Study of Venetoclax With the mIDH1 Inhibitor Ivosidenib (AG120) in IDH1-Mutated Hematologic Malignancies
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|ClinicalTrials.gov Identifier: NCT03471260|
Recruitment Status : Recruiting
First Posted : March 20, 2018
Last Update Posted : November 5, 2018
There are 2 parts to this clinical research study: Part 1 (dose escalation) and Part 2 (dose expansion).
The goal of Part 1 of this clinical research study is to find the highest tolerable dose of the combination of ivosidenib (AG-120) and venetoclax that can be given to patients with relapsed (has come back) or refractory (has not responded to treatment) acute myeloid leukemia (AML) with an IDH1 mutation (a type of genetic change).
The goal of Part 2 is to learn if the highest tolerable dose of ivosidenib and venetoclax found in Part 1 can help to control the disease.
The safety of this drug combination will be studied in both parts.
This is an investigational study. Ivosidenib is not FDA approved or commercially available. Venetoclax is FDA approved and commercially available for the treatment of a certain type of chronic lymphocytic leukemia (CLL). It is considered investigational to use ivosidenib in combination with venetoclax to treat AML.
The study doctor can explain how the study drugs are designed to work.
Up to 48 patients will be enrolled on this study. All will take part at MD Anderson.
|Condition or disease||Intervention/treatment||Phase|
|Other Diseases of Blood and Blood-forming Organs Advanced Hematologic Malignancies Acute Myeloid Leukemia||Drug: Ivosidenib Drug: Venetoclax||Phase 1 Phase 2|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||48 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase Ib/II Investigator Sponsored Study of the IDH1-Mutant Inhibitor Ivosidenib (AG120) With the BCL2 Inhibitor Venetoclax in IDH1-Mutated Hematologic Malignancies|
|Actual Study Start Date :||March 19, 2018|
|Estimated Primary Completion Date :||September 2019|
|Estimated Study Completion Date :||September 2019|
Experimental: Ivosidenib + Venetoclax
Participants take Venetoclax by mouth 1 time each day on Days 1-14 of each 28 day cycle.
Participants take Ivosidenib by mouth once each day starting with Day 15 of Cycle 1.
Dose Escalation and Dose Expansion Phase: Ivosidenib 500 mg by mouth once each day starting with Day 15 of Cycle 1.
Other Name: AG120
Dose Escalation Phase Starting Dose: 400 mg by mouth one time each day on Days 1-14 of each 28 day cycle.
Dose Expansion Phase Starting Dose: Maximum tolerated dose from Dose Escalation Phase.
- Incidence and Severity of Adverse Events using Common Toxicity Criteria v 4.0 [ Time Frame: Start of drug combination up to 30 days after drug combination stopped ]
- Dose-Limiting Toxicity (DLT) [ Time Frame: 56 days ]Dose-limiting toxicity (DLT) defined as any grade 3 or 4, clinically significant non-hematologic adverse event or abnormal laboratory value occurring during the first two cycles on study that cannot be attributed by the investigator to a clearly identifiable cause such as disease progression, underlying illness, concurrent illness, or concomitant medication.
- Overall Response Rate (ORR) Defined by CR + CRi + PR + MLFS, CR Rate, CR/CRi Rate [ Time Frame: 3 years ]ORR assessed based on revised IWG response criteria for AML (Cheson et al, JCO 2003).
- Evaluate Molecular and Cellular Biomarkers That May be Predictive of Antitumor Activity and/or Resistance to Treatment by Assessment of the Depth of Response and Monitoring of Disease Recurrence by Assessment of MRD in the Bone Marrow [ Time Frame: Baseline up to 30 days after study drug combination stopped ]
Blood drawn at various time points.
The effects of the combination compared not only to historical outcomes in matched groups of patients, but also at the molecular and cellular level by correlating with karyotype and molecular mutation profile. The NGS gene panel performed on the screening BM aspirate and the progression/relapse BM aspirate.
- Duration of Response (DOR) [ Time Frame: 3 years ]Duration of response defined as the number of days from the date of initial response to the date of first documented disease progression/relapse or death, whichever occurs first.
- Event Free Survival (EFS) [ Time Frame: Start of study treatment up to 3 years ]Event-free survival defined as the number of days from the date of treatment initiation to the date of documented treatment failure, relapse, or death from any cause, whichever occurs first.
- Overall Survival (OS) [ Time Frame: Start of study treatment up to 3 years ]OS assessed based on revised IWG response criteria for AML (Cheson et al, JCO 2003)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03471260
|Contact: Courtney DiNardo, MDemail@example.com|
|United States, Texas|
|University of Texas MD Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Courtney DiNardo, MD||M.D. Anderson Cancer Center|