CC-96191 for Acute Myeloid Leukemia

Recruiting at 29 trial locations

Overseen By BMS Study Connect Contact Center http://www.bmsstudyconnect.com

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Celgene

Must not be taking: Systemic immunosuppressants

Disqualifiers: CNS leukemia, HIV, Hepatitis, others

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

Compensation: Varies

Number of Visits: 2

80 Participants Needed

Trial Summary

What is the purpose of this trial?

This Phase 1, clinical study of CC-96191 will explore the safety, tolerability and preliminary biological and clinical activity of CC-96191 as a single-agent in the setting of Relapsed or refractory acute myeloid leukemia (R/R AML). The dose escalation (Part A) of the study will explore escalating intravenous doses of CC-96191 to estimate the MTD and/or RP2D of CC-96191 as monotherapy. The expansion (Part B), will further evaluate the safety and efficacy of CC-96191 administered at or below the MTD in one or more expansion cohorts in order to determine the RP2D.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have received systemic anticancer therapy or radiotherapy within 28 days before starting the study treatment, except for hydroxyurea to control leukemia blasts.

What data supports the idea that CC-96191 for Acute Myeloid Leukemia is an effective drug?

The available research does not provide specific data on the effectiveness of CC-96191 for treating Acute Myeloid Leukemia. Instead, it highlights other drugs and treatments that have shown effectiveness, such as the combination of azacitidine with ivosidenib, which tripled overall survival and increased complete remission rates in patients. Other treatments like venetoclax with azacitidine are also mentioned as effective for certain patient groups. However, there is no direct mention of CC-96191 in the context of these studies. ^{1 2 3 4 5}

What safety data is available for the treatment CC-96191 in acute myeloid leukemia?

The provided research does not contain any safety data specifically for the treatment CC-96191, CC 96191, CC96191, or DF-2001 in acute myeloid leukemia. The studies mentioned focus on other treatments such as CC-486, midostaurin, tipifarnib, glasdegib, and FLAG-idarubicin, none of which are related to CC-96191 or its other names. ^{6 7 8 9 10}

Is the drug CC-96191 a promising treatment for Acute Myeloid Leukemia?

The information provided does not specifically mention CC-96191, so we cannot determine if it is a promising treatment for Acute Myeloid Leukemia based on the given research articles. ^{4 11 12 13 14}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

Adults (≥18 years) with relapsed or refractory acute myeloid leukemia that is CD33 positive. They must have an ECOG performance status of 0 or 1, agree to use contraception, and have no available therapies left. Excluded are those with recent transplants, CNS leukemia, active infections like HIV or hepatitis B/C, heart issues, ongoing cancer treatments other than AML, and unresolved toxicities from past treatments.

Inclusion Criteria

Participant must understand and voluntarily sign an informed consent form (ICF) prior to any study-related assessments/procedures being conducted.

I am fully active or restricted in physically strenuous activity but can do light work.

I will use birth control or practice abstinence during and after the study.

Exclusion Criteria

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

I haven't had cancer treatment or radiotherapy in the last 28 days or less than 5 half-lives of the drug, except for hydroxyurea.

I am diagnosed or suspected to have a specific type of leukemia (APL).

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation (Part A)

Exploration of escalating intravenous doses of CC-96191 to estimate the MTD and/or RP2D as monotherapy

4-6 weeks

Weekly visits for dose escalation

Expansion (Part B)

Evaluation of safety and efficacy of CC-96191 at or below the MTD in expansion cohorts

28-day cycles

Monthly visits for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 35 days after last dose

2 visits (in-person)

Treatment Details

Interventions

• CC-96191

Trial Overview The trial tests CC-96191 in adults with acute myeloid leukemia that's come back or hasn't responded to treatment. It has two parts: Part A finds the highest dose patients can take without bad side effects; Part B checks how well it works at this dose.

Participant Groups

Group I: CC-96191 Experimental Treatment 1 Intervention

CC-96191 will be administered intravenously on a 28-day Cycle

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

Findings from Research

A phase III study demonstrated that combining azacitidine with the IDH1 inhibitor ivosidenib significantly improves treatment outcomes for patients with acute myeloid leukemia who cannot undergo intensive chemotherapy.

The combination therapy tripled overall survival rates and enhanced complete remission and event-free survival compared to azacitidine alone, indicating a substantial efficacy boost from this drug pairing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ivosidenib Boosts OS with Azacitidine in AML. [2022]

Glasdegib, a smoothened (SMO) inhibitor, has been approved by the FDA and EMA for treating naïve acute myeloid leukemia (AML) patients who are not suitable for intensive chemotherapy, showing efficacy in controlling the disease when combined with low-dose cytarabine.

Clinical studies indicate that glasdegib has a favorable safety profile and may enhance the effectiveness of both traditional chemotherapy and biological treatments, such as FLT3 inhibitors, although further research is needed to identify which patients will benefit the most.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glasdegib for the treatment of acute myeloid leukemia. Bruzzese, A., Martino, EA., Labanca, C., et al.[2023]

Recent advancements in drug approvals for acute myeloid leukemia (AML) have significantly improved treatment options, particularly for patients with specific genetic abnormalities, such as core-binding factor and FLT3.

For newly diagnosed patients who are considered 'unfit' for traditional chemotherapy, a combination of venetoclax and azacitidine is recommended, highlighting the need for ongoing research to better define patient fitness for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Advances in First-Line Management of Acute Myeloid Leukemia. Pollyea, DA.[2020]

Since 2017, the FDA has approved nine new agents for treating acute myeloid leukemia (AML), marking significant progress in AML therapy after decades of slow advancement.

Specific treatments for subsets of AML, such as all-trans retinoic acid and arsenic trioxide for acute promyelocytic leukemia, have led to impressive 10-year survival rates of over 80%, demonstrating the efficacy of targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute myeloid leukemia: Treatment and research outlook for 2021 and the MD Anderson approach. Kantarjian, HM., Kadia, TM., DiNardo, CD., et al.[2021]

Bortezomib combined with chemotherapy was found to be tolerable for pediatric patients with relapsed acute myeloid leukemia (AML), with complete response rates of 29% for those with lower prior anthracycline exposure and 43% for those with higher exposure.

Despite the tolerability, the treatment regimens did not meet the predetermined efficacy thresholds for continued patient enrollment, indicating that while bortezomib may help deplete leukemia initiating cells, it may not significantly improve overall response rates in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 2 study of bortezomib combined with either idarubicin/cytarabine or cytarabine/etoposide in children with relapsed, refractory or secondary acute myeloid leukemia: a report from the Children's Oncology Group. Horton, TM., Perentesis, JP., Gamis, AS., et al.[2021]

The QUAZAR AML Maintenance trial is a Phase III study investigating the efficacy of CC-486, an oral formulation of azacitidine, in prolonging overall survival for older patients (aged ≥55) with acute myeloid leukemia (AML) in first complete remission.

The trial will assess not only overall survival but also relapse-free survival, safety, and quality of life, aiming to determine if CC-486 can improve outcomes for this patient population compared to a placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design of the randomized, Phase III, QUAZAR AML Maintenance trial of CC-486 (oral azacitidine) maintenance therapy in acute myeloid leukemia. Roboz, GJ., Montesinos, P., Selleslag, D., et al.[2018]

Midostaurin, a multikinase inhibitor, was found to have a manageable safety profile in a study of 103 patients with FLT3 mutation-positive acute myeloid leukemia, with no new safety events reported during treatment.

The treatment showed promising outcomes, including high rates of transplant success and low relapse rates during maintenance therapy, indicating its efficacy when combined with chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated safety of midostaurin plus chemotherapy in newly diagnosed FLT3 mutation-positive acute myeloid leukemia: the RADIUS-X expanded access program. Roboz, GJ., Strickland, SA., Litzow, MR., et al.[2021]

In a phase 3 study involving 457 elderly patients with acute myeloid leukemia, tipifarnib did not significantly improve overall survival compared to best supportive care, with median survival times of 107 days for tipifarnib and 109 days for supportive care.

The complete response rate for tipifarnib was only 8%, and while it had a similar duration of response as seen in previous studies, it was associated with a higher incidence of severe side effects, such as infections and febrile neutropenia, compared to best supportive care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized phase 3 study of tipifarnib compared with best supportive care, including hydroxyurea, in the treatment of newly diagnosed acute myeloid leukemia in patients 70 years or older. Harousseau, JL., Martinelli, G., Jedrzejczak, WW., et al.[2021]

Glasdegib, an oral Hedgehog pathway inhibitor, significantly improves survival rates in patients with untreated acute myeloid leukemia (AML) when combined with low-dose cytarabine compared to low-dose cytarabine alone.

The BRIGHT AML 1019 trial is a Phase III study evaluating glasdegib in combination with standard chemotherapy regimens, focusing on overall survival and other important outcomes in adults with untreated AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glasdegib plus intensive/nonintensive chemotherapy in untreated acute myeloid leukemia: BRIGHT AML 1019 Phase III trials. Cortes, JE., Dombret, H., Merchant, A., et al.[2020]

The FLAG-IDA chemotherapy regimen was administered to seven children with refractory acute myeloid leukemia (AML), and while it was tolerable with no early deaths, the efficacy remains uncertain due to high relapse rates and limited patient numbers.

Hematological toxicity was common among patients, with one case of severe non-hematological toxicity (bacterial meningitis), highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fludarabine, cytarabine, granulocyte colony-stimulating factor and idarubicin for relapsed childhood acute myeloid leukemia. Nakayama, H., Tomizawa, D., Tanaka, S., et al.[2018]

In a study of 61 adult patients with core binding factor acute myeloid leukemia (CBF AML), the combination of dasatinib with chemotherapy resulted in a high complete remission rate of 90% and a low relapse rate of only 16% after a median follow-up of 45 months.

Dasatinib was found to be safe with no unexpected toxicities, and it provided comparable outcomes for patients with mutated KIT genes, suggesting it may mitigate the negative effects of this mutation on treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of dasatinib with chemotherapy in previously untreated core binding factor acute myeloid leukemia: CALGB 10801. Marcucci, G., Geyer, S., Laumann, K., et al.[2022]

In a study of 70 patients with core-binding factor acute myeloid leukaemia (CBF AML), age and a white blood cell count greater than 40 were identified as significant risk factors for poorer overall survival and higher relapse rates.

Consolidation treatment with more than three cycles of intermediate- to high-dose cytarabine was found to improve overall survival and relapse-free survival, highlighting its importance in the treatment regimen for CBF AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic markers in core-binding factor AML and improved survival with multiple consolidation cycles of intermediate-/high-dose cytarabine. Prabahran, A., Tacey, M., Fleming, S., et al.[2019]

In a study of 52 elderly patients with newly diagnosed acute myeloid leukemia (AML), a high mutation frequency of 98.1% was observed, with specific mutations like DNMT3A and TET2 being more common as age increased, indicating important molecular characteristics for diagnosis and treatment.

Among 39 patients treated with DCAG chemotherapy, a complete remission rate of 71.8% was achieved, suggesting that this treatment is effective for elderly AML patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Molecular Features and Clinical Significance of Acute Myeloid Leukemia in Elderly Patients]. Wang, BH., Guan, W., Lyu, N., et al.[2021]

In a study of 19 patients over 70 years old with acute myeloid leukemia, those who received a priming regimen of chemotherapy had a significantly longer median survival time of 11 months compared to just 2 months for those receiving best supportive treatment.

The study found a complete response rate of 46.6% and an overall response rate of 73% after 2 cycles of induction chemotherapy, indicating that the priming regimen is both effective and well-tolerated in older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical Analysis of Priming Regimen for Treatment of Acute Myeloid Leukemia (Non-APL) Patients Aged over 70 Years]. Guo, ZX., Liu, L., Ren, XH., et al.[2018]

References

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

Ivosidenib Boosts OS with Azacitidine in AML. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Glasdegib for the treatment of acute myeloid leukemia. [2023]

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

Therapeutic Advances in First-Line Management of Acute Myeloid Leukemia. [2020]

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

Acute myeloid leukemia: Treatment and research outlook for 2021 and the MD Anderson approach. [2021]

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

A Phase 2 study of bortezomib combined with either idarubicin/cytarabine or cytarabine/etoposide in children with relapsed, refractory or secondary acute myeloid leukemia: a report from the Children's Oncology Group. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Design of the randomized, Phase III, QUAZAR AML Maintenance trial of CC-486 (oral azacitidine) maintenance therapy in acute myeloid leukemia. [2018]

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

Updated safety of midostaurin plus chemotherapy in newly diagnosed FLT3 mutation-positive acute myeloid leukemia: the RADIUS-X expanded access program. [2021]

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

A randomized phase 3 study of tipifarnib compared with best supportive care, including hydroxyurea, in the treatment of newly diagnosed acute myeloid leukemia in patients 70 years or older. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Glasdegib plus intensive/nonintensive chemotherapy in untreated acute myeloid leukemia: BRIGHT AML 1019 Phase III trials. [2020]

10. Australia pubmed.ncbi.nlm.nih.gov

Fludarabine, cytarabine, granulocyte colony-stimulating factor and idarubicin for relapsed childhood acute myeloid leukemia. [2018]

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

Combination of dasatinib with chemotherapy in previously untreated core binding factor acute myeloid leukemia: CALGB 10801. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Prognostic markers in core-binding factor AML and improved survival with multiple consolidation cycles of intermediate-/high-dose cytarabine. [2019]

13. China pubmed.ncbi.nlm.nih.gov

[Molecular Features and Clinical Significance of Acute Myeloid Leukemia in Elderly Patients]. [2021]

14. China pubmed.ncbi.nlm.nih.gov

[Clinical Analysis of Priming Regimen for Treatment of Acute Myeloid Leukemia (Non-APL) Patients Aged over 70 Years]. [2018]