per 2014 International NIH Chronic GVHD Diagnosis and Staging Consensus Working Group criteria |
| Incidence of Non-relapse Mortality (NRM) through Day +365 | 365 days after administration of Orca-Q/OrcaGraft | NRM is defined as death without evidence of disease recurrence |
| Incidence of Disease Relapse through Day +365 | 365 days after administration of Orca-Q/OrcaGraft | Recurrence of primary disease for transplant |
| GVHD-free and Relapse-free Survival (GRFS) through Day +365 | 365 days after administration of Orca-Q/OrcaGraft | Survival free from GVHD and relapse |
| Disease-free Survival (DFS) through Day +365 | 365 days after administration of Orca-Q/OrcaGraft | DFS is the time from date of transplant to death or relapse, whichever comes first. |
| Overall Survival through Day +365 | 365 days after administration of Orca-Q/OrcaGraft | OS is defined as the time from the date of transplant to the date of death from any cause or, for surviving patients, to the date of last follow-up. |
Countries
United States
Contacts
CONTACTTamara Zharkevich, MD, PhD
CONTACTJames S McClellan, MD PhD
STUDY_DIRECTORJames S McClellan, MD, PhD
Orca Biosystems, Inc.
Outcome results
None listed