RECRUITING

Phase 1b/2 Study of Decitabine and Venetoclax in Combination With the Targeted Mutant IDH1 Inhibitor Olutasidenib

Conditions

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

To find a recommended combination dose of decitabine and venetoclax that can be given in combination with olutasidenib to participants with AML.

Official Title

Phase 1b/2 Study of Decitabine and Venetoclax in Combination With the Targeted Mutant IDH1 Inhibitor Olutasidenib

Quick Facts

Study Start:2024-08-29

Study Completion:2029-06-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06445959

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Age \> 18 years 2. Participants must have a documented IDH1 gene mutation 3. Participants with a diagnosis of relapsed or refractory AML (including biphenotypic or bilineage leukemia including a myeloid component or isolated extramedullary AML), high-risk MDS by IPSS-R or IPSS-M; OR 4. Participants with newly diagnosed AML not eligible or appropriate for intensive chemotherapy are also eligible. (Phase 2 portion only) 5. To be considered not eligible for intensive chemotherapy, participants must be defined by the following: Age 75 years or older, or Age 18 to 74 years with at least one of the following comorbidities: 1. Severe cardiac disorder (eg, congestive heart failure requiring treatment, ejection fraction ≤50%, or chronic stable angina). 2. Severe pulmonary disorder (eg, DLCO ≤65% or forced expiratory volume in 1 second \[FEV1\] ≤65%). 3. Creatinine clearance ≥30 mL/min to \<45 mL/min. 4. Moderate hepatic impairment with total bilirubin \>1.5 to .3.0 x upper limit of normal (ULN) 5. ECOG performance status of 2 or 3 6. Any other comorbidity that per the investigator renders a patient inappropriate for intensive chemotherapy 6. Eastern Cooperative Oncology Group (ECOG) Performance Status \</=2 (unless age 18 to 74 years of age with newly diagnosed AML not eligible for intensive chemotherapy as per 5e above) 7. Adequate renal function including creatinine \< 1.5, unless related to the disease or unless age 18 to 74 years of age with newly diagnosed AML not eligible for intensive chemotherapy as per 5c above. 8. Adequate hepatic function (direct bilirubin \< 2x upper limit of normal (ULN) unless increase is due to Gilbert fs disease or leukemic involvement, and AST and/or ALT \< 3x ULN unless considered due to leukemic involvement, in which case direct bilirubin or AST and/or ALT \< 5x ULN will be considered eligible, or unless age 18 to 74 years of age with newly diagnosed AML not eligible for intensive chemotherapy as per 5d above) 9. In the absence of rapidly proliferative disease, the interval from prior treatment to time of initiation will be at least 14 days for cytotoxic or non-cytotoxic (immunotherapy agent(s), or an interval of 5 half-lives of the prior therapy. Oral hydroxyurea and/or cytarabine (up to 2 g/m2) for patients with rapidly proliferative disease is allowed before the start of study therapy, as needed, for clinical benefit and after discussion with the PI. Concurrent intrathecal therapy for central nervous system (CNS) prophylaxis or continuation of therapy for controlled CNS disease is permitted. 10. Male participants who are sexually active with a women of childbearing potential (WOCBP) and who have not had vasectomies must be willing to use a barrier method of contraception and refrain from sperm donation from initial study drug until 90 days after last dose of study drug. 11. Willing and able to provide informed consent.	1. Participants with t(15;17) karyotypic abnormality or acute promyelocytic leukemia (French-American-British \[FAB\] class M3-AML). 2. Participants with any concurrent uncontrolled clinically significant medical condition including life-threatening severe infection, or psychiatric illness, which could place the participants at unacceptable risk of study treatment. 3. Participants with active, uncontrolled leukemia involvement of the CNS 4. Participants with active graft-versus-host-disease (GVHD) status post stem cell transplant (patients without active GVHD on chronic suppressive immunosuppression and/or phototherapy for chronic skin GVHD are permitted after discussion with the PI). 5. Participants with any severe gastrointestinal or metabolic condition which could interfere with the absorption of oral study medications. 6. Known active hepatitis B (HBV) or Hepatitis C (HCV) infection or known HIV infection. 7. Participant has a white blood cell count \> 25 x 10\^9/L. (Note: Hydroxyurea and cytarabine is permitted to meet this criterion.) 8. Nursing women, women of childbearing potential (WOCBP) with positive urine pregnancy test, or women of childbearing potential who are not willing to maintain adequate contraception.

