A Phase 1 Study of Orca-Q in Recipients Undergoing Allogeneic Transplantation for Hematologic Malignancies

Phase 1

Recruiting

• Conditions: Mixed Phenotype Acute Leukemia; Myelofibrosis; Chronic Myeloid Leukemia; Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Myelodysplastic Syndromes
• Interventions: Biological: OrcaGraft (Orca-Q)

• Registration Number: NCT03802695
• Lead Sponsor: Orca Biosystems, Inc.

Brief Summary

This study will evaluate the safety, tolerability, and efficacy of engineered donor grafts ("OrcaGraft"/"Orca-Q") in participants undergoing myeloablative allogeneic hematopoietic cell transplant transplantation for hematologic malignancies.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-01-10
• Study First Submitted QC: 2019-01-10
• Study First Posted: 2019-01-14
• Study Start: 2019-04-08
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-01
• Last Update Posted: 2024-04-03
• Primary Completion: 2026-04
• Study Completion: 2028-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 186

Inclusion Criteria

1. Age ≥ 18 and ≤ 65 years at the time of enrollment
2. Diagnosed acute myeloid, lymphoid or mixed phenotype leukemia, or high or very high risk myelodysplasic syndrome (MDS), myelofibrosis, or chronic myeloid leukemia
3. Planned to undergo myeloablative allogeneic hematopoietic stem cell transplant (HCT)
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
6. Cardiac ejection fraction at rest ≥ 45% or shortening fraction of ≥ 27% by echocardiogram or radionuclide scan (MUGA)
7. Diffusing capacity of the lung for carbon monoxide (DLCO) (adjusted for hemoglobin) ≥ 50%
8. Total bilirubin < 1.5 times upper limit of normal (ULN) (< 3 times if attributed to Gilbert's syndrome) and ALT/AST < 3 times ULN

Key

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Exclusion Criteria

1. Prior allogeneic HCT
2. Currently receiving corticosteroids or other immunosuppressive therapy. Topical corticosteroids or oral systemic corticosteroid doses less than or equal to 10 mg/day are allowed.
3. Planned donor lymphocyte infusion (DLI)
4. Positive anti-donor HLA antibodies against a mismatched allele in the selected donor
5. Karnofsky performance score < 70% (Appendix 12.7)
6. Hematopoietic cell transplantation-specific Comorbidity Index (HCT-CI) > 4 (Appendix 12.8)
7. Uncontrolled bacterial, viral or fungal infections (currently taking antimicrobial therapy and with progression or no clinical improvement) at time of enrollment
8. Seropositive for HIV-1 or -2, HTLV-1 or -2
9. Any uncontrolled autoimmune disease requiring active immunosuppressive treatment
10. Concurrent malignancies or active disease within 1 year, except non-melanoma skin cancers that have been curatively resected
11. History of idiopathic or secondary myelofibrosis
12. Women who are pregnant or breastfeeding

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm C	OrcaGraft (Orca-Q)	Recipients with an HLA-identical related or unrelated donor; no GVHD prophylaxis given
Arm B	OrcaGraft (Orca-Q)	Recipients with haploidentical-related donors; with single-agent GVHD prophylaxis given
Arm A	OrcaGraft (Orca-Q)	Recipients with HLA-identical or 1-allele mismatched (7/8 alleles) related or unrelated donor; with single-agent GVHD prophylaxis given

Primary Outcome Measures

Name	Time	Method
Number of Dose Limiting Toxicities	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, and by instance of primary graft failure, defined as being alive without recovery of neutrophils during the evaluation period
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 Outcome Measures

Name	Time	Method
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
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
Post-Transplant Lymphoproliferative Disorder (PTLD) through Day +365	365 days after administration of Orca-Q/OrcaGraft	PTLD is defined as a biopsy consistent with the 2017 World Health Organization (WHO) classification of PTLD
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
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
Steroid-refractory acute GVHD through Day +100	100 days after administration of Orca-Q/OrcaGraft	Steroid-refractory acute GVHD will be defined as per the EBMT-NIH-CIBMTR Task Force position statement
Disease-free survival (DFS) through Day +365	365 days after administration of Orca-Q/OrcaGraft	Disease-free survival is the time from date of transplant to death or relapse, whichever comes first.
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
Treatment-emergent adverse events (TEAEs) through the safety reporting period	100 days after administration of Orca-Q/OrcaGraft	TEAEs categorized by System Organ Lass and graded according to the CTCAE v5.0
GVHD-free and relapse-free survival (GRFS) through Day +365	365 days after administration of Orca-Q/OrcaGraft	Survival free from GVHD and relapse
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.

Trial Locations

Locations (8)

The University of Kansas Hospital; 🇺🇸 Kansas City, Kansas, United States

Ohio State University; 🇺🇸 Columbus, Ohio, United States

Emory University; 🇺🇸 Atlanta, Georgia, United States

City of Hope; 🇺🇸 Duarte, California, United States

UC Davis; 🇺🇸 Sacramento, California, United States

Stanford Health Care; 🇺🇸 Stanford, California, United States

Froedtert Memorial Lutheran Hospital; 🇺🇸 Milwaukee, Wisconsin, United States

University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States