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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-004095-22 | EudraCT Number |
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To determine the maximum tolerated and / or recommended Phase II dose of oral mutant IDH1 (mIDH1) inhibitor BAY1436032 and to characterize its safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary clinical efficacy in patients with mIDH1-R132X advanced acute myeloid leukemia (AML)
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BAY1436032 | Experimental | Dose escalation: Various doses of study drug will be tested on a small number of patients/dose with the goal of identifying the most appropriate dose(s) for further evaluation in dose expansion. The MTD of the study drug may or may not be identified. It is anticipated that 3-4 patients will be treated at each dose of study drug to be tested and that 15-20 total patients will be treated in this part of the trial. Dose expansion: Up to 2 different doses of study drug will be tested on up to 30 patients/dose with the goal of identifying the most appropriate RP2D for further clinical development. The doses to be evaluated in this part of the trial will be selected based on information obtained during dose escalation. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BAY1436032 | Drug | BAY1436032 administered continuously as a single agent dosed twice a day orally on Days 1 to 28 of a 28-day cycle. Patients may continue treatment with BAY1436032 until disease progression, development of other unacceptable toxicity or Investigator discretion. |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum tolerated dose (MTD) or RP2D of BAY1436032 | If the MTD is not reached during dose escalation, the primary variable will be the recommended phase 2 dose (RP2D) of BAY1436032 | Within first 4 weeks of first dose |
| Number of participants with Adverse Events as a Measure of | As a measure of safety and tolerability | Up to 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Objective efficacy response | Response assessment for AML in this study will be based on the modified Cheson criteria. The following categories are used to capture the investigator's AML response evaluation:
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Roswell Park Comprehensive Cancer Center | Buffalo | New York | 14263-0001 | United States | ||
| Mount Sinai Medical Center |
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|
| Up to 12 weeks |
| Duration of response | Efficacy data | Up to 12 weeks |
| Event-free survival (EFS) | EFS defined as time from start of treatment to treatment failure, relapse, or death due to any cause. | Up to 12 weeks |
| Change of 2 hydroxyglutarate (2-HG) level obtained at baseline and post-baseline | Assess pharmacodynamic (PD) effects and evidence of clinical efficacy associated with BAY 1436032 administration in patients. Change from baseline and percent change from baseline will be calculated. | Up to 12 weeks |
| Cmax (maximum observed drug concentration in plasma after a single dose) | As a secondary objective of this study evaluate the pharmacokinetics (PK) of BAY 1436032 in patients. PK parameters normalized for dose and / or dose and body weight will be calculated. | Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hour post-dose (each cycle is 28 days) |
| AUC(0-8) (AUC from time 0 to 8 h after a single dose) | As a secondary objective of this study evaluate the pharmacokinetics (PK) of BAY 1436032 in patients. PK parameters normalized for dose and / or dose and body weight will be calculated. | Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hour post-dose (each cycle is 28 days) |
| AUC(0-12) (AUC from time 0 to 12 h after a single dose) | if feasible | Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hour post-dose (each cycle is 28 days) |
| Cmax,md (Cmax after multiple doses) | As a secondary objective of this study evaluate the pharmacokinetics (PK) of BAY 1436032 in patients. PK parameters normalized for dose and / or dose and body weight will be calculated. | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 12 hour post-dose on Day 15; (each cycle is 28 days) |
| AUC(0-8)md (AUC from time 0 to 8 h after multiple doses) | As a secondary objective of this study evaluate the pharmacokinetics (PK) of BAY 1436032 in patients. PK parameters normalized for dose and / or dose and body weight will be calculated. | Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hour post-dose on Day 15; (each cycle is 28 days) |
| AUC(0-12)md (AUC from time 0 to 12 h after multiple doses) | if feasible | Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hour post-dose on Day 15; (each cycle is 28 days) |
| New York |
| New York |
| 10029 |
| United States |
| Montefiore Medical Center | The Bronx | New York | 10467-2490 | United States |
| Wake Forest Baptist Health | Winston-Salem | North Carolina | 27157 | United States |
| Ohio State University | Columbus | Ohio | 43210 | United States |
| University of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
| Thomas Jefferson University | Philadelphia | Pennsylvania | 19107 | United States |
| University of Texas MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
| Universitätsklinikum Heidelberg | Heidelberg | Baden-Wurttemberg | 69120 | Germany |
| Medizinische Hochschule Hannover (MHH) | Hanover | Lower Saxony | 30625 | Germany |
| Universitätsklinikum Leipzig AöR | Leipzig | Saxony | Germany |
| Universitätsklinikum Charite zu Berlin | Berlin | 12200 | Germany |
| Universitätsklinikum Hamburg Eppendorf (UKE) | Hamburg | 20246 | Germany |
| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| C000622445 | BAY 1436032 |
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