Study on Azacitidine, Venetoclax, and Gilteritinib for Treating Patients with Recurrent or Hard-to-Treat FLT3-Mutated Blood Cancers

Sponsor: M.D. Anderson Cancer Center

Sponsor score: 0
Inactive

ClinicalTrials ID:NCT04140487

Provider View

This clinical trial is testing a combination of three drugs—azacitidine, venetoclax, and gilteritinib—to see if they can effectively treat patients with certain blood cancers that have a specific FLT3 mutation and have either returned after treatment or not responded to previous treatments.

Patient Parameters

Program Overview

This study is exploring the use of three drugs—azacitidine, venetoclax, and gilteritinib—to treat patients with specific blood cancers that have a mutation called FLT3. These cancers include acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML), and high-risk myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN). The trial aims to find the best dose of gilteritinib and to see how well this combination works in shrinking or controlling the cancer. Azacitidine helps stop cancer cells from growing, venetoclax blocks a protein that cancer cells need to survive, and gilteritinib blocks enzymes that help cancer cells grow. The study will compare the effectiveness of using all three drugs together versus just azacitidine and venetoclax.

Description

The main goals of this study are to find the safest and most effective dose of the drug combination and to see how well it works in treating patients with FLT3-mutated blood cancers. The study is divided into two phases: Phase I focuses on finding the best dose, and Phase II looks at how well the treatment works in achieving remission, where cancer symptoms are reduced or disappear.

Secondary goals include evaluating other measures of effectiveness, such as how long patients stay in remission and overall survival rates. The study will also look at how many patients can proceed to stem cell transplantation and assess the safety of the treatment.

The study will explore how genetic changes in the cancer affect treatment response and survival, and how the cancer evolves over time.

Participants will receive azacitidine either as an injection or through an IV for the first 7 days of each 28-day cycle. Venetoclax will be taken orally every day for the first 28 days of the first cycle and for the first 21 days of the following cycles. Gilteritinib will be taken orally every day for 28-day cycles. Treatment will continue for up to 24 cycles unless the cancer progresses or side effects become unacceptable. After treatment, patients will have follow-up visits at 30 days and then every 6 months.

Eligibility Criteria

Inclusion Criteria

  • Adults aged 18 or older with specific blood cancers that have a FLT3 mutation.
  • For Phase I: Patients with relapsed or refractory FLT3-mutated AML, CMML, or high-risk MDS/MPN.
  • For Phase II:
    • Cohort A: Newly diagnosed FLT3-mutated AML.
    • Cohort B: Relapsed or refractory FLT3-mutated AML, CMML, or high-risk MDS/MPN.
  • Must have either FLT3-ITD or FLT3 D835 mutations.
  • Performance status of 3 or lower on the ECOG scale, indicating varying levels of activity.
  • Acceptable liver and kidney function as indicated by specific blood tests.
  • Ability to swallow pills.
  • Must provide signed informed consent.

Exclusion Criteria

  • For Phase I: No restrictions on previous treatments.
  • For Phase II Cohort A: No prior therapy for AML, except for certain allowed treatments.
  • For Phase II Cohort B: No restrictions on previous treatments.
  • Patients eligible for intensive chemotherapy (Phase II Cohort A only).
  • Certain heart conditions, such as long QT syndrome, unless corrected.
  • Active serious infections not controlled by antibiotics.
  • Severe heart failure or active central nervous system leukemia.
  • Positive for HIV or active hepatitis B or C infections, unless controlled.
  • Recent use of certain medications that affect drug metabolism.
  • Recent treatment with investigational or chemotherapy agents, unless fully recovered.
  • Pregnant or breastfeeding women, and those not willing to use contraception during and after the study.
  • Men must also use effective birth control during and after the study.

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