Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02670044
Other study ID # GH29914
Secondary ID 2015-003386-28
Status Completed
Phase Phase 1
First received
Last updated
Start date March 9, 2016
Est. completion date December 10, 2020

Study information

Verified date December 2021
Source Hoffmann-La Roche
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The primary objective for this study is to assess the safety and tolerability as well as preliminary efficacy of venetoclax in combination with cobimetinib, and venetoclax in combination with idasanutlin in patients with relapsed or refractory acute myeloid leukemia (R/R) AML who are not eligible for cytotoxic therapy.


Recruitment information / eligibility

Status Completed
Enrollment 88
Est. completion date December 10, 2020
Est. primary completion date December 10, 2020
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Histological confirmation of relapsed or refractory AML after prior anti-leukemic therapy by WHO classification - Ineligible for cytotoxic therapy defined by the following: a. Age (>/=) 75 years or b. age 18- 74 years with at least one of the following comorbidities: i. Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 or 3 ii. Cardiac history of congestive heart failure requiring treatment or ejection fraction (</=) 50% or chronic stable angina iii. Diffusing capacity of the lungs for carbon monoxide (</=) 65% or forced expiratory volume in the first second of expiration (</=) 65% iv. Creatinine clearance (>/=) 30 mL/min to< 45 mL/min v. any other comorbidity that the physician judges to be incompatible with intensive chemotherapy must be reviewed and approved by the Medical Monitor before screening and study enrollment. - Life expectancy of at least 12 weeks - Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 - Adequate liver and renal function Exclusion Criteria: - Patients with acute promyelocytic leukemia (French-American-British [FAB] class M3 AML) - Known active central nervous system (CNS) involvement with AML at study entry - ECOG Performance Status (>/=) 3 in patients who are (>/=) 75 years old or ECOG Performance Status of 4, regardless of age - Prior exposure to Bcl-2 inhibitors, murine double minute 2 (MDM2) antagonists or prior exposure to experimental treatment targeting Raf, mitogen-activated protein kinase (MEK), or the mitogen-activated protein kinase (MAPK) RAS/RAF/MEK/ERK MAPK pathway - Positive for hepatitis C virus (HCV), hepatitis B surface antigen (HBsAg) and known history of HIV, malignancy, active infection and cardiovascular diseases (CVs) - Received strong cytochrome (CYP) 3A inhibitors, moderate CYP3A inhibitors, strong CYP3A inducers and moderate CYP3A inducers within 7 days prior to initiation of study treatment - History of symptomatic Clostridium difficile infection within 1 month prior to dosing Additional arm specific exclusion criteria: Dose Escalation Arm A (Venetoclax and Cobimetinib): - History or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/central serous chorioretinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular degeneration - Left ventricular ejection fraction (LVEF) below institutional lower limit of normal (LLN) or below 50%, whichever is lower Arm B (Venetoclax and Idasanutlin): - Received the following within 7 days prior to the initiation of study treatment: Strong CYP2C8 inhibitors or CYP2C8 substrates, OATP1B1/3 substrates - Received the following within 14 days prior to the initiation of study treatment: Strong CYP2C8 inducers - History of liver cirrhosis by radiologic, clinical or laboratory data, or biopsy despite normal liver function tests - Received treatment with oral or parenteral anticoagulants/anti-platelet agents within 7 days prior to initiation of study treatment.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Cobimetinib
Cobimetinib will be administered orally as per schedule in Arm description.
Idasanutlin
Idasanutlin will be administered orally as per schedule in Arm description.
Venetoclax
Venetoclax will be administered orally as per schedule in Arm description.

Locations

Country Name City State
Canada University of Alberta Hospital Edmonton Alberta
Canada Jewish General Hospital Montreal Quebec
Canada Princess Margaret Cancer Center Toronto Ontario
France Hopital Avicenne, Paris Bobigny
France Institut Paoli Calmettes Marseille
France CHU de Bordeaux Pessac
Italy University of Bologna Bologna Emilia-Romagna
Italy Presidio san salvatore muraglia Pesaro Emilia-Romagna
Italy Universita di Roma Roma Emilia-Romagna
United States University of Colorado Aurora Colorado
United States Dana Farber Cancer Institute Boston Massachusetts
United States MD Anderson Cancer Center Houston Texas
United States USC Norris Cancer Center Los Angeles California
United States Weill Cornell Medical College New York New York
United States UC Davis; Comprehensive Cancer Center Sacramento California
United States Univ of Calif, San Francisco San Francisco California
United States Wake Forest Baptist Medical Center Winston-Salem North Carolina

Sponsors (1)

Lead Sponsor Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Canada,  France,  Italy, 

