Engineered Donor Grafts (Orca-T) for Blood Cancers

Not currently recruiting at 21 trial locations

Overseen By James S McClellan, MD PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Orca Biosystems, Inc.

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Prior allogeneic HCT, HIV, 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: Unknown

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new treatment called Orca-T for individuals with certain blood cancers. Orca-T is a specialized stem cell and immune cell therapy derived from a donor's blood, designed to assist patients undergoing a stem cell transplant. It targets individuals with specific types of leukemia or myelodysplastic syndromes (a group of blood disorders) who require a transplant and have a matching donor. Suitable candidates have active blood cancer or are in remission but need intensive treatment. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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

The trial requires that you are not currently receiving corticosteroids or other immunosuppressive therapy, except for topical corticosteroids or oral systemic corticosteroid doses less than or equal to 10 mg/day. Other medications are not specifically mentioned, so it's best to discuss your current medications with the trial team.

Is there any evidence suggesting that Orca-T is likely to be safe for humans?

Research has shown that Orca-T, a new treatment for blood cancers, holds promise for safety and effectiveness. One study showed that Orca-T achieved a 94% survival rate after one year, surpassing the usual stem cell transplant. This suggests that patients might experience better outcomes.

Although researchers are still studying the treatment, these results are encouraging. Orca-T uses special donor cells to combat cancer and aims to reduce common side effects. It is designed to be gentle on the body, and many patients have experienced positive results with fewer severe reactions.

Orca-T remains in early testing, so researchers continue to gather safety information. However, these findings suggest it could be a safer, more effective option for people with blood cancers. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Orca-T is unique because it uses engineered donor grafts in an allogeneic hematopoietic cell transplant (HCT) to treat blood cancers like acute leukemia, myelodysplastic syndrome, and BPDCN. Unlike traditional treatments that rely on standard donor cells, Orca-T involves a specially engineered graft designed to enhance the effectiveness and safety of the transplant process. Researchers are excited about Orca-T because it has the potential to reduce the risk of complications like graft-versus-host disease, which is a significant concern with conventional HCT. This innovative approach aims to improve patient outcomes and offer new hope for those with these challenging conditions.

What evidence suggests that Orca-T might be an effective treatment for blood cancers?

Research has shown that Orca-T might be a promising treatment for blood cancers like acute leukemia and myelodysplastic syndrome (MDS). In earlier studies, the survival rate for patients using Orca-T was 94% after one year, surpassing the 83% survival rate with standard stem cell transplants. Additionally, after three years, 86% of patients with conditions like AML, ALL, and MDS remained alive. Orca-T also appears to lower the risk of chronic graft-versus-host disease (cGVHD), a common issue after transplants. These findings suggest that Orca-T could improve survival and reduce complications for patients with certain blood cancers.

In this trial, all enrolled subjects will receive an allogeneic HCT with the Orca-T product, as it is a non-randomized, single-arm study. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with certain blood cancers like acute leukemia or myelodysplastic syndrome who need a stem cell transplant. They must be relatively healthy, with good liver, kidney, heart and lung function, not have other active cancers or serious infections, and can't be pregnant or breastfeeding. Participants should match an 8/8 HLA donor and cannot have had a previous transplant.

Inclusion Criteria

I am 18-65 with a certain type of leukemia and plan to have a stem cell transplant.

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)

Exclusion Criteria

Seropositive for HIV-1 or -2 antibody, HTLV-1 or -2 antibody, Hepatitis B sAg, or Hepatitis C antibody

I have had a stem cell transplant from a donor.

I currently have an infection that isn't getting better with treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an allogeneic hematopoietic cell transplant with the Orca-T product

4 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including incidence of aGVHD and graft failure

52 weeks

Monthly visits (in-person)

Long-term follow-up

Participants are monitored for long-term outcomes such as overall survival and chronic GvHD

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Orca-T

Trial Overview The study tests 'Orca-T', an engineered donor graft designed to improve outcomes in patients receiving bone marrow transplants for various hematologic malignancies. It aims to see if this new method is safe and works well compared to traditional approaches.

How Is the Trial Designed?

Group I: Subjects with Acute Leukemia or Myelodysplastic Syndrome, or BPDCN Experimental Treatment 1 Intervention

This is a non-randomized, single-arm study. All enrolled subjects will receive an allogeneic HCT with the Orca-T product.

Orca-T is already approved in United States for the following indications:

Approved in United States as Orca-T for:

• Acute Lymphoblastic Leukemia (ALL)
• Acute Myeloid Leukemia (AML)
• Myelodysplastic Syndrome (MDS)
• Myelofibrosis

Who Is Running the Clinical Trial?

Orca Biosystems, Inc.

Lead Sponsor

Trials

8

Recruited

750+

Citations

1. 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 Overall survival with Orca-T was 94% compared to 83% with alloHSCT at one year, and the cumulative incidence of moderate-to-severe cGvHD was ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06195891

NCT06195891 | Orca-T Following Chemotherapy and Total ... Giving total marrow and lymphoid irradiation and chemotherapy followed by Orca -T cells may be an effective treatment for patients with AML, ALL or MDS.

3. ajmc.com ajmc.com/view/orca-t-shows-efficacy-reduced-gvhd-risk-in-acute-leukemia-mds

Orca-T Shows Efficacy, Reduced GVHD Risk in Acute ... Orca-T, an investigational allogeneic T-cell immunotherapy, improved cGVHD-free survival compared with allo-HSCT in patients with acute leukemia ...

4. orcabio.com orcabio.com/orca-bio-presents-three-year-survival-data-with-orca-t-in-patients-with-hematological-malignancies-at-the-66th-ash-annual-meeting/

Orca Bio Presents Three-Year Survival Data with Orca-T® ... Three-year overall survival with Orca-T allogeneic T-cell immunotherapy was 86% for patients with AML, ALL and MDS compared to 67% in a non-randomized ...

5. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/3560/502299/Phase-1-Trial-Results-for-Patients-with-Advanced

Phase 1 Trial Results for Patients with Advanced Hematologic ... Conclusions: These early results demonstrate that Orca-T is a safe and feasible transplant strategy in the RIC setting for patients with ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT07216443

Study Details | NCT07216443 | Reduced Intensity or ... This study will evaluate the safety, tolerability, and efficacy of Orca-T in participants undergoing reduced intensity or non-myeloablative ...

7. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/230/503053/Optimizing-Outcomes-with-Myeloablative

Efficacy and Safety of Precision Engineered Orca-T in Patients ... Optimizing outcomes with myeloablative conditioning in older patients: efficacy and safety of precision engineered orca-t in patients > 55 years old with ...