Abatacept for Leukemia

Overseen By Leland Metheny, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Leland Metheny

Must be taking: Tacrolimus, MMF

Disqualifiers: Inadequate organ function, uncontrolled illness, pregnancy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The goal of this clinical trial is to see if adding abatacept to tacrolimus and MMF prevents or reduces the chances of acute graft versus host disease which is a complication that can occur after transplant in participants with blood cancer. The usual therapy for graft versus host disease prevention after a cord blood transplant includes tacrolimus and MMF. The main question this clinical trial aims to answer is whether or not abatacept will be safe and effective in reducing aGVHD rates in dCBT.

Participants will:

* Partake in exams, tests, and procedures as part of usual cancer care.

* Partake in conditioning, which is the treatment that is given before a transplant.

* Have a cord blood transplant.

* Partake in radiation following the transplant.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, it mentions that concurrent therapy for certain conditions like testicular leukemia and CNS lymphoma is allowed, so you might be able to continue some treatments. It's best to discuss your specific medications with the trial team.

Is abatacept safe for humans?

Abatacept, also known as Orencia, has been studied for safety in patients with rheumatoid arthritis. In these studies, the overall safety profile was similar to placebo, with low rates of serious infections and malignancies. However, there was a case of squamous-cell carcinoma possibly linked to abatacept, indicating the need for more research on long-term risks. ^{1 2 3 4 5}

How does the drug Abatacept differ from other leukemia treatments?

Abatacept is unique because it is primarily used to treat autoimmune conditions like rheumatoid arthritis by modulating the immune system, whereas most leukemia treatments focus on directly targeting cancer cells or their growth pathways. This approach may offer a novel way to manage leukemia by potentially altering the immune environment around the cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Leland Metheny, MD

Principal Investigator

University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with certain blood cancers like leukemia, lymphoma, and myelodysplastic syndrome. It's also open to those with specific genetic conditions such as Klinefelter or Triple X Syndrome. Participants must be suitable for a cord blood transplant and able to undergo pre-transplant conditioning treatments including radiation.

Inclusion Criteria

I can carry out normal activities with minimal symptoms.

Patients with specific cord blood unit requirements

Subjects must have the ability to understand and sign a written informed consent document

Exclusion Criteria

Patients with uncontrolled inter-current illness

Any condition that would interfere with full participation in the study

Hematopoietic Cell Transplantation Comorbidity index greater than 5

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning

Participants undergo conditioning treatment before the transplant, including Cyclophosphamide, Fludarabine, Thiotepa, and Total Body Irradiation

2 weeks

Transplant

Participants receive a double umbilical cord blood transplant

1 day

Radiation

Participants undergo radiation following the transplant

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments for aGVHD and other outcomes

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Abatacept

Trial Overview The study tests if adding abatacept to the standard graft versus host disease prevention (which includes tacrolimus and MMF) can reduce complications after a double umbilical cord transplant in blood cancer patients. The safety and effectiveness of abatacept in this context are being evaluated.

How Is the Trial Designed?

Group I: Cy/Flu/Thio/TBI + dCBT + Tac/MMF + Abatacept Experimental Treatment 8 Interventions

Cyclophosphamide (Cy), fludarabine (Flu), thiotepa (Thio), and total body irradiation (TBI) is the preparative regimen for Double Umbilical Cord Transplant (dCBT). Graft-versus-host disease prophylaxis will consist of tacrolimus (Tac) and mycophenolate mofetil (MMF). Abatacept will be administered.

Who Is Running the Clinical Trial?

Leland Metheny

Lead Sponsor

Trials

6

Recruited

80+

Published Research Related to This Trial

The study found that 60% of rheumatoid arthritis patients were aware of the patient alert cards (PACs) for abatacept, and those who received the PACs had significantly better knowledge about the risk of infections compared to those who did not (64% vs 46%).

Among healthcare professionals, 90% were aware of the PACs, and those who accessed the cards had a higher understanding of infection risks (91% vs 73%), indicating that PACs effectively enhance safety knowledge for both patients and healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Linking process indicators and clinical/safety outcomes to assess the effectiveness of abatacept (ORENCIA) patient alert cards in patients with rheumatoid arthritis. Artime, E., Kahlon, R., Méndez, I., et al.[2021]

Recent advancements in leukemia treatments have led to high cure rates, such as over 90% for hairy cell leukemia with cladribine and rituximab, and 80-90% for acute promyelocytic leukemia using all-trans retinoic acid and arsenic trioxide.

Chronic lymphocytic leukemia, once considered incurable, may now be potentially curable with targeted therapies like Bruton tyrosine kinase inhibitors and venetoclax, showcasing the significant progress in leukemia treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The cure of leukemia through the optimist's prism. Kantarjian, HM., Jain, N., Garcia-Manero, G., et al.[2023]

Abatacept is effective in treating moderate-to-severe rheumatoid arthritis (RA) in patients who have not responded adequately to other treatments, showing improvements in symptoms, physical function, and quality of life across various RA populations.

The safety profile of abatacept is comparable to that of nonbiologic DMARDs, with supportive evidence from meta-analyses and real-world studies, indicating it can be a safe option for RA management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on the use of abatacept for the treatment of rheumatoid arthritis. Vicente Rabaneda, EF., Herrero-Beaumont, G., Castañeda, S.[2015]

Abatacept significantly improves health outcomes in patients with rheumatoid arthritis, showing higher likelihoods of achieving American College of Rheumatology (ACR) response rates compared to placebo and other treatments, based on a meta-analysis of 13 randomized control trials involving 5978 patients.

Patients treated with abatacept experienced fewer adverse events compared to those receiving other biologic disease-modifying anti-rheumatic drugs, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of efficacy and safety of abatacept for rheumatoid arthritis: systematic review and meta-analysis. Mohamed Ahamada, M., Wu, X.[2023]

Abatacept, used in combination with methotrexate for rheumatoid arthritis, demonstrated a safety profile similar to placebo in a study involving 2,944 patients, with comparable rates of adverse events and serious infections.

The treatment showed low levels of immunogenicity and did not increase the risk of autoimmune events or affect vaccination responses, indicating it is well-tolerated and safe for long-term use in RA patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of T-cell co-stimulation modulation with abatacept in patients with rheumatoid arthritis. Sibilia, J., Westhovens, R.[2017]

Citations

1. Italy pubmed.ncbi.nlm.nih.gov

Analysis of efficacy and safety of abatacept for rheumatoid arthritis: systematic review and meta-analysis. [2023]

2. Italy pubmed.ncbi.nlm.nih.gov

Safety of T-cell co-stimulation modulation with abatacept in patients with rheumatoid arthritis. [2017]

3. England pubmed.ncbi.nlm.nih.gov

Linking process indicators and clinical/safety outcomes to assess the effectiveness of abatacept (ORENCIA) patient alert cards in patients with rheumatoid arthritis. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Update on the use of abatacept for the treatment of rheumatoid arthritis. [2015]

5. England pubmed.ncbi.nlm.nih.gov

Squamous-cell carcinoma of the tongue following therapy of rheumatoid arthritis with abatacept. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

The cure of leukemia through the optimist's prism. [2023]

7. Austria pubmed.ncbi.nlm.nih.gov

[Therapy of acute leukemia in adults]. [2007]

8. United States pubmed.ncbi.nlm.nih.gov

Promising approaches in acute leukemia. [2019]

9. Germany pubmed.ncbi.nlm.nih.gov

All-trans retinoic acid plus low doses of cytarabine for the treatment of "poor-risk" acute myeloid leukemias. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

The Management of Relapsed and Refractory Acute Myeloid Leukaemia in Adults. [2019]