Evaluating Orca-Q in patients receiving stem cell transplants for blood cancers

A Phase 1 Dose Escalation and Expansion Study of Orca-Q, an Engineered Donor Graft Derived From Mobilized Peripheral Blood, in Recipients Undergoing Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancies

This study is testing a new type of donor graft called OrcaGraft to see if it can make stem cell transplants safer and more effective for people with blood cancers like leukemia.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 300 (estimated)
• Ages: 12 Years to 78 Years
• Sex: All
• Sponsor: Orca Biosystems, Inc. (Industry-sponsored)
• Drugs / interventions: alemtuzumab, cyclophosphamide
• Locations: 9 sites (Duarte, California and 8 other locations)
• Trial ID: NCT03802695 on ClinicalTrials.gov

What this trial studies

This phase 1 study aims to assess the safety, tolerability, and efficacy of engineered donor grafts known as OrcaGraft (Orca-Q) in patients undergoing myeloablative allogeneic hematopoietic cell transplantation for various hematologic malignancies. Participants will be closely monitored for any adverse effects and the overall effectiveness of the treatment. The study focuses on individuals diagnosed with acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndromes, and other related conditions. The goal is to improve transplant outcomes and patient survival rates.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 65 with specific types of blood cancers who are scheduled for a stem cell transplant.

Not a fit: Patients who have previously undergone allogeneic stem cell transplants or are currently on immunosuppressive therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could enhance the effectiveness of stem cell transplants and improve survival rates for patients with blood cancers.

How similar studies have performed: While this approach is innovative, similar studies have shown promise in improving transplant outcomes, indicating potential for success.

Eligibility 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

Where this trial is running

Duarte, California and 8 other locations

• City of Hope — Duarte, California, United States (Recruiting)
• UC Davis — Sacramento, California, United States (Recruiting)
• Stanford Health Care — Stanford, California, United States (Recruiting)
• Moffitt Cancer Center — Tampa, Florida, United States (Recruiting)
• Emory University — Atlanta, Georgia, United States (Active_not_recruiting)
• The University of Kansas Hospital — Kansas City, Kansas, United States (Withdrawn)
• Ohio State University — Columbus, Ohio, United States (Active_not_recruiting)
• University of Texas MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)
• Froedtert Memorial Lutheran Hospital — Milwaukee, Wisconsin, United States (Withdrawn)

Study contacts

• Study coordinator: Tamara Zharkevich, MD, PhD

Conditions Acute Myeloid Leukemia; Myelodysplastic Syndromes; Mixed Phenotype Acute Leukemia; Acute Lymphoblastic Leukemia