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

Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03802695
• Other study ID #: OGFT001-001
• Status: Recruiting
• Phase: Phase 1
• Start date: April 8, 2019
• Est. completion date: April 2028

Study information

• Verified date: April 2024
• Source: Orca Biosystems, Inc.
• Contact: James S McClellan, MD, PhD
• Phone: 1-530-414-9743
• Email: info[@]orcabiosystems.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 186
• Est. completion date: April 2028
• Est. primary completion date: April 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Key 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 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

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Acute Myeloid Leukemia
• Chronic Myeloid Leukemia
• Hematologic Neoplasms
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Mixed Phenotype Acute Leukemia
• Myelodysplastic Syndromes
• Myelofibrosis
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Biological:
• OrcaGraft (Orca-Q)
engineered donor allograft

Locations

Country	Name	City	State
United States	Emory University	Atlanta	Georgia
United States	Ohio State University	Columbus	Ohio
United States	City of Hope	Duarte	California
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	The University of Kansas Hospital	Kansas City	Kansas
United States	Froedtert Memorial Lutheran Hospital	Milwaukee	Wisconsin
United States	UC Davis	Sacramento	California
United States	Stanford Health Care	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Orca Biosystems, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Dose Limiting Toxicities	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	28 Days after administration of Orca-Q/OrcaGraft
Primary	Primary Graft failure through Day +28 (dose expansion)	Primary graft failure in the dose expansion phase, defined as being alive without recovery of neutrophils during the evaluation period	28 Days after administration of Orca-Q/OrcaGraft
Secondary	Neutrophil Engraftment through Day +28	Neutrophil engraftment defined as an absolute neutrophil count of >/=500/mm3 for 3 consecutive days	28 days after administration of Orca-Q/OrcaGraft
Secondary	Platelet engraftment through Day +50	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	50 days after administration of Orca-Q/OrcaGraft
Secondary	Secondary graft failure through Day +100	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	100 days after administration of Orca-Q/OrcaGraft
Secondary	Treatment-emergent adverse events (TEAEs) through the safety reporting period	TEAEs categorized by System Organ Lass and graded according to the CTCAE v5.0	100 days after administration of Orca-Q/OrcaGraft
Secondary	Acute GVHD through Day +100	Acute GVHD will be staged and graded per Mount Sinai Acute GvHD International Consortium (MAGIC) Standardization criteria	100 days after administration of Orca-Q/OrcaGraft
Secondary	Steroid-refractory acute GVHD through Day +100	Steroid-refractory acute GVHD will be defined as per the EBMT-NIH-CIBMTR Task Force position statement	100 days after administration of Orca-Q/OrcaGraft
Secondary	Chronic GVHD through Day +365	Chronic GVHD will be diagnosed per 2014 International NIH Chronic GVHD Diagnosis and Staging Consensus Working Group criteria	365 days after administration of Orca-Q/OrcaGraft
Secondary	Post-Transplant Lymphoproliferative Disorder (PTLD) through Day +365	PTLD is defined as a biopsy consistent with the 2017 World Health Organization (WHO) classification of PTLD	365 days after administration of Orca-Q/OrcaGraft
Secondary	Incidence of non-relapse mortality (NRM) through Day +365	NRM is defined as death without evidence of disease recurrence	365 days after administration of Orca-Q/OrcaGraft
Secondary	Incidence of disease relapse through Day +365	Recurrence of primary disease for transplant	365 days after administration of Orca-Q/OrcaGraft
Secondary	GVHD-free and relapse-free survival (GRFS) through Day +365	Survival free from GVHD and relapse	365 days after administration of Orca-Q/OrcaGraft
Secondary	Disease-free survival (DFS) through Day +365	Disease-free survival is the time from date of transplant to death or relapse, whichever comes first.	365 days after administration of Orca-Q/OrcaGraft
Secondary	Overall survival through Day +365	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.	365 days after administration of Orca-Q/OrcaGraft