40 Participants Needed

Venetoclax Combination Therapy for Acute Myeloid Leukemia

AK
Overseen ByAmberley Kemic, RN
Age: < 65
Sex: Any
Trial Phase: Phase 1
Sponsor: Medical College of Wisconsin
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

The investigator is testing the addition of venetoclax to 5-azacitidine and vorinostat followed by standard chemotherapy to enhance treatment response in AML patients.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, if you are taking strong or moderate CYP3A4 inhibitors or P-glycoprotein inhibitors, your venetoclax dose may need to be adjusted. It's best to discuss your current medications with the study team.

What data supports the effectiveness of the drug combination therapy for acute myeloid leukemia?

Research shows that combining venetoclax with azacitidine improves remission rates and survival in patients with acute myeloid leukemia compared to azacitidine alone. Additionally, the combination of venetoclax with nucleoside analogs like low-dose cytarabine has led to significant response and survival outcomes in these patients.12345

Is Venetoclax combination therapy safe for treating acute myeloid leukemia?

Venetoclax combination therapy, often used with azacitidine, has shown acceptable safety in treating acute myeloid leukemia (AML), with common side effects including low blood cell counts (neutropenia, thrombocytopenia, and anemia). While some patients experience serious infections, the treatment is generally tolerable, especially when doses are managed carefully.678910

What makes the venetoclax combination therapy unique for treating acute myeloid leukemia?

The venetoclax combination therapy for acute myeloid leukemia is unique because it combines venetoclax with other drugs like azacitidine, cytarabine, and fludarabine, which have different mechanisms of action. This combination has shown improved response and survival rates compared to using azacitidine alone, especially in older or unfit patients.134711

Research Team

MB

Michael Burke, MD

Principal Investigator

Medical College of Wisconsin

Eligibility Criteria

This trial is for AML patients who've relapsed or didn't respond to initial treatments. They must have recovered from previous therapies, have no severe infections or GVHD if post-transplant, and meet specific organ function criteria. Pregnant women can't participate, and contraception is required for those of childbearing potential.

Inclusion Criteria

My cancer has returned after treatment or did not respond to initial treatments.
My AML is detectable in my bone marrow.
My kidney and liver tests are within normal ranges.
See 10 more

Exclusion Criteria

Significant concurrent disease, illness, psychiatric disorder, or social issue that would compromise patient safety or compliance with the protocol treatment or procedures, interfere with consent, study participation, follow up, or interpretation of study results
Patients with a known allergy to any of the drugs used in the study
Patients with any positive fungal culture within 30 days prior to enrollment or evidence of disseminated fungal disease
See 3 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive venetoclax, azacitidine, and vorinostat followed by standard chemotherapy over two 35-day cycles

10 weeks
Multiple visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

42 months

Treatment Details

Interventions

  • Azacitadine
  • Cytarabine
  • Filgrastim
  • Fludarabine
  • Venetoclax
  • Vorinostat
Trial Overview The study tests adding venetoclax to azacitidine and vorinostat before standard chemo in AML patients. The goal is to improve treatment response by combining these drugs with chemotherapy agents like cytarabine and fludarabine.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: AML without Down SyndromeExperimental Treatment6 Interventions
The subject receives 2 courses of therapy approximately 35 days each. Venetoclax: Days 1-14 Azacitidine and Vorinostat: Days 1-5 Filgrastim Days: 5 start and continue until post-nadir ANC \> 500 cells/mm3 Fludarabine and Cytarabine Days 6 - 10 IT Cytarabine Day 0 or 1, optional between day 35 and 42
Group II: AML with Down SyndromeExperimental Treatment6 Interventions
The subject receives 2 courses of therapy approximately 35 days each. Venetoclax: Days 1-14 Azacitidine and Vorinostat: Days 1-5 Filgrastim Days: 5 start and continue until post-nadir ANC \> 500 cells/mm3 Fludarabine and Cytarabine Days 6 - 10 IT Cytarabine Day 0 or 1, optional between day 35 and 42

Azacitadine is already approved in United States, European Union for the following indications:

๐Ÿ‡บ๐Ÿ‡ธ
Approved in United States as Vidaza for:
  • Myelodysplastic Syndrome
  • Acute Myeloid Leukemia
๐Ÿ‡ช๐Ÿ‡บ
Approved in European Union as Vidaza for:
  • Myelodysplastic Syndrome
  • Acute Myeloid Leukemia
  • Juvenile Myelomonocytic Leukemia

Find a Clinic Near You

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials
645
Recruited
1,180,000+

Findings from Research

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.
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.
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 combination of venetoclax with hypomethylating agents (HMA) has significantly improved survival rates in patients with acute myeloid leukemia (AML), as demonstrated in a phase 3 study.
Venetoclax is also safe when added to standard intensive regimens, leading to high remission rates and measurable residual disease negativity in both newly diagnosed and relapsed/refractory AML patients.
Venetoclax in combination with nucleoside analogs in acute myelogenous leukemia.Ball, BJ., Koller, PB., Pullarkat, V.[2023]

References

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]
Venetoclax plus azacitidine in Japanese patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy. [2023]
Venetoclax in combination with nucleoside analogs in acute myelogenous leukemia. [2023]
TP53 or Not TP53: That Is the Question. [2023]
Impact of FLT3 Mutation on Outcomes after Venetoclax and Azacitidine for Patients with Treatment-Naรฏve Acute Myeloid Leukemia. [2023]
[Safety and the Short-Term Efficacy of Venetoclax Combined with Azacitidine Followed by Cladribine in Children with Refractory/Relapsed Acute Myeloid Leukemia]. [2023]
Venetoclax-based combinations for acute myeloid leukemia: optimizing their use in Latin-America. [2022]
Optimizing venetoclax dose in combination with low intensive therapies in elderly patients with newly diagnosed acute myeloid leukemia: An exposure-response analysis. [2020]
[Short-term efficacy of venetoclax combined with azacitidine in acute myeloid leukemia: a single-institution experience]. [2022]
[Efficacy of venetoclax combined azacitidine in newly diagnosed acute myeloid leukemia unfit for standard chemotherapy: a single center experience]. [2023]
SARS-CoV-2 Infection in Patients Treated with Azacitidine and Venetoclax for Acute Leukemia: A Report of a Case Series Treated in a Single Institution. [2023]
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