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?

This trial examines whether adding abatacept (Orencia) to the usual treatment can reduce the risk of acute graft versus host disease, a serious complication after a cord blood transplant in individuals with blood cancers like leukemia. The typical treatment includes tacrolimus and MMF, and researchers aim to determine if abatacept enhances safety and effectiveness. This trial may suit those with conditions like leukemia or myelodysplastic syndromes who are preparing for a cord blood transplant. Participants will undergo standard cancer care, including exams, conditioning, and a cord blood transplant, followed by radiation. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to advancements in treatment safety and effectiveness.

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

Previous studies have shown that patients tolerate abatacept well. In trials comparing abatacept to a placebo (a harmless pill with no active medicine), side effect rates were similar. This indicates that people taking abatacept did not experience more side effects than those on the placebo. However, some evidence suggests that abatacept might slightly increase the risk of certain cancers, though researchers are still studying this.

Overall, past research indicates that abatacept is generally safe, but like any treatment, it may have risks. If there are concerns, discussing them with the trial team or a doctor is important. They can provide more detailed information and help determine if joining a trial is appropriate. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for leukemia?

Unlike the standard treatments for leukemia, which often involve chemotherapy and radiation targeting rapidly dividing cells, abatacept is unique because it works by modulating the immune system. Specifically, it targets and blocks a protein that is crucial for the activation of T-cells, which are part of the immune response. Researchers are excited about abatacept because it has the potential to reduce the risk of graft-versus-host disease, a common complication in bone marrow transplants, by preventing these immune cells from attacking the body's own tissues. This immunomodulatory approach could lead to better outcomes and fewer side effects compared to traditional therapies.

What evidence suggests that abatacept might be an effective treatment for acute graft versus host disease?

Research has shown that abatacept, included in this trial's treatment regimen, can help prevent severe graft versus host disease (GVHD) after a bone marrow transplant, with a 97.7% survival rate free of severe GVHD. This suggests it might reduce complications for blood cancer patients receiving a transplant. Previous studies have found abatacept to be safe and effective, even for those with a history of cancer. The treatment also carries a low risk of causing new cancers. These findings support its potential use in managing acute GVHD, but more research is needed to confirm these results specifically for cord blood transplants. ^{3 6 7 8 9}

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.

orenciahcp.com

orenciahcp.com/efficacy-data.html

Efficacy Data - ORENCIA® (abatacept)

However, more cases of lung cancer were observed in patients treated with ORENCIA (0.2%) than those on placebo (0%).

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10395174/

Efficacy and safety of abatacept in patients with rheumatoid ...

In our clinical practice, ABT was as effective and safe in patients with a history of malignancy as in those without.

3.

academic.oup.com

academic.oup.com/rheumatology/article/64/6/3280/8037855

Abatacept and the risk of malignancy: a meta-analysis across ...

Malignancy risk was ranked across all treatments using SUCRA: abatacept was associated with the lowest risk of malignancy, followed by TNFi and placebo in the ...

4.

answers.childrenshospital.org

answers.childrenshospital.org/gvhd-abatacept/

Abatacept prevents GVHD after bone marrow transplant

Rates of survival free of severe GVHD were 97.7 percent and 58.7 percent, respectively.

5.

becarispublishing.com

becarispublishing.com/doi/10.57264/cer-2023-0144

Real-world clinical outcomes and rationale for initiating ...

Of 279 patients not in CDAI low disease activity (LDA) or remission at baseline, 24.7% of patients achieved it within 6 months, 56.3% within 12 ...

6.

orenciahcp.com

orenciahcp.com/safety-data.html

Safety Data | ORENCIA® (abatacept)

In placebo-controlled trials, infections were reported in 54% of ORENCIA-treated patients and 48% of placebo-treated patients. The most commonly reported ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10259009/

Safety outcomes in patients with rheumatoid arthritis ...

Data from randomized, controlled clinical trials have shown abatacept to be well tolerated, with adverse event rates similar to those of placebo, and to have a ...

8.

sciencedirect.com

sciencedirect.com/science/article/pii/S0049017223000823

Malignancy outcomes in patients with rheumatoid arthritis ...

For patients with lymphoma, evidence of a statistically significantly increased risk was noted with abatacept compared with other b/tsDMARDs in one data source, ...

9.

orencia.com

orencia.com/about-orencia

ORENCIA® Side Effects & Rheumatoid Arthritis (RA) ...

Safety data from this trial were consistent with results included in the combined safety profile for ORENCIA shown below.