Comparing treatment sequences for older patients with IDH mutated acute myeloid leukemia

Randomized, Sequential, Open-Label Study to Evaluate the Efficacy of IDH Targeted/Non- Targeted Versus Non-targeted/IDH-targeted Approaches in the Treatment of Newly Diagnosed IDH Mutated AML Patients Not Candidates for Intensive Induction Therapy (I- DATA Study)

This study is testing which order of treatments works better for older patients with a specific type of leukemia that can't handle intensive therapy, by comparing an IDH inhibitor with venetoclax, both combined with azacitidine.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 125 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Ohio State University Comprehensive Cancer Center (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 2 sites (Columbus, Ohio and 1 other locations)
• Trial ID: NCT05401097 on ClinicalTrials.gov

What this trial studies

This phase II study evaluates the effectiveness of two different treatment sequences for older patients with newly diagnosed acute myeloid leukemia (AML) who have mutations in the IDH1 or IDH2 genes and are not candidates for intensive induction therapy. Patients will be randomized to receive either an IDH inhibitor followed by venetoclax or vice versa, both in combination with azacitidine. The study aims to determine which treatment order results in better overall treatment outcomes, including survival rates and response durations, while also assessing the toxicity profiles of each approach.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with newly diagnosed IDH1 or IDH2 mutated AML who are not suitable for intensive chemotherapy.

Not a fit: Patients with non-IDH mutated AML or those who are candidates for intensive induction therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a more effective treatment strategy for older patients with IDH mutated AML, potentially improving their survival and quality of life.

How similar studies have performed: While there have been studies on IDH inhibitors and venetoclax individually, this specific comparison of treatment sequences is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

* Patients with newly diagnosed IDH1 or IDH2 mutated AML
* Not a candidate for or refuses intensive induction therapy
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
* Creatinine clearance \> 40 ml/min
* Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) \< 5 x upper limit of normal
* Total bilirubin \< 1.5 x upper limit of normal (except for patients with Gilbert's disease)
* At the time of Venetoclax initiation, white blood cells (WBC) needs to be \< 25 × 103 microliter: Hydroxyurea can be used to achieve that level.
* For female patients of childbearing potential, willingness to abstain from heterosexual intercourse or use a protocol-recommended method of contraception from the screening visit throughout the study treatment period and for 30 days following the last dose of either study drug. A serum pregnancy test will be done at screening. A serum or urine pregnancy test will be done on Day 1 of each cycle for women of childbearing potential. If the urine pregnancy test is positive, a serum pregnancy test must be performed per institutional standards.

The following methods are acceptable methods of contraception for the purpose of this study:

* Highly Effective Contraception Methods that can achieve a failure rate of less than 1% per year when used consistently and correctly are considered as highly effective birth control methods (Clinical Trials Facilitation Group 2014):

  * Combined (estrogen and progestin containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal).
  * Progestin-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable).
  * Intrauterine device.
  * Intrauterine hormone-releasing system.
  * Bilateral tubal occlusion.
  * Vasectomized partner, provided that partner is the sole sexual partner of the female study participant and that the vasectomized partner has received medical assessment of the surgical success.
  * Sexual abstinence- only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the patient.
* Acceptable Birth Control Methods that are not Highly Effective Contraception Acceptable birth control methods that result in a failure rate of more than 1% per year:

  * Progestin-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of action.
  * Male or female condom with or without spermicide.
  * Cap, diaphragm, or sponge with spermicide. A combination of male condom with either cap, diaphragm, or sponge with spermicide (double barrier methods) are also acceptable, but not highly effective, birth control methods.
* The following methods are NOT acceptable methods of contraception for the purpose of this study:

  * Periodic abstinence (calendar, symptothermal, postovulation methods).
  * Withdrawal (coitus interruptus).
  * Spermicides only.
  * Lactational amenorrhea method.
  * Combination of male and female condom
* For male patients of childbearing potential having intercourse with females of childbearing potential, the willingness to abstain from heterosexual intercourse or use a protocol recommended method of contraception from the start of study treatment throughout the study treatment period and for 90 days following the last dose of either study drug. Males must also refrain from sperm donation from the start of study treatment throughout the study treatment period and for 90 days following the last dose of either dose of study drug

  * Willingness to comply with scheduled visits, drug administration plan, imaging studies, laboratory tests, other study procedures and study restrictions

Exclusion Criteria:

* Patients with acute promyelocytic leukemia
* Known active central nervous system involvement of leukemia
* History of active non-myeloid malignancy except for the following: adequately treated local basal cell carcinoma or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer without known metastatic disease. patients receiving tamoxifen/Aromatase Inhibitors for non-metastatic breast cancer, or any other cancer that has been in complete remission without treatment for \>= 5 years prior to enrollment
* Evidence of ongoing uncontrolled systemic bacterial, fungal or viral infection at the time of start of study treatment
* Uncontrolled infection with hepatitis C, hepatitis B, or human immunodeficiency virus (HIV)
* Pregnancy or breast feeding
* Concurrent participation in an investigational drug trial with therapeutic intent defined as prior study therapy within 14 days prior to study treatment
* Inability to tolerate oral medications including symptomatic disease significantly affecting gastrointestinal function such as inflammatory bowel disease or resection of stomach or small bowel

Where this trial is running

Columbus, Ohio and 1 other locations

• Ohio State University Comprehensive Cancer Center — Columbus, Ohio, United States (Recruiting)
• UT Southwestern Medical Center at Dallas — Dallas, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Alice S Mims, MD — Ohio State University Comprehensive Cancer Center
• Study coordinator: The Ohio State University Comprehensive Cancer Center

Conditions Acute Myeloid Leukemia