Outcome

Type Measure Description Time frame Safety issue
Primary Number of Participants with Dose Limiting Toxicities (DLTs) From Cycle 1 Day 1 to Cycle 2 Day 1 for a minimum of 28 days
Primary Number of Participants with Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) Baseline up until 30 days after the last dose of study drug (up to a maximum of 4 years, 9 months)
Secondary Overall Response Rate (ORR) (Complete Remission (CR) + Complete Remission with Incomplete Blood Recovery (CRi) + Incomplete Platelet Count Recovery (CRp) + Partial Remission/Partial Response [PR]) Up to 2 years
Secondary Complete Remission/complete response (CR) + Complete Remission with Incomplete Blood Recovery (CRi) + Incomplete Platelet Count Recovery (CRp) Up to 2 years
Secondary CR + Complete Remission with Partial Hematologic Recovery (CRh) Rate Up to 2 years
Secondary Duration of Response (DOR) Up to 2 years
Secondary Time to Progression (TTP) Up to 2 years
Secondary Progression-Free Survival (PFS) Up to 2 years
Secondary Event-Free Survival (EFS) Up to 2 years
Secondary Leukemia-Free Survival (LFS) Up to 2 years
Secondary Overall Survival (OS) Up to 2 years
Secondary Pharmacokinetics of Venetoclax Area Under the Concentration-Time Curve from Time Zero to Last Measurable Concentration (AUC0-24hr) Up to 6 months
Secondary Pharmacokinetics of Venetoclax Maximum Observed Concentration (Cmax) Up to 6 months
Secondary Pharmacokinetics of Cobimetinib Area Under the Concentration-Time Curve from Time Zero to Last Measurable Concentration (AUC0-24hr) Up to 6 months
Secondary Pharmacokinetics of Cobimetinib Maximum Observed Concentration (Cmax) Up to 6 months
Secondary Pharmacokinetics of Idasanutlin Area Under the Concentration-Time Curve from Time Zero to Last Measurable Concentration (AUC0-24hr) Up to 6 months
Secondary Pharmacokinetics of Idasanutlin Maximum Observed Concentration (Cmax) Up to 6 months
Secondary Number of Participants Reporting Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire Up to 2 years
Secondary Rate of Transfusion Independence Up to 2 years
Secondary Duration Of Transfusion Independence, Defined As The Number Of Consecutive Days Of Transfusion Independence, Measured From 1 Day After Last Transfusion To Disease Progression Or Subsequent Transfusion Up to 2 years
Secondary Minimal Residual Disease (MRD) In The Bone Marrow To Evaluate The Depth Of Response Up to 2 years
See also
  Status Clinical Trial Phase
Recruiting NCT05319587 - Study of Liposomal Annamycin in Combination With Cytarabine for the Treatment of Subjects With Acute Myeloid Leukemia (AML) Phase 1/Phase 2
Active, not recruiting NCT04090736 - Study to Compare Azacitidine Plus Pevonedistat Versus Azacitidine in Patients With Acute Myeloid Leukemia Not Eligible for Standard Chemotherapy Phase 3
Completed NCT01617226 - Randomised Study of Azacitidine Versus Azacitidine With Vorinostat in Patients With AML or High Risk MDS Phase 2
Terminated NCT00916045 - Pilot Study of Unrelated Cord Blood Transplantation Phase 2
Terminated NCT00957580 - Trial of Pimasertib in Hematological Malignancies Phase 2
Completed NCT00640796 - Pilot Study of Expanded, Donor Natural Killer Cell Infusions for Refractory Non-B Lineage Hematologic Malignancies and Solid Tumors Phase 1
Completed NCT00458250 - Feasibility of Haploidentical Hematopoietic Stem Cell Transplantation Using CAMPATH-1H Phase 1
Active, not recruiting NCT05424380 - A Phase 1, Open Label Study of Intravenous GSK3745417 to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Determine RP2D & Schedule in Participants With Relapsed or Refractory Myeloid Malignancies Including AML and HR MDS Phase 1
Completed NCT01690624 - BI 836858 Dose Escalation in Patients With Refractory or Relapsed Acute Myeloid Leukemia and in Patients in Complete Remission With High Risk to Relapse Phase 1
Recruiting NCT05471700 - Single Arm Study of Azacitidine and Venetoclax for Treatment of Newly Diagnosed Fit Acute Myeloid Leukemia Patients Phase 1/Phase 2
Not yet recruiting NCT05016063 - Dual CD33-CLL1-CAR-T Cells in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia Early Phase 1
Not yet recruiting NCT04450784 - ObServatory Children Acute RElated Therapy Leukemia
Recruiting NCT04265963 - CD123-Targeted CAR-T Cell Therapy for Relapsed/Refractory Acute Myeloid Leukemia Phase 1/Phase 2
Terminated NCT04968860 - Oral Health Condition and Quality of Life in Children With Leukemia
Recruiting NCT03793517 - Decitabine Plus mBU/CY for High Risk Acute Leukemia With MRD Pre-HSCT Phase 2/Phase 3
Terminated NCT02841540 - A Study of H3B-8800 (RVT-2001) in Participants With Lower Risk Myelodysplastic Syndromes Phase 1
Recruiting NCT05453903 - A Study of JNJ-75276617 in Combination With Acute Myeloid Leukemia (AML) Directed Therapies Phase 1
Completed NCT03720366 - A Study of Perpetrator Drug Interactions of Enasidenib in AML Patients Phase 1
Withdrawn NCT04230564 - Acute Myeloid Leukemia Real World Treatment Patterns
Terminated NCT03761069 - Study of PTC299 (Emvododstat) in Relapsed/Refractory Acute Leukemias Phase 1