Inclusion Criteria

Exclusion Criteria

1. Age \> 18 years
2. Participants must have a documented IDH1 gene mutation
3. Participants with a diagnosis of relapsed or refractory AML (including biphenotypic or bilineage leukemia including a myeloid component or isolated extramedullary AML), high-risk MDS by IPSS-R or IPSS-M; OR
4. Participants with newly diagnosed AML not eligible or appropriate for intensive chemotherapy are also eligible. (Phase 2 portion only)
5. To be considered not eligible for intensive chemotherapy, participants must be defined by the following: Age 75 years or older, or Age 18 to 74 years with at least one of the following comorbidities:
1. Severe cardiac disorder (eg, congestive heart failure requiring treatment, ejection fraction ≤50%, or chronic stable angina).
2. Severe pulmonary disorder (eg, DLCO ≤65% or forced expiratory volume in 1 second \[FEV1\] ≤65%).
3. Creatinine clearance ≥30 mL/min to \<45 mL/min.
4. Moderate hepatic impairment with total bilirubin \>1.5 to .3.0 x upper limit of normal (ULN)
5. ECOG performance status of 2 or 3
6. Any other comorbidity that per the investigator renders a patient inappropriate for intensive chemotherapy
6. Eastern Cooperative Oncology Group (ECOG) Performance Status \</=2 (unless age 18 to 74 years of age with newly diagnosed AML not eligible for intensive chemotherapy as per 5e above)
7. Adequate renal function including creatinine \< 1.5, unless related to the disease or unless age 18 to 74 years of age with newly diagnosed AML not eligible for intensive chemotherapy as per 5c above.
8. Adequate hepatic function (direct bilirubin \< 2x upper limit of normal (ULN) unless increase is due to Gilbert fs disease or leukemic involvement, and AST and/or ALT \< 3x ULN unless considered due to leukemic involvement, in which case direct bilirubin or AST and/or ALT \< 5x ULN will be considered eligible, or unless age 18 to 74 years of age with newly diagnosed AML not eligible for intensive chemotherapy as per 5d above)
9. In the absence of rapidly proliferative disease, the interval from prior treatment to time of initiation will be at least 14 days for cytotoxic or non-cytotoxic (immunotherapy agent(s), or an interval of 5 half-lives of the prior therapy. Oral hydroxyurea and/or cytarabine (up to 2 g/m2) for patients with rapidly proliferative disease is allowed before the start of study therapy, as needed, for clinical benefit and after discussion with the PI. Concurrent intrathecal therapy for central nervous system (CNS) prophylaxis or continuation of therapy for controlled CNS disease is permitted.
10. Male participants who are sexually active with a women of childbearing potential (WOCBP) and who have not had vasectomies must be willing to use a barrier method of contraception and refrain from sperm donation from initial study drug until 90 days after last dose of study drug.
11. Willing and able to provide informed consent.

1. Participants with t(15;17) karyotypic abnormality or acute promyelocytic leukemia (French-American-British \[FAB\] class M3-AML).
2. Participants with any concurrent uncontrolled clinically significant medical condition including life-threatening severe infection, or psychiatric illness, which could place the participants at unacceptable risk of study treatment.
3. Participants with active, uncontrolled leukemia involvement of the CNS
4. Participants with active graft-versus-host-disease (GVHD) status post stem cell transplant (patients without active GVHD on chronic suppressive immunosuppression and/or phototherapy for chronic skin GVHD are permitted after discussion with the PI).
5. Participants with any severe gastrointestinal or metabolic condition which could interfere with the absorption of oral study medications.
6. Known active hepatitis B (HBV) or Hepatitis C (HCV) infection or known HIV infection.
7. Participant has a white blood cell count \> 25 x 10\^9/L. (Note: Hydroxyurea and cytarabine is permitted to meet this criterion.)
8. Nursing women, women of childbearing potential (WOCBP) with positive urine pregnancy test, or women of childbearing potential who are not willing to maintain adequate contraception.

Contacts and Locations

Study Contact

Courtney DiNardo, MD

CONTACT

(713) 794-1141

cdinardo@mdanderson.org

Principal Investigator

Courtney DiNardo, MD

PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Study Locations (Sites)

MD Anderson Cancer Center

Houston, Texas, 77030

United States

Collaborators and Investigators

Sponsor: M.D. Anderson Cancer Center

Courtney DiNardo, MD, PRINCIPAL_INVESTIGATOR, M.D. Anderson Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-08-29

Study Completion Date2029-06-30

Study Record Updates

Study Start Date2024-08-29

Study Completion Date2029-06-30

Terms related to this study

Additional Relevant MeSH Terms

Mutant IDH1 Inhibitor Olutasidenib