RECRUITING

Ivosidenib and Venetoclax With or Without Azacitidine in Treating Patients With IDH1 Mutated Hematologic Malignancies

Conditions

Acute Myeloid Leukemia Hematopoietic and Lymphoid System Neoplasm Myelodysplastic Syndrome Myeloproliferative Neoplasm Recurrent Acute Myeloid Leukemia Refractory Acute Myeloid Leukemia

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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

This phase Ib/II trial studies the side effects and best dose of venetoclax and how well it works when given together with ivosidenib with or without azacitidine, in treating patients with IDH1-mutated hematologic malignancies. Venetoclax and ivosidenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as 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. Giving ivosidenib and venetoclax with azacitidine may work better in treating patients with hematologic malignancies compared to ivosidenib and venetoclax alone.

Official Title

Phase Ib/II Investigator Initiated Study of the IDH1-Mutant Inhibitor Ivosidenib (AG120) With the BCL2 Inhibitor Venetoclax +/- Azacitidine in IDH1-Mutated Hematologic Malignancies

Quick Facts

Study Start:2018-03-19

Study Completion:2025-09-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT03471260

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. ECOG performance status of \< 2. 3. IDH1-R132 mutated disease status as assessed by local laboratory. 2HG-producing IDH1 variants outside of R132 (i.e. R100) may be eligible after discussion with the PI. 4. Relapsed/refractory AML, or treatment-naïve patients with AML who are not eligible for standard induction chemotherapy. Patients with high-risk MDS, MDS/MPN or MPN (defined as \> 10% bone marrow blasts, or intermediate or high risk by IPSS, R-IPSS or D-IPSS) that have failed standard therapy may also be eligible after discussion with the PI. 5. Adequate hepatic function (direct bilirubin \< 2 x ULN, ALT and/or AST \< 3x ULN) unless deemed to be related to underlying leukemia. 6. Adequate renal function including creatinine clearance \> 30 ml/min based on the Cockcroft-Gault equation. 7. Willing and able to provide informed consent 8. In the absence of rapidly proliferative disease, the interval from prior treatment to time of initiation will be at least 7 days for cytotoxic or non-cytotoxic (immunotherapy) agents. 9. Male subjects must agree to refrain from unprotected sex and sperm donation from initial study drug administration until 90 days after the last dose of study drug.	1. Patients with known allergy or hypersensitivity to ivosidenib or venetoclax. 2. Patients who have previously received either ivosidenib or venetoclax. 3. Patients with any concurrent uncontrolled clinically significant medical condition including infection, laboratory abnormality, or psychiatric illness, which could place the patient at unacceptable risk of study treatment. 4. The use of other chemotherapeutic agents or anti-leukemic agents is not permitted during study with the following exceptions (1) intrathecal chemotherapy for prophylactic use or for controlled CNS leukemia. (2) use of hydroxyurea and/or one dose of cytarabine (up to 2 g/m2) for patients with rapidly proliferative disease is allowed before the start of study therapy and for the first four weeks on therapy. 5. Patients receiving concomitant strong CYP3A inducers (avasimibe, carbamazepine, phenytoin, rifampin, rifabutin, St. John's wort) within 3 days of start of study therapy. 6. Patients 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). 7. Patients with any severe gastrointestinal or metabolic condition which could interfere with the absorption of oral study medications. 8. Patients with a concurrent active malignancy under treatment. 9. QTc interval using Fridericia's formula (QTcF) \> 450 msec. Bundle branch block and prolonged QTc interval are permitted after discussion with the PI. 10. Known active hepatitis B (HBV) or Hepatitis C (HCV) infection or known HIV infection. 11. Subject has a white blood cell count \> 25 x 10⁹/L. (Note: Hydroxyurea is permitted to meet this criterion.) 12. 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 a. Appropriate highly effective method(s) of contraception include oral or injectable hormonal birth control, IUD, and double barrier methods (for example a condom in combination with a spermicide).

Inclusion Criteria

Exclusion Criteria

1. Age \> 18 years.
2. ECOG performance status of \< 2.
3. IDH1-R132 mutated disease status as assessed by local laboratory. 2HG-producing IDH1 variants outside of R132 (i.e. R100) may be eligible after discussion with the PI.
4. Relapsed/refractory AML, or treatment-naïve patients with AML who are not eligible for standard induction chemotherapy. Patients with high-risk MDS, MDS/MPN or MPN (defined as \> 10% bone marrow blasts, or intermediate or high risk by IPSS, R-IPSS or D-IPSS) that have failed standard therapy may also be eligible after discussion with the PI.
5. Adequate hepatic function (direct bilirubin \< 2 x ULN, ALT and/or AST \< 3x ULN) unless deemed to be related to underlying leukemia.
6. Adequate renal function including creatinine clearance \> 30 ml/min based on the Cockcroft-Gault equation.
7. Willing and able to provide informed consent
8. In the absence of rapidly proliferative disease, the interval from prior treatment to time of initiation will be at least 7 days for cytotoxic or non-cytotoxic (immunotherapy) agents.
9. Male subjects must agree to refrain from unprotected sex and sperm donation from initial study drug administration until 90 days after the last dose of study drug.

1. Patients with known allergy or hypersensitivity to ivosidenib or venetoclax.
2. Patients who have previously received either ivosidenib or venetoclax.
3. Patients with any concurrent uncontrolled clinically significant medical condition including infection, laboratory abnormality, or psychiatric illness, which could place the patient at unacceptable risk of study treatment.
4. The use of other chemotherapeutic agents or anti-leukemic agents is not permitted during study with the following exceptions (1) intrathecal chemotherapy for prophylactic use or for controlled CNS leukemia. (2) use of hydroxyurea and/or one dose of cytarabine (up to 2 g/m2) for patients with rapidly proliferative disease is allowed before the start of study therapy and for the first four weeks on therapy.
5. Patients receiving concomitant strong CYP3A inducers (avasimibe, carbamazepine, phenytoin, rifampin, rifabutin, St. John's wort) within 3 days of start of study therapy.
6. Patients 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).
7. Patients with any severe gastrointestinal or metabolic condition which could interfere with the absorption of oral study medications.
8. Patients with a concurrent active malignancy under treatment.
9. QTc interval using Fridericia's formula (QTcF) \> 450 msec. Bundle branch block and prolonged QTc interval are permitted after discussion with the PI.
10. Known active hepatitis B (HBV) or Hepatitis C (HCV) infection or known HIV infection.
11. Subject has a white blood cell count \> 25 x 10⁹/L. (Note: Hydroxyurea is permitted to meet this criterion.)
12. 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 a. Appropriate highly effective method(s) of contraception include oral or injectable hormonal birth control, IUD, and double barrier methods (for example a condom in combination with a spermicide).

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)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215

United States

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195

United States

Oregon Health and Science University

Portland, Oregon, 97239

United States

M D 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 Date2018-03-19

Study Completion Date2025-09-30

Study Record Updates

Study Start Date2018-03-19

Study Completion Date2025-09-30

Terms related to this study

Additional Relevant MeSH Terms

Acute Myeloid Leukemia
Hematopoietic and Lymphoid System Neoplasm
Myelodysplastic Syndrome
Myeloproliferative Neoplasm
Recurrent Acute Myeloid Leukemia
Refractory Acute Myeloid Leukemia