BGB-11417 for Acute Myeloid Leukemia and Myelodysplastic Syndrome

Recruiting in Palo Alto (17 mi)

+77 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: BeiGene

Must not be taking: B-cell lymphoma-2 inhibitors

Disqualifiers: Acute promyelocytic leukemia, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests a new drug, BGB-11417, alone and with azacitidine, in patients with certain blood cancers to see if it is safe and effective, and to find the best dose.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more details.

What data supports the effectiveness of the drug BGB-11417 for treating Acute Myeloid Leukemia and Myelodysplastic Syndrome?

Research shows that azacitidine, a component of the treatment, is effective for patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Additionally, combining azacitidine with venetoclax, a drug similar to BGB-11417, has improved survival rates in patients with AML. ^{1 2 3 4 5}

Is BGB-11417 (Azacitidine) safe for humans?

Azacitidine, often used with venetoclax, has been studied for safety in patients with acute myeloid leukemia and myelodysplastic syndromes. Common side effects include low blood cell counts, which can lead to infections, anemia (low red blood cells), and bleeding issues. Overall, it is considered safe for use in patients who cannot undergo intensive chemotherapy, but monitoring for these side effects is important. ^{3 4 6 7 8}

What makes the drug BGB-11417 unique for treating acute myeloid leukemia and myelodysplastic syndrome?

BGB-11417, combined with Azacitidine, is unique because it potentially offers a novel mechanism of action or combination that could enhance treatment effectiveness for acute myeloid leukemia and myelodysplastic syndrome, compared to Azacitidine alone, which is already known for prolonging survival in these conditions. ^{4 5 9 10 11}

Research Team

David Simpson, MD

Principal Investigator

BeiGene

Eligibility Criteria

This trial is for adults with certain blood disorders like AML, MDS, or MDS/MPN. They should be relatively active (able to care for themselves), have kidneys and liver working well, and expected to live more than 12 weeks. People can't join if they've had leukemia in the brain, certain other cancers in the last 2 years, specific blood diseases including myelofibrosis or polycythemia vera, or previous treatments with similar drugs.

Inclusion Criteria

I have been diagnosed with AML, MDS, or MDS/MPN and can care for myself.

Adequate organ function defined as: Creatinine clearance ≥ 50 milliliters/minute (mL/min) (or between 30 and 49 mL/min in unfit AML cohort); Adequate liver function; Life expectancy of > 12 weeks; Ability to comply with the requirements of the study.

Exclusion Criteria

My leukemia has spread to my brain or spinal cord.

I haven't had cancer in the last 2 years, except for certain treated early-stage cancers.

I have not taken B-cell lymphoma-2 inhibitors or azacitidine, or I meet the criteria for HMA failure.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BGB-11417 as monotherapy or in combination with azacitidine on a 28-day cycle

24 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• Azacitidine (Epigenetic Modifying Agent)
• BGB-11417 (Epigenetic Modifying Agent)

Trial Overview The study tests BGB-11417 alone and combined with azacitidine to find a safe dose and see how effective it is against acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Posaconazole is also used as part of the treatment regimen.

Participant Groups

Group I: Parts 1 and 2: MDS Cohorts Experimental Treatment 2 Interventions

Participants with MDS will receive BGB-11417 and azacitidine on a 28-day cycle.

Group II: Parts 1 and 2: AML Cohorts Experimental Treatment 2 Interventions

Participants with AML will receive BGB-11417 and azacitidine on a 28-day cycle.

Group III: Part 3: AML and MDS Cohorts Experimental Treatment 3 Interventions

Participants with AML and MDS will receive BGB-11417 and azacitidine on a 28-day cycle. A subset of the participants will receive a modified second cycle of treatment to explore drug-drug interactions (DDI) with posaconazole.

Group IV: Part 3: AML and MDS Cohort Experimental Treatment 1 Intervention

Participants with MDS and R/R AML (China only) will receive BGB-11417 on a 28-day cycle.

Azacitidine is already approved in Canada, Japan for the following indications:

Approved in Canada as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Approved in Japan as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Who Is Running the Clinical Trial?

BeiGene

Lead Sponsor

Trials

216

Recruited

32,500+

Findings from Research

In patients with newly diagnosed unfit acute myeloid leukemia (AML), the combination of azacitidine and venetoclax is a standard first-line treatment.

However, patients with TP53-mutated AML and poor-risk cytogenetics do not benefit from adding venetoclax to azacitidine, suggesting that alternative treatment regimens should be considered for these individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TP53 or Not TP53: That Is the Question. Green, SD., Zeidner, JF.[2023]

In a phase II study involving 60 older or unfit patients with newly diagnosed acute myeloid leukemia (AML), the combination of venetoclax with cladribine and low-dose cytarabine alternating with venetoclax and 5-azacitidine resulted in a high composite complete response rate of 93%.

The treatment showed promising overall survival and disease-free survival rates, with only one death occurring within 4 weeks, indicating that this regimen is effective and has a favorable safety profile for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Study of Venetoclax Added to Cladribine Plus Low-Dose Cytarabine Alternating With 5-Azacitidine in Older Patients With Newly Diagnosed Acute Myeloid Leukemia. Kadia, TM., Reville, PK., Wang, X., et al.[2023]

In a Japanese subgroup of the phase 3 VIALE-A trial, venetoclax-azacitidine significantly improved overall survival rates compared to placebo-azacitidine, with 67% of patients alive at 12 months versus 46% in the placebo group.

The treatment also resulted in a high complete response (CR) and CR with incomplete hematologic recovery (CRi) rate of 67%, while maintaining a safety profile similar to the global study, indicating it is a viable first-line treatment for Japanese patients with acute myeloid leukemia ineligible for intensive chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax plus azacitidine in Japanese patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy. Yamamoto, K., Shinagawa, A., DiNardo, CD., et al.[2023]

The Vidaza Access Program in Belgium successfully facilitated access to azacitidine treatment for 175 patients with myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelomonocytic leukemia (CMML) by streamlining the approval process for patient dossiers.

Out of the 175 patient dossiers submitted, 163 were approved by Celgene, demonstrating the program's effectiveness in ensuring timely treatment initiation without financial risk to hospitals, which is crucial for patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azacitidine access program for Belgian patients with myelodysplastic syndromes, acute myeloid leukemia or chronic myelomonocytic leukemia. Meers, S., Selleslag, D., Potier, H., et al.[2018]

In the HiDDAV study involving 42 newly diagnosed AML patients, higher doses of venetoclax (600 mg daily) were found to be tolerable but did not show significant clinical improvement compared to the standard 400 mg dose.

The study revealed that using minimal residual disease (MRD) status to guide the discontinuation of azacitidine did not lead to better outcomes in terms of duration of response or overall survival, suggesting that alternative strategies are needed to optimize treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Higher-dose venetoclax with measurable residual disease-guided azacitidine discontinuation in newly diagnosed acute myeloid leukemia. Gutman, JA., Winters, A., Kent, A., et al.[2023]

The combination of azacitidine and venetoclax is safe and well-tolerated in patients with high-risk myelodysplastic syndromes or chronic myelomonocytic leukaemia, with a recommended phase 2 dose established as azacitidine 75 mg/m2 for 5 days plus venetoclax 400 mg for 14 days.

The treatment showed a high overall response rate of 87% among the 23 enrolled patients, indicating promising preliminary activity for this combination therapy in treatment-naive and relapsed or refractory cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azacitidine plus venetoclax in patients with high-risk myelodysplastic syndromes or chronic myelomonocytic leukaemia: phase 1 results of a single-centre, dose-escalation, dose-expansion, phase 1-2 study. Bazinet, A., Darbaniyan, F., Jabbour, E., et al.[2022]

In a long-term follow-up study of patients with acute myeloid leukemia (AML), the combination of venetoclax with azacitidine or decitabine showed a high complete remission rate of 71% and 74%, respectively, indicating strong efficacy for patients ineligible for intensive chemotherapy.

The median overall survival for patients treated with venetoclax plus azacitidine was 16.4 months, and 16.2 months for those treated with decitabine, demonstrating that this treatment combination is a viable frontline option for AML patients who cannot undergo more aggressive therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax with azacitidine or decitabine in patients with newly diagnosed acute myeloid leukemia: Long term follow-up from a phase 1b study. Pollyea, DA., Pratz, K., Letai, A., et al.[2021]

In a study of 259 adults with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), the combination of azacitidine (AZA) and vorinostat (VOR) did not improve overall response rates or survival compared to AZA alone, indicating that VOR does not enhance the efficacy of AZA in treating these conditions.

The study identified specific genetic mutations (CDKN2A, IDH1, and TP53) that are associated with poorer overall survival, suggesting that these mutations could help predict patient outcomes and that AZA may work by inducing cell-cycle arrest in affected cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome of Azacitidine Therapy in Acute Myeloid Leukemia Is not Improved by Concurrent Vorinostat Therapy but Is Predicted by a Diagnostic Molecular Signature. Craddock, CF., Houlton, AE., Quek, LS., et al.[2022]

Azacitidine (Vidaza) is the only drug approved in the EU that significantly prolongs survival in adults with high-risk myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML), making it a crucial treatment option for patients not eligible for stem cell transplantation.

The treatment is associated with a lower risk of AML progression and higher rates of remission and blood transfusion independence, while maintaining an acceptable safety profile, with peripheral cytopenias being the most common side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azacitidine: a review of its use in higher-risk myelodysplastic syndromes/acute myeloid leukaemia. Keating, GM.[2021]

References

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

TP53 or Not TP53: That Is the Question. [2023]

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

Phase II Study of Venetoclax Added to Cladribine Plus Low-Dose Cytarabine Alternating With 5-Azacitidine in Older Patients With Newly Diagnosed Acute Myeloid Leukemia. [2023]

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

Venetoclax plus azacitidine in Japanese patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy. [2023]

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

Azacitidine access program for Belgian patients with myelodysplastic syndromes, acute myeloid leukemia or chronic myelomonocytic leukemia. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Impact of performance status and transfusion dependency on outcome of patients with myelodysplastic syndrome, acute myeloid leukemia and chronic myelomonocytic leukemia treated with azacitidine (PIAZA study). [2019]

6. Italy pubmed.ncbi.nlm.nih.gov

Higher-dose venetoclax with measurable residual disease-guided azacitidine discontinuation in newly diagnosed acute myeloid leukemia. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Azacitidine plus venetoclax in patients with high-risk myelodysplastic syndromes or chronic myelomonocytic leukaemia: phase 1 results of a single-centre, dose-escalation, dose-expansion, phase 1-2 study. [2022]

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

Venetoclax with azacitidine or decitabine in patients with newly diagnosed acute myeloid leukemia: Long term follow-up from a phase 1b study. [2021]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Azacitidine: A Review in Myelodysplastic Syndromes and Acute Myeloid Leukaemia. [2022]

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

Outcome of Azacitidine Therapy in Acute Myeloid Leukemia Is not Improved by Concurrent Vorinostat Therapy but Is Predicted by a Diagnostic Molecular Signature. [2022]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Azacitidine: a review of its use in higher-risk myelodysplastic syndromes/acute myeloid leukaemia. [2021]