OrcaGraft for Blood Cancer

Recruiting at 6 trial locations

Overseen By Tamara Zharkevich, MD PhD

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Orca Biosystems, Inc.

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Prior HCT, HIV, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 365

Duration: 4 weeks

300 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests OrcaGraft, an engineered donor graft, to evaluate its safety and effectiveness for individuals undergoing stem cell transplants for blood cancers such as leukemia or high-risk myelodysplastic syndrome. The trial examines various methods of using OrcaGraft, based on the donor-recipient match and the type of pre-treatment administered. It suits those with leukemia or a similar condition in remission, who are planning a stem cell transplant and have a matched donor. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this innovative therapy.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop all current medications, but you cannot be on corticosteroids or other immunosuppressive therapy, except for low-dose topical or oral corticosteroids (10 mg/day or less).

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that OrcaGraft (Orca-Q) appears safe for people with blood cancers. Studies found that patients who received Orca-Q experienced low rates of graft-versus-host disease (GvHD), a condition where donor cells attack the patient's body. In these studies, patients did not require additional medication to prevent GvHD, suggesting Orca-Q is well-tolerated.

Additionally, one year after treatment, 85% of patients remained alive, demonstrating positive results without serious side effects. While these findings are encouraging, it is important to remember that this treatment is still under investigation. Further research will help confirm its safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about OrcaGraft (Orca-Q) because it offers a potentially groundbreaking approach to treating blood cancer. Unlike traditional treatments that often involve broad immunosuppressive regimens to prevent graft-versus-host disease (GVHD), OrcaGraft uses a more targeted strategy. It explores various combinations of conditioning intensity and GVHD prophylaxis to tailor the treatment to different donor types. This personalized approach aims to optimize patient outcomes and minimize side effects, offering hope for better survival rates and quality of life for blood cancer patients.

What evidence suggests that OrcaGraft might be an effective treatment for blood cancer?

Research has shown that OrcaGraft, also known as Orca-Q, shows promising results for treating blood cancers. In this trial, participants will be assigned to different treatment arms based on donor compatibility and conditioning regimen. Some arms will receive Orca-Q with single-agent GvHD prophylaxis, while others will receive dual-agent prophylaxis or no prophylaxis. Specifically, studies found that patients who received Orca-Q without additional medication to prevent graft-versus-host disease (GvHD) experienced low rates of GvHD and deaths unrelated to cancer recurrence. After one year, 85% of these patients were alive without cancer returning, and 77% were free from GvHD. These results suggest Orca-Q could be effective for individuals undergoing bone marrow transplants for blood cancers. ^{1 2 4 5 6}

Who Is on the Research Team?

James S McClellan, MD, PhD

Principal Investigator

Orca Biosystems, Inc.

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with certain blood cancers like acute leukemia or high-risk myelodysplastic syndrome. Participants must match with a donor, have good kidney and heart function, and not be pregnant or on strong immunosuppressants. Those with uncontrolled infections, other active cancers, prior transplants, or severe comorbidities cannot join.

Inclusion Criteria

Estimated glomerular filtration rate (eGFR) > 50 mL/minute

I am scheduled for a stem cell transplant from a donor.

Cardiac ejection fraction at rest ≥ 45% or shortening fraction of ≥ 27% by echocardiogram or radionuclide scan (MUGA)

Exclusion Criteria

I need assistance with my daily activities.

Seropositive for HIV-1 or -2, HTLV-1 or -2

I am not pregnant or breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Orca-Q engineered donor grafts as part of myeloablative allogeneic hematopoietic cell transplantation

4 weeks

Multiple visits for transplantation and monitoring

Follow-up

Participants are monitored for safety, efficacy, and engraftment outcomes, including neutrophil and platelet engraftment

52 weeks

Regular visits for monitoring up to 365 days post-transplant

What Are the Treatments Tested in This Trial?

Interventions

• OrcaGraft (Orca-Q)

Trial Overview The study tests 'OrcaGraft' (Orca-Q), an engineered donor graft in patients receiving bone marrow transplants for blood cancers. It aims to assess the safety and effectiveness of this new treatment approach during the transplant process.

How Is the Trial Designed?

Group I: Arm F Experimental Treatment 1 Intervention

Recipients with haploidentical-related donors undergoing NMA/RIC; with dual-agent GVHD prophylaxis given

Group II: Arm E Experimental Treatment 1 Intervention

Recipients with 1-allele mismatched (7/8 alleles) unrelated donor undergoing NMA/RIC; with dual-agent GVHD prophylaxis given

Group III: Arm D Experimental Treatment 1 Intervention

Recipients with an HLA-identical related or unrelated donor undergoing non-myeloablative (NMA)/reduced intensity conditioning (RIC); with dual agent GVHD prophylaxis

Group IV: Arm C Experimental Treatment 1 Intervention

Recipients with an HLA-identical related or unrelated donor undergoing MAC; no GVHD prophylaxis given

Group V: Arm B Experimental Treatment 1 Intervention

Recipients with haploidentical-related donors undergoing MAC; with single-agent GVHD prophylaxis given

Group VI: Arm A Experimental Treatment 1 Intervention

Recipients with human leukocyte antigen (HLA)-identical or 1-allele mismatched (7/8 alleles) related or unrelated donor undergoing myeloablative conditioning (MAC); with single-agent graft-versus-host disease (GVHD) prophylaxis given

OrcaGraft (Orca-Q) is already approved in United States for the following indications:

Approved in United States as Orca-Q for:

• Acute Myeloid Leukemia
• Acute Lymphoblastic Leukemia
• Myelodysplastic Syndromes
• Chronic Myeloid Leukemia
• Primary Myelofibrosis

Who Is Running the Clinical Trial?

Orca Biosystems, Inc.

Lead Sponsor

Trials

8

Recruited

750+

Citations

1. orcabio.com orcabio.com/orca-bio-presents-clinical-results-on-use-of-orca-q-without-gvhd-prophylaxis-in-patients-with-hematological-malignancies-at-the-66th-ash-annual-meeting/

Orca Bio Presents Clinical Results on Use of Orca-Q ... Orca-Q allogeneic T-cell immunotherapy with no GvHD prophylaxis in patients with matched donors demonstrated low rates of GvHD and non-relapse mortality.

2. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/382/530323/Preliminary-Safety-and-Efficacy-of-Myeloablative

Preliminary Safety and Efficacy of Myeloablative Orca-Q with ... The administration of Orca-Q without post-transplant pharmacological GvHD prophylaxis has shown promising clinical outcomes at the 1-year follow ...

3. onclive.com onclive.com/view/orca-q-shows-promise-in-high-risk-hematologic-cancers-and-bft-conditioning-may-synergize-with-the-agent

Orca-Q Shows Promise in High-Risk Hematologic Cancers ... Additionally, patients experienced a 1-year relapse-free survival (RFS) rate of 85% and GVHD-free RFS (GRFS) rate of 77%. The neutrophil and ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S000649712403129X

Preliminary Safety and Efficacy of Myeloablative Orca-Q ... The administration of Orca-Q without post-transplant pharmacological GvHD prophylaxis has shown promising clinical outcomes at the 1-year follow-up.

5. orcabio.com orcabio.com/orca-bio-announces-positive-results-from-the-pivotal-phase-3-study-of-investigational-orca-t-compared-to-allogeneic-stem-cell-transplant-for-the-treatment-of-hematologic-malignancies/

Press release Patients in the Orca-T group achieved an estimated overall survival (OS) of 94% compared to 83% in the alloHSCT arm at one year. "Today, ...

6. astctjournal.org astctjournal.org/article/S2666-6367(25)00197-6/fulltext

Preliminary Safety and Efficacy of Myeloablative Orca-Q ... Administration of Orca-Q without post-transplant pharmacological GvHD prophylaxis showed promising clinical outcomes at 1-year follow-up. Orca-Q offers similar ...