CC-486 + Venetoclax for Acute Myeloid Leukemia

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Daniel Pollyea, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: University of Colorado, Denver

Must be taking: CC-486, Venetoclax

Disqualifiers: Active CNS AML, HIV, Hepatitis, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This is an open label, dose escalation Phase I single institution pilot study for relapsed and refractory AML patients using CC-486 (oral azacitidine) with venetoclax. At the completion of dose escalation and after establishment of the MTD or recommended dose of CC-486 with venetoclax, an expansion phase will commence, using venetoclax with the MTD of CC-486 in relapsed/refractory patients.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the drug combination CC-486 and Venetoclax for treating Acute Myeloid Leukemia?

Venetoclax, when combined with other treatments, has shown promising results for patients with acute myeloid leukemia, especially those who are older or not fit for intensive chemotherapy. Studies have demonstrated improved response rates and overall survival in these patients. ^{1 2 3 4 5}

Is the combination of CC-486 and Venetoclax safe for humans?

Venetoclax, used in combination with other drugs, has been found to have an acceptable safety profile in patients with conditions like chronic lymphocytic leukemia and acute myeloid leukemia. Common side effects include gastrointestinal issues like diarrhea, nausea, and vomiting, as well as blood-related issues like neutropenia (low white blood cell count). ^{1 6 7 8 9}

How is the drug CC-486 + Venetoclax unique for treating acute myeloid leukemia?

The combination of CC-486 and Venetoclax is unique because it offers a new treatment option for older patients or those unable to undergo intensive chemotherapy, using Venetoclax's ability to target cancer cells by inhibiting a protein that helps them survive, combined with CC-486, an oral form of azacitidine, which helps modify the DNA of cancer cells to stop their growth. ^{1 2 3 10 11}

Research Team

Daniel Pollyea, MD

Principal Investigator

University of Colorado, Denver

Eligibility Criteria

This trial is for adults with Acute Myeloid Leukemia (AML) who have already tried at least one treatment. They should expect to live at least 12 weeks, be able to perform daily activities with some limitations (ECOG ≤2), and have good kidney and liver function. Women must be postmenopausal or surgically sterile; men must agree to use contraception. Participants can't join if they have severe heart issues, uncontrolled infections, active CNS leukemia, HIV/hepatitis B/C infection, certain other cancers or are pregnant/breastfeeding.

Inclusion Criteria

Subject must have a projected life expectancy of at least 12 weeks.

I have AML (not APL type) confirmed by WHO criteria and have received at least one treatment.

I am unable to have children due to surgery.

Exclusion Criteria

You are allergic or have a strong reaction to azacitidine or mannitol.

Pregnant or breast-feeding females. A pregnancy test will be obtained at the time of screening.

I do not have any major health issues unrelated to leukemia.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment - Dose Escalation

Participants receive CC-486 and venetoclax with dose escalation to determine the maximum tolerated dose (MTD).

28 days per cycle

Inpatient monitoring for tumor lysis syndrome during initial days

Treatment - Expansion Phase

Participants receive venetoclax with the MTD of CC-486 in relapsed/refractory patients.

28 days per cycle

Bone marrow biopsies on day 28 of every 3rd cycle for responders

Follow-up

Participants are monitored for safety and effectiveness after treatment, with bone marrow biopsies every 6 months after one year.

7 years

Treatment Details

Interventions

• CC-486 (Anti-metabolites)
• Venetoclax (BCL-2 Inhibitor)

Trial Overview The study tests a combination of two drugs: CC-486 (oral azacitidine) and Venetoclax in patients with relapsed/refractory AML. It's an open-label Phase I trial where everyone knows what treatment they're getting. The first part finds the maximum tolerated dose of CC-486 combined with Venetoclax; the second expands this dose in more patients.

Participant Groups

Group I: Dose Expansion Cohort Experimental Treatment 2 Interventions

CC-486 MTD will be determine following the completion of Cohort 1 and Cohort 2 with venetoclax at 400 mg/day PI regimen for 28 days.

Group II: Cohort 2 CC-486 300 mg Experimental Treatment 2 Interventions

CC-486 300 mg will be administered orally on days 1-14 of a 28-day cycle. Venetoclax will be administered days 1-3, with the following schema: 100 mg on day 1, 200 mg on day 2, 400 mg on day 3, and it will be continued at 400mg thereafter until day 28, the completion of cycle 1.

Group III: Cohort 1 CC-486 200 mg Experimental Treatment 2 Interventions

CC-486 200 mg will be administered orally on days 1-14 of a 28-day cycle. Venetoclax will be administered days 1-3, with the following schema: 100 mg on day 1, 200 mg on day 2, 400 mg on day 3, and it will be continued at 400mg thereafter until day 28, the completion of cycle 1.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of Colorado Hospital Aurora, CO

CU Anschutz Medical Campus Aurora, CO

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1842

Patients Recruited

3,028,000+

Bristol-Myers Squibb

Industry Sponsor

Trials

2731

Patients Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Findings from Research

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: Management and Care for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia . Brumbaugh Paradis, H., Alter, D., Llerandi, D.[2018]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Why are hypomethylating agents or low-dose cytarabine and venetoclax so effective? Pollyea, DA., Jordan, CT.[2020]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outpatient initiation of venetoclax in patients with acute myeloid leukemia. Palmer, S., Patel, A., Wang, C., et al.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax plus low-dose cytarabine in patients with newly diagnosed acute myeloid leukemia ineligible for intensive chemotherapy: an expanded access study in Japan. Asada, N., Ando, J., Takada, S., et al.[2023]

Venetoclax has significantly improved treatment outcomes for elderly and unfit patients with acute myeloid leukemia, but resistance to the drug remains a significant challenge.

The study by Bhatt et al. identifies a general mechanism for the development of resistance to venetoclax and suggests potential treatment strategies for managing venetoclax-resistant cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mitochondria in Their Prime Drive Venetoclax Response in Acute Myeloid Leukemia. Kriegbaum, MC., Wennerberg, K.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BCL2 Inhibition by Venetoclax: Targeting the Achilles' Heel of the Acute Myeloid Leukemia Stem Cell? Pullarkat, VA., Newman, EM.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Practical Management of the Venetoclax-Treated Patient in Chronic Lymphocytic Leukemia and Acute Myeloid Leukemia. Waggoner, M., Katsetos, J., Thomas, E., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1b study of venetoclax and alvocidib in patients with relapsed/refractory acute myeloid leukemia. Jonas, BA., Hou, JZ., Roboz, GJ., et al.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced duration and dosage of venetoclax is efficient in newly diagnosed patients with acute myeloid leukemia. Cui, J., Chen, X., Li, C., et al.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax in combination with azacitidine in Japanese patients with acute myeloid leukaemia: phase 1 trial findings. Taniguchi, S., Yamauchi, T., Choi, I., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax-based combinations for acute myeloid leukemia: optimizing their use in Latin-America. Gómez-De León, A., Demichelis-Gómez, R., Pinedo-Rodríguez, A., et al.[2022]

References

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

Venetoclax: Management and Care for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia . [2018]

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

Why are hypomethylating agents or low-dose cytarabine and venetoclax so effective? [2020]

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

Outpatient initiation of venetoclax in patients with acute myeloid leukemia. [2023]

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

Venetoclax plus low-dose cytarabine in patients with newly diagnosed acute myeloid leukemia ineligible for intensive chemotherapy: an expanded access study in Japan. [2023]

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

Mitochondria in Their Prime Drive Venetoclax Response in Acute Myeloid Leukemia. [2021]

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

BCL2 Inhibition by Venetoclax: Targeting the Achilles' Heel of the Acute Myeloid Leukemia Stem Cell? [2021]

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

Practical Management of the Venetoclax-Treated Patient in Chronic Lymphocytic Leukemia and Acute Myeloid Leukemia. [2022]

8. England pubmed.ncbi.nlm.nih.gov

A phase 1b study of venetoclax and alvocidib in patients with relapsed/refractory acute myeloid leukemia. [2023]

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

Reduced duration and dosage of venetoclax is efficient in newly diagnosed patients with acute myeloid leukemia. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Venetoclax in combination with azacitidine in Japanese patients with acute myeloid leukaemia: phase 1 trial findings. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Venetoclax-based combinations for acute myeloid leukemia: optimizing their use in Latin-America. [2022]