A Study of Engineered Donor Grafts (TregGraft/Orca-T) in Recipients Undergoing Allogeneic Transplantation for Hematologic Malignancies

Sponsor

Orca Biosystems, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04013685

Collaborator

(none)

Enrollment

Locations

Arm

36.3

Anticipated Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will evaluate the safety, tolerability, and efficacy of an engineered donor graft ("TregGraft"/"Orca-T", a T-cell-Depleted Graft With Additional Infusion of Conventional T Cells and Regulatory T Cells) in participants undergoing myeloablative allogeneic hematopoietic cell transplant transplantation for hematologic malignancies.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia Acute Lymphoid Leukemia Myelodysplastic Syndromes Acute Leukemia Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)	Biological: TregGraft (Orca-T)	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

84 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Multicenter Phase Ib Trial for Patients With Advanced Hematologic Malignancies Undergoing Allogeneic Hematopoietic Cell Transplantation With TregGraft (Orca-T), a T-cell-Depleted Graft With Additional Infusion of Conventional T Cells and Regulatory T Cells

Actual Study Start Date :

Nov 21, 2019

Anticipated Primary Completion Date :

Sep 30, 2022

Anticipated Study Completion Date :

Nov 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Subjects with Acute Leukemia or Myelodysplasic Syndrome, Myelofibrosis, or BPDCN This is a non-randomized, single-arm study. Patients will be grouped based on their underlying disease: Group 1 will enroll subjects planning to undergo myeloablative allogeneic hematopoietic cell transplantation (MA-alloHCT) for the treatment of either acute myeloid, lymphoid or mixed phenotype leukemia in complete remission (CR) or CR with incomplete hematologic recovery (CRi), and with no known minimal residual disease positivity. Group 2 will enroll subjects Subjects planning to undergo MA-alloHCT for acute myeloid, lymphoid or mixed phenotype leukemia that is either: not in morphologic CR with bone marrow infiltration by leukemic blasts of <= 10%, or in morphologic CR with evidence of minimal residual positivity by either multiparameter flow cytometric analysis or by a nucleic acid-based technique. Group 3 will enroll subjects planning to MA-alloHCT for high or very high risk myelodysplasic syndrome (MDS) myelodysplastic syndromes, myelofibrosis or BPDCN	Biological: TregGraft (Orca-T) engineered donor allograft

Arm

Intervention/Treatment

Experimental: Subjects with Acute Leukemia or Myelodysplasic Syndrome, Myelofibrosis, or BPDCN

This is a non-randomized, single-arm study. Patients will be grouped based on their underlying disease: Group 1 will enroll subjects planning to undergo myeloablative allogeneic hematopoietic cell transplantation (MA-alloHCT) for the treatment of either acute myeloid, lymphoid or mixed phenotype leukemia in complete remission (CR) or CR with incomplete hematologic recovery (CRi), and with no known minimal residual disease positivity. Group 2 will enroll subjects Subjects planning to undergo MA-alloHCT for acute myeloid, lymphoid or mixed phenotype leukemia that is either: not in morphologic CR with bone marrow infiltration by leukemic blasts of <= 10%, or in morphologic CR with evidence of minimal residual positivity by either multiparameter flow cytometric analysis or by a nucleic acid-based technique. Group 3 will enroll subjects planning to MA-alloHCT for high or very high risk myelodysplasic syndrome (MDS) myelodysplastic syndromes, myelofibrosis or BPDCN

Biological: TregGraft (Orca-T)

engineered donor allograft

Outcome Measures

Primary Outcome Measures

TregGraft (Orca-T), with single agent GVHD prophylaxis [365 days]

Secondary Outcome Measures

1-year overall survival (OS) [365 days]
1-year overall survival (OS)
1 year graft-versus-host-disease-free and relapse-free survival (GRFS) [365 days]
1 year graft-versus-host-disease-free and relapse-free survival (GRFS)
incidence and severity of acute and chronic graft vs host disease (GvHD) [365 days]
incidence and severity of acute and chronic graft vs host disease (GvHD)
incidence of serious infections [365 days]
incidence of serious infections
incidence and timing of engraftment [28 days]
incidence and timing of engraftment of platelets and neutrophils

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Recipients must meet all of the following criteria:

Patients must diagnosed with one of the following histopathologically confirmed diseases, for which a myeloablative hematopoietic stem cell transplant (HCT) is planned:

acute myeloid, lymphoid or mixed phenotype leukemia
high or very high risk myelodysplastic syndromes
Myelofibrosis
Blastic Plasmacytoid Dendritic Cell Neoplasm

Patients with active acute leukemia (i.e. not in morphologic complete response) must have bone marrow infiltration by leukemic blasts of <= 10%,
Patients must be matched to a related or unrelated donor
Estimated glomerular filtration rate (eGFR) > 50 mL/minute
Cardiac ejection fraction at rest ≥ 45% or shortening fraction of ≥ 27% by echocardiogram or radionuclide scan (MUGA)
Diffusing capacity of the lung for carbon monoxide (DLCO) (adjusted for hemoglobin) ≥ 50%
Total bilirubin < 2 times upper limit of normal (ULN) (patients with Gilbert's syndrome may be included where hemolysis has been excluded) and ALT/AST < 3 times ULN

Key Exclusion Criteria:

Recipients meeting any of the following exclusion criteria will not be eligible:

History of prior allogeneic HCT
Currently receiving corticosteroids or other immunosuppressive therapy. Topical corticosteroids or oral systemic corticosteroid doses less than or equal to 10 mg/day are allowed.
Pre-planned donor lymphocyte infusion (DLI)
Planned pharmaceutical in vivo or ex vivo T cell depletion
Positive for anti-donor HLA antibodies against an allele in the selected donor
Karnofsky performance score < 70%
Hematopoietic cell transplantation-specific Comorbidity Index (HCT-CI) > 4
Uncontrolled bacterial, viral or fungal infections (currently taking antimicrobial therapy and with progression or no clinical improvement) at time of enrollment
Seropositive for HIV-1 or -2 antibody, HTLV-1 or -2 antibody, Hepatitis B sAg, or Hepatitis C antibody
Any uncontrolled autoimmune disease requiring active immunosuppressive treatment
Concurrent malignancies or active disease within 1 year, except non-melanoma skin cancers that have been curatively resected
Women who are pregnant or breastfeeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope	Duarte	California	United States	91010
2	Ronald Reagan UCLA Medical Center	Los Angeles	California	United States	90095
3	UC Davis	Sacramento	California	United States	95817
4	Stanford Health Care	Stanford	California	United States	94305
5	Winship Cancer Institute - Emory University	Atlanta	Georgia	United States	30322
6	University of Chicago	Chicago	Illinois	United States	60637
7	The University of Kansas Hospital	Kansas City	Kansas	United States	66160
8	Weill Cornell	New York	New York	United States	10065
9	Oregon Health & Sciences University - Knight Cancer Institute	Portland	Oregon	United States	97239
10	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
11	Vanderbilt University	Nashville	Tennessee	United States	37232
12	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77054
13	Texas Transplant Institute	San Antonio	Texas	United States	78229
14	University of Utah - Huntsman Cancer Institute	Salt Lake City	Utah	United States	84112