Clinical trial NCT05316701: Precision-T: A Randomized Study of Orca-T in Recipients Undergoing Allogeneic Transplantation for Hematologic Malignancies
Official title: A Randomized Phase III Trial of Patients With Advanced Hematologic Malignancies Undergoing Allogeneic Hematopoietic Cell Transplantation With Either Orca-T, a T-cell-Depleted Graft With Additional Infusion of Conventional T Cells and Regulatory T Cells, or Standard-of-Care Allogeneic Graft
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Acute Myeloid Leukemia
Acute Lymphoid Leukemia
Mixed Phenotype Acute Leukemia
Undifferentiated Leukemia
Myelodysplastic Syndrome
Acute Leukemia
Therapy-Related Myelodysplastic Syndrome
Keywords: hematopoietic stem cell transplantation
acute leukemia
Myelodysplastic syndromes
matched related donor
matched unrelated donor
myelodysplastic syndrome
Lead sponsor: Orca Biosystems, Inc.
Sponsor class: INDUSTRY
First posted: 2022-04-07
Enrollment: 174
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The Phase III is a randomized, open-label, multicenter study comparing outcomes between patients receiving Orca-T followed by single-agent tacrolimus or standard-of-care (SOC) control followed by dual agent, tacrolimus-based Graft-versus-Host-Disease (GVHD) prophylaxis regimen
Primary purpose: TREATMENT

Brief summary: This study will evaluate the safety, tolerability, and efficacy of Orca-T, an allogeneic stem cell and T-cell immunotherapy biologic manufactured for each patient (transplant recipient) from the mobilized peripheral blood of a specific, unique donor. It is composed of purified hematopoietic stem and progenitor cells (HSPCs), purified regulatory T cells (Tregs), and conventional T cells (Tcons) in participants undergoing myeloablative allogeneic hematopoietic cell transplant transplantation for hematologic malignancies.

This posting represents the Phase III component of Precision-T. The Precision-T Ph1b component is described under NCT04013685.

Detailed description: Cross reference NCT04013685

Eligibility criteria: Key Inclusion Criteria:

* Matched to a related or unrelated donor who is an 8/8 match for HLA-A, -B, -C, and DRB1
* Diagnosed with one of the following diseases:

  * Acute myeloid, lymphoid or mixed phenotype leukemia in complete remission (CR) or CR with incomplete hematologic recovery (CRi), with or without the presence of known minimal residual disease
  * Myelodysplastic syndromes (MDS) that are indicated for alloHSCT per 2017 International Expert Panel recommendations and/or have therapy-related/secondary MDS, with ≤ 10% blast burden in the bone marrow
* Planned to undergo MA-alloHCT including one of the following myeloablative conditioning regimens:

  * TBI/Cy
  * TBI/Etoposide
  * BFT
* 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%
* Negative serum or urine beta-HCG test in females of childbearing potential
* ALT/AST \< 3 times ULN
* Recipients in screening must screen negative for SARS-CoV-2 RNA using a PCR-based test
* Disease Risk Index (DRI) overall risk categorization of intermediate or high
* Total bilirubin ≤ upper limit of normal (ULN)
* Estimated glomerular filtration rate (eGFR) ≥ 60 mL/minute

Key Exclusion Criteria:

* 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.
* Planned donor lymphocyte infusion (DLI)
* Planned pharmaceutical in vivo or ex vivo T cell depletion
* Recipient positive anti-donor HLA antibodies against a mismatched allele in the selected donor
* Karnofsky performance score \< 70%
* Hematopoietic cell transplantation-specific Comorbidity Index (HCT-CI) \> 4
* Uncontrolled bacterial, viral or fungal infections at time of enrollment
* Seropositive for HIV-1 or -2, HTLV-1 or -2, Hepatitis B sAg, Hepatitis C antibody
* Known allergy or hypersensitivity to, or intolerance of, tacrolimus
* Documented allergy or hypersensitivity to iron dextran or bovine, murine, algal or Streptomyces avidinii proteins
* 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
* Psychosocial circumstances that preclude the patient being able to go through transplant or participate responsibly in follow up care
* Women who are pregnant or breastfeeding
* Women of childbearing potential (WOCBP) or men who have sexual contact with WOCBP unwilling to use effective forms of birth control or abstinence for one year after transplantation

Primary outcomes:
measure: Chronic Graft-versus-Host-Disease-free Survival
timeFrame: Randomization through 730 days post transplant
Secondary outcomes:
measure: Time to moderate or severe cGVHD
timeFrame: Randomization through 730 days post transplant
measure: Graft-versus-Host Disease and Relapse-free survival (GRFS) up to 1 year
timeFrame: Day 0 through 365 days post-transplant
measure: Overall Survival
timeFrame: 730 days after end of enrollment
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center
state: California
city: Sacramento
country: United States
facility: UC Davis
state: California
city: Stanford
country: United States
facility: Stanford Health Care
state: California
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Miami
country: United States
facility: University of Miami Hospital and Clinics - Sylvester Comprehensive Cancer Center
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute - Emory University
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health System - Michigan Medicine
state: Michigan
city: New York
country: United States
facility: Weill Cornell Medicine - New York-Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Oklahoma City
country: United States
facility: OU Health Stephenson Cancer Center
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health & Sciences University - Knight Cancer Institute
state: Oregon
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
References: