116 Participants Needed

Venetoclax + Azacitidine for Myelodysplastic Syndrome

Age: 18+
Sex: Any
Trial Phase: Phase 1 & 2
Sponsor: M.D. Anderson Cancer Center
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This phase I/II trial studies the side effects and best dose of venetoclax when given together with azacitidine in treating patients with high-risk myelodysplastic syndrome that has come back (recurrent) or does not respond to treatment (refractory). Drugs used in chemotherapy, such as venetoclax and azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

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

The trial protocol does not specify if you need to stop taking your current medications. However, hydroxyurea is allowed to lower white cell count before starting venetoclax.

What safety data exists for Venetoclax in humans?

In a study involving Venetoclax for a specific type of blood disorder, serious side effects were reported in 19% of patients, with 7% experiencing infections. This suggests that while Venetoclax can be effective, it may also lead to significant adverse effects in some individuals.12345

How is the drug combination of Venetoclax and Azacitidine unique for treating myelodysplastic syndrome?

The combination of Venetoclax and Azacitidine is unique for treating myelodysplastic syndrome because it offers a new option for patients who have not responded to previous treatments, providing meaningful benefits like improved blood counts and independence from blood transfusions, which are not standard outcomes with existing therapies.678910

What data supports the effectiveness of the drug combination Venetoclax and Azacitidine for Myelodysplastic Syndrome?

Research shows that the combination of Venetoclax and Azacitidine has been effective in treating acute myeloid leukemia, improving remission rates and survival. In patients with relapsed or refractory myelodysplastic syndromes, this combination has shown promising results, including complete remission and improved overall survival.6791011

Who Is on the Research Team?

Guillermo Garcia-Manero | MD Anderson ...

Guillermo Garcia-Manero

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with high-risk myelodysplastic syndrome that's either come back or isn't responding to treatment. They should have normal bilirubin and creatinine levels, not be pregnant or breastfeeding, and agree to use contraception. People who've had BCL2 inhibitor therapy or have low-risk MDS aren't eligible.

Inclusion Criteria

Alanine aminotransferase (ALT) < 4 x ULN unless considered due to leukemic involvement
For phase II, patients will be divided into 2 cohorts: Cohort A: patients with HMA-naive high-risk MDS (Int-2 or high risk by the IPSS with overall score >= 1.5) with excess blasts > 5%. Cohort B: patients with relapsed/refractory MDS post-HMA failure (defined as prior receipt of 4 cycles of HMA therapy with failure to attain a response, or progression of disease or relapse at any time after prior response to HMA therapy) with > 5% blasts are eligible. Note: Patients with chronic myelomonocytic leukemia (CMML) and therapy-related MDS are eligible. Hydroxyurea is allowed to lower the white cell count =< 10,000/ul prior to initiation of venetoclax
Total bilirubin < 3 x upper limit of normal (ULN) unless increase is due to Gilbert's disease or leukemic involvement
See 5 more

Exclusion Criteria

My MDS is classified as low or intermediate-1 risk.
I have cognitive impairment.
I have previously received BCL2 inhibitor therapy.
See 1 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive venetoclax orally once daily on days 1-7 or 1-14 and azacitidine subcutaneously or intravenously over 15 minutes on days 1-5. Cycles repeat every 4-8 weeks in the absence of disease progression or unacceptable toxicity.

4-8 weeks per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 30 days and then every 3-6 months for up to 5 years.

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

  • Azacitidine
  • Venetoclax
Trial Overview The trial is testing the combination of two chemotherapy drugs, Venetoclax and Azacitidine, to find the safest dose and see how well they work together in treating patients with aggressive forms of myelodysplastic syndrome.
How Is the Trial Designed?
1Treatment groups
Experimental Treatment
Group I: Treatment (venetoclax, azacitidine)Experimental Treatment2 Interventions
Patients receive venetoclax orally PO QD on days 1-7 or 1-14 and azacitidine SC or IV over 15 minutes on days 1-5. Cycles repeat every 4-8 weeks in the absence of disease progression or unacceptable toxicity.

Azacitidine is already approved in European Union, United States, Canada, Japan for the following indications:

πŸ‡ͺπŸ‡Ί
Approved in European Union as Vidaza for:
  • Acute myeloid leukemia
  • Chronic myelomonocytic leukemia
  • Myelodysplastic syndromes
πŸ‡ΊπŸ‡Έ
Approved in United States as Vidaza for:
  • Myelodysplastic syndromes
  • Chronic myelomonocytic leukemia
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Approved in Canada as Vidaza for:
  • Myelodysplastic syndromes
  • Acute myeloid leukemia
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Approved in Japan as Vidaza for:
  • Myelodysplastic syndromes
  • Acute myeloid leukemia

Find a Clinic Near You

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials
3,107
Recruited
1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

Published Research Related to This Trial

In a phase 1b study involving 44 patients with relapsed/refractory higher-risk myelodysplastic syndromes (MDS), the combination of venetoclax and azacitidine demonstrated significant activity, with a median overall survival of 12.6 months after prior treatment failure with hypomethylating agents.
The treatment resulted in hematological improvements, including complete remission in 7% of patients and transfusion independence in 36%, indicating that venetoclax plus azacitidine can provide meaningful clinical benefits for patients with limited options.
A phase 1b study of venetoclax and azacitidine combination in patients with relapsed or refractory myelodysplastic syndromes.Zeidan, AM., Borate, U., Pollyea, DA., et al.[2023]
In a study of 13 patients with acute leukemia treated with venetoclax and azacitidine, 46% developed COVID-19, highlighting a significant risk associated with this treatment during the pandemic.
The study found that 33% of those who contracted COVID-19 died from the virus, indicating that COVID-19 can lead to severe outcomes in patients receiving AZA-VEN therapy.
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.Drozd-SokoΕ‚owska, J., MΔ…dry, K., Barankiewicz, J., et al.[2023]
In a phase 1/2 study involving six Japanese patients aged 60 and older with acute myeloid leukaemia, the combination of venetoclax and azacitidine demonstrated a high response rate, with 83% of patients achieving a response, including three complete remissions.
The treatment was generally well tolerated, with a median overall survival of 15.7 months, although some patients experienced serious adverse events, including grade 3 fungal pneumonia, which required treatment adjustments.
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]

Citations

A phase 1b study of venetoclax and azacitidine combination in patients with relapsed or refractory myelodysplastic syndromes. [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]
Venetoclax in combination with azacitidine in Japanese patients with acute myeloid leukaemia: phase 1 trial findings. [2021]
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 induces deep hematologic remissions in t(11;14) relapsed/refractory AL amyloidosis. [2021]
Irinotecan in lymphoma, leukemia, and breast, pancreatic, ovarian, and small-cell lung cancers. [2018]
Pharmacokinetic mechanisms for reduced toxicity of irinotecan by coadministered thalidomide. [2019]
Clinical pharmacokinetics of irinotecan. [2018]
Recurrent cervical cancer in a patient who was compound heterozygous for UGT1A1*6 and UGT1A1*28 presenting with serious adverse events during irinotecan hydrochloride/nedaplatin therapy. [2018]
11.United Statespubmed.ncbi.nlm.nih.gov
TP53 or Not TP53: That Is the Question. [2023]
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