What is the mechanism of action of this treatment?

Common treatments for Acute Myeloid Leukemia (AML) include hypomethylating agents like azacitidine and decitabine, which work by inhibiting DNA methylation, thereby reactivating tumor suppressor genes and inducing cancer cell death. Targeted therapies, such as FLT3 inhibitors, focus on specific genetic mutations within AML cells, blocking signals that promote cancer cell proliferation. Growth factor inhibitors aim to reduce the autonomous growth of AML cells by targeting cytokines and growth factors that the cancer cells produce. These mechanisms are crucial for AML patients as they offer more personalized and potentially effective treatment options, especially for those with specific genetic profiles or those who are refractory to conventional chemotherapy.

What side effects are associated with this type of intervention?

Common treatments for Acute Myeloid Leukemia (AML) include hypomethylating agents such as azacitidine and decitabine, which are associated with side effects like cytopenias, febrile neutropenia, and gastrointestinal symptoms (diarrhea, nausea, vomiting). Other targeted therapies, such as IDH inhibitors and gemtuzumab ozogamicin, can cause neutropenia, liver enzyme abnormalities, and infusion-related reactions. Overall, these treatments often lead to hematologic toxicities and require careful monitoring and supportive care.

What prior FDA approvals exist?

The FDA has approved several treatments for Acute Myeloid Leukemia (AML), including hypomethylating agents like azacitidine and decitabine, which are used for patients unfit for intensive chemotherapy. Venetoclax, often combined with azacitidine or decitabine, has also been approved for newly diagnosed AML ineligible for intensive chemotherapy. Additionally, gemtuzumab ozogamicin, a CD33-directed antibody-drug conjugate, is approved for certain AML patients. Oral azacitidine (CC-486) is approved for maintenance therapy post-remission. These treatments reflect a trend towards targeted and less intensive therapies, similar to the investigational agent CC-91633 (BMS-986397).

What other types of research exist?

Promising novel alternatives to CC-91633 for AML patients include: 1) PO-6, a CD123-targeted therapeutic peptide delivered via a micellar system, which prolongs survival by interfering with the CD123/IL-3 axis. 2) AMG 553, a chimeric antigen receptor T-cell therapy targeting FLT3, showing targeted cytotoxicity against FLT3-positive AML cells. 3) SH1573, a mutant IDH2 inhibitor that reduces 2-HG production and promotes differentiation of AML cells. These alternatives offer different mechanisms of action and have shown efficacy in preclinical or early clinical studies.

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CC-91633 for Leukemia

Phase 1

Recruiting

Research Sponsored by Celgene

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Relapsed or refractory acute myeloid leukemia (R/R AML) and relapsed or refractory higher-risk myelodysplastic syndromes (R/R HR-MDS) as defined by the World Health Organization (WHO) criteria who have failed or are ineligible for all available therapies which may provide clinical benefit

Participant has Eastern Cooperative Oncology Group Performance Status of 0 to 2

Must not have

Participants with history of concurrent second cancers requiring active, ongoing systemic treatment

Participants with impaired cardiac function or clinically significant cardiac diseases

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 4 years

Awards & highlights

Summary

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 dose by increasing it over time and checking for side effects and effectiveness.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

While specific side effects of CC-91633 are not listed here, common ones for cancer drugs may include nausea, fatigue, risk of infection due to low blood cell counts, liver issues, diarrhea or allergic reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My leukemia or myelodysplastic syndrome has not improved with treatment.

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I can take care of myself and am up and about more than half of my waking hours.

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I am 18 years old or older.

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My liver tests are within the normal range, or slightly above if due to my leukemia.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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I have heart problems that affect my daily activities.

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I have severe diarrhea, vomiting, or issues absorbing medication.

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I have been diagnosed with acute promyelocytic leukemia.

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I have an ongoing hepatitis B or C infection.

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I am currently on long-term blood thinners.

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I have or might have leukemia in my brain or spinal cord.

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I do not have severe, life-threatening complications from leukemia like uncontrolled infection or bleeding.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 4 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 4 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 4 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Dose-limiting Toxicity (DLT)

Incidence of Adverse Events (AEs)

Maximum Tolerated Dose (MTD)

Secondary study objectives

CC-2004772 Pharmacokinetics - AUC(0-T)

CC-2004772 Pharmacokinetics - AUC(TAU)

CC-2004772 Pharmacokinetics - CLT/F

+27 more

Trial Design

3Treatment groups

Experimental Treatment

Group I: Participants with Relapsed or Refractory Higher-Risk Myelodysplastic Syndromes (HR-MDS)Experimental Treatment1 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 Treatment1 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 AExperimental Treatment1 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.

0 / 12Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Acute Myeloid Leukemia (AML) include hypomethylating agents like azacitidine and decitabine, which work by inhibiting DNA methylation, thereby reactivating tumor suppressor genes and inducing cancer cell death. Targeted therapies, such as FLT3 inhibitors, focus on specific genetic mutations within AML cells, blocking signals that promote cancer cell proliferation. Growth factor inhibitors aim to reduce the autonomous growth of AML cells by targeting cytokines and growth factors that the cancer cells produce. These mechanisms are crucial for AML patients as they offer more personalized and potentially effective treatment options, especially for those with specific genetic profiles or those who are refractory to conventional chemotherapy.

Molecular targets for the treatment of AML in the forthcoming 5th World Health Organization Classification of Haematolymphoid Tumours.Epigenetic deregulation in myeloid malignancies.Emerging Epigenetic Therapeutic Targets in Acute Myeloid Leukemia.

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Who is running the clinical trial?

CelgeneLead Sponsor

645 Previous Clinical Trials

130,369 Total Patients Enrolled

Tim Campbell, MD, PhDStudy DirectorCelgene

Bristol-Myers SquibbStudy DirectorBristol-Myers Squibb

1,559 Previous Clinical Trials

3,383,536 Total Patients Enrolled

Media Library

CC-91633 (Other) Clinical Trial Eligibility Overview. Trial Name: NCT04951778 — Phase 1

$Acute Myeloid Leukemia Research Study Groups: Participants with Relapsed or Refractory Higher-Risk Myelodysplastic Syndromes (HR-MDS), Participants with Relapsed or Refractory Acute Myeloid Leukemia (R/R AML), Participants with R/R AML and R/R HR-MDS - Part A$