NCT01685892

Brief Summary

This multi-center, open-label, dose-finding study will evaluate the safety and pharmacokinetics as well as the preliminary efficacy of venetoclax (GDC-0199; ABT-199) administered in combination with obinutuzumab to participants with relapsed/refractory or previously untreated chronic lymphocytic leukemia (CLL). The study is comprised of two stages for each participant population: a dose-finding stage and a safety-expansion stage. The dose-finding stage will explore multiple doses of venetoclax to be used in combination with a fixed dose of obinutuzumab. The dose-finding stage will also explore two schedules for drug administration, Schedule A (venetoclax introduced before obinutuzumab) and Schedule B (venetoclax introduced after obinutuzumab).

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
82

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Nov 2012

Longer than P75 for phase_1

Geographic Reach
2 countries

10 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 12, 2012

Completed
2 days until next milestone

First Posted

Study publicly available on registry

September 14, 2012

Completed
3 months until next milestone

Study Start

First participant enrolled

November 29, 2012

Completed
5.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 21, 2018

Completed
1.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

August 23, 2019

Completed
Last Updated

January 10, 2020

Status Verified

January 1, 2020

Enrollment Period

5.5 years

First QC Date

September 12, 2012

Last Update Submit

January 7, 2020

Conditions

Lymphocytic Leukemia, Chronic

Outcome Measures

Primary Outcomes (2)

  • Percentage of Participants With Dose Limiting Toxicities (DLTs)

    Schedule (Sch) A (Cycle 1 Day 1 to Day 21), Sch B (Cycle 1 Day 22 to Cycle 2 Day 28) (1 Cycle=28 days)

  • Maximum Tolerated Dose (MTD) of Venetoclax in Combination with Obinutuzumab

    Sch A (Cycle 1 Day 1 to Day 21), Sch B (Cycle 1 Day 22 to Cycle 2 Day 28) (1 Cycle=28 days)

Secondary Outcomes (17)

  • Percentage of Participants with Adverse Events

    Baseline up to end of study (up to approximately 5 years and 5 months)

  • Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) to Obinutuzumab

    Baseline up to Cycle 6 (1 Cycle=28 days)

  • Area Under the Concentration-Time Curve (AUC) of Venetoclax

    Baseline up to Cycle 6 (1 Cycle=28 days)

  • Time to Maximum Observed Plasma Concentration (Tmax) of Venetoclax

    Baseline up to Cycle 6 (1 Cycle=28 days)

  • Maximal Plasma Concentration (Cmax) of Venetoclax

    Baseline up to Cycle 6 (1 Cycle=28 days)

  • +12 more secondary outcomes

Study Arms (6)

Dose-Finding: Schedule A: Relapsed/Refractory CLL

EXPERIMENTAL

All 4 cohorts will begin venetoclax administration after the ramp-up period of 5 weeks. In 4 cohorts of participants with relapsed/refractory CLL escalating doses of venetoclax will be administered in combination with fixed dose obinutuzumab in the dose-finding stage. In Schedule A, venