CC-91633 for Leukemia

No longer recruiting at 39 trial locations

Overseen By BMS Study Connect Contact Center www.BMSStudyConnect.com

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Celgene

Must not be taking: Anticoagulants

Disqualifiers: CNS leukemia, Cardiac diseases, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 42 days for dose-limiting toxicity assessment

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, CC-91633 (also known as BMS-986397), to evaluate its safety and effectiveness for certain blood disorders. It targets individuals with either relapsed or refractory acute myeloid leukemia (R/R AML) or higher-risk myelodysplastic syndromes (R/R HR-MDS) who have not responded to existing treatments. The treatment is administered orally, and the trial aims to determine the optimal dose for future studies. Individuals with these conditions who have not found success with other therapies may be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes participants who are on ongoing treatment with certain anticoagulants (blood thinners). It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that CC-91633 is being tested for safety in people with certain blood cancers that haven't responded to other treatments. As this is the first human trial of the drug, the goal is to assess tolerance and determine the appropriate dose.

In this Phase 1 trial, the primary focus is on safety and tolerance. Researchers closely monitor for any side effects and aim to identify a safe dose. They begin with low doses and gradually increase them to determine the maximum amount the body can handle without causing serious side effects.

There is no previous data on CC-91633 for relapsed or refractory acute myeloid leukemia (R/R AML) or higher-risk myelodysplastic syndromes (R/R HR-MDS) because this is the first human test. Therefore, participants will be carefully monitored throughout the study to ensure their safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for relapsed or refractory acute myeloid leukemia (AML) and higher-risk myelodysplastic syndromes (HR-MDS), which often involves chemotherapy or hypomethylating agents, CC-91633 works differently by targeting specific pathways to potentially address resistance seen in these conditions. Researchers are excited because CC-91633 is administered orally, which can be more convenient compared to intravenous treatments. Additionally, the treatment is designed to determine optimal dosing through its unique dose-escalation approach, which may enhance its effectiveness and safety profile. These features make CC-91633 a promising candidate for patients who haven't responded well to existing therapies.

What evidence suggests that CC-91633 might be an effective treatment for relapsed or refractory acute myeloid leukemia and higher-risk myelodysplastic syndromes?

Studies have shown that CC-91633, also known as BMS-986397, is being explored as a potential treatment for certain blood cancers, specifically relapsed or refractory acute myeloid leukemia (R/R AML) and higher-risk myelodysplastic syndromes (R/R HR-MDS). In this trial, participants with R/R AML and R/R HR-MDS will receive CC-91633 to evaluate its safety and efficacy. Research indicates that patients with these conditions often struggle to fully recover with standard treatments. CC-91633 aims to stop cancer cells from growing and spreading by targeting specific pathways in these cells. Although this research remains in the early stages, focusing on these pathways shows promise for this treatment. Initial findings suggest that this approach could lead to better results compared to current treatments. ^{1 2 3 6 7}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

Adults with relapsed or refractory acute myeloid leukemia (R/R AML) or higher-risk myelodysplastic syndromes (R/R HR-MDS), who have not responded to available treatments. They should be in a stable condition, without severe complications like uncontrolled infection/bleeding, and meet specific health criteria such as adequate liver function and no active hepatitis B/C.

Inclusion Criteria

Participant must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted

My leukemia or myelodysplastic syndrome has not improved with treatment.

Participants must satisfy the criteria below to be enrolled in the Dose Escalation (Part A) or the Dose Expansion (Part B) of this study

Exclusion Criteria

Participants with known human immunodeficiency virus infection

I am currently receiving treatment for another cancer besides the one being studied.

I have heart problems that affect my daily activities.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive escalating doses of CC-91633 to determine the maximum tolerated dose and evaluate safety and tolerability

Up to 42 days for dose-limiting toxicity assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 4 years

Expansion

Confirm tolerability of selected doses and evaluate efficacy for further clinical development

Ongoing

What Are the Treatments Tested in This Trial?

Interventions

• CC-91633

Trial Overview The trial is testing CC-91633 (BMS-986397), an oral medication for R/R AML and R/R HR-MDS. It's a Phase 1 study with two parts: dose escalation to find the maximum tolerated dose, followed by expansion to confirm tolerability and assess preliminary efficacy.

How Is the Trial Designed?

Group I: Participants with Relapsed or Refractory Higher-Risk Myelodysplastic Syndromes (HR-MDS) Experimental Treatment 1 Intervention

Part B (expansion part) will confirm tolerability of the selected doses and schedules and evaluate whether efficacy is in a range that warrants further clinical development for R/R HR-MDS participants.

Group II: Participants with Relapsed or Refractory Acute Myeloid Leukemia (R/R AML) Experimental Treatment 1 Intervention

Part B (expansion part) will confirm tolerability of the selected doses and schedules and evaluate whether efficacy is in a range that warrants further clinical development for R/R AML participants.

Group III: Participants with R/R AML and R/R HR-MDS - Part A Experimental Treatment 1 Intervention

Part A (Dose Escalation) of the study will enroll R/R AML (Relapsed or Refractory Acute Myeloid Leukemia) and R/R HR-MDS (Relapsed or Refractory Higher-Risk Myelodysplastic Syndromes) participants and will evaluate the safety and tolerability of escalating doses of CC-91633, administered orally, and determine the maximum tolerated dose (MTD) or preliminary recommended Phase 2 doses (RP2D) and schedule.

Who Is Running the Clinical Trial?

Celgene

Lead Sponsor

Trials

649

Recruited

130,000+

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Jay Backstrom

Celgene

Chief Medical Officer since 2016

MD

Mark Alles

Celgene

Chief Executive Officer since 2016

Bachelor's degree from Lock Haven University of Pennsylvania

Published Research Related to This Trial

In a study of 83 patients with chronic myelogenous leukemia (CML) undergoing bone marrow transplantation (BMT), durable engraftment was achieved in 97% of cases, indicating a high success rate for the procedure.

The overall survival rates were 64% for patients in chronic phase, 53% for those in accelerated phase, and 30% for patients in blast crisis, demonstrating that earlier stages of CML have better outcomes after transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long term follow up after allogeneic stem cell transplantation for chronic myelogenous leukemia. Reiter, E., Greinix, HT., Brugger, S., et al.[2007]

The Philadelphia chromosome, resulting from a specific genetic translocation (t(9;22)), is a key marker for chronic myeloid leukemia (CML) and is linked to a poor prognosis in other leukemias, such as acute lymphoblastic leukemia.

In 80% of CML cases, the disease progresses through clonal evolution, and the emergence of an isochromosome 17q indicates a transition to a more aggressive myeloid blast crisis, highlighting the need for effective treatment strategies beyond palliative care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cytogenetic and clinical features of Philadelphia chromosome positive leukemias]. Becher, R., Kloke, O.[2007]

Infant leukemias, particularly acute lymphoblastic leukemia (ALL), are aggressive and often difficult to treat, with specific genetic abnormalities like the KMT2A-AFF1 fusion indicating a poor prognosis.

Some neonatal leukemias can show spontaneous remission, especially those with the t(8;16) translocation, highlighting the need for international studies to better understand and improve treatment options for these rare conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Acute leukemia of infants and neonates]. Eguchi, M.[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]

In a study of 43 patients with advanced chronic myelogenous leukemia (CML), the type of chemotherapy used for mobilizing peripheral blood stem cells (PBSC) significantly affected the success of harvesting Ph-negative cells, with 'mini-ICE/ICE' yielding better results than '5+2/7+3'.

All 25 patients who underwent PBSC transplantation after successful mobilization engrafted without any transplantation-related mortality, indicating a safe and effective approach for patients not responsive to conventional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome of peripheral blood stem cell mobilization in advanced phases of CML is dependent on the type of chemotherapy applied. Fischer, T., Neubauer, A., Mohm, J., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04951778

Study to Evaluate Safety and Tolerability of CC-91633 ... A Phase 1, open-label, dose escalation and expansion, first-in-human (FIH) clinical study of CC-91633 (BMS-986397) in participants with relapsed or refractory ...

2. bmsstudyconnect.com bmsstudyconnect.com/dk/en/clinical-trials/NCT04951778.html

Study to Evaluate Safety and Tolerability of CC-91633 (BMS ... Study CC-91633-AML-001 is a Phase 1, open-label, dose escalation and expansion, first-in-human (FIH) clinical study of CC-91633 (BMS-986397) ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-08851

Study to Evaluate Safety and Tolerability of CC-91633 ... CC-91633-AML-001 is a Phase 1, open-label, dose escalation and expansion, first-in-human (FIH) clinical study of CC-91633 (BMS-986397) in participants with ...

4. clin.larvol.com clin.larvol.com/trial-detail/NCT04951778

Study to Evaluate Safety and Tolerability of CC-91633 ... Combined complete remission rate (cCRR), is defined as the percent of participants whose best response is complete remission, includes minimal residual disease ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7486485/

Outcomes of patients with relapsed or refractory acute ... With standard therapies for patients with acute myeloid leukemia (AML), many patients either do not achieve complete response (CR) or relapse after CR.

6. withpower.com withpower.com/trial/phase-1-leukemia-myeloid-acute-6-2021-df137

CC-91633 for Leukemia · Info for Participants This trial tests a new drug, CC-91633, for patients with certain blood cancers that haven't responded to other treatments. Researchers will find the safest ...

7. clinicalresearch.com clinicalresearch.com/en/find-trials/Study/NCT04951778

NCT04951778 Study to Evaluate Safety and Tolerability of CC-91633 (BMS-986397) in Participants With Relapsed or Refractory Acute Myeloid Leukemia or Relapsed or Refractory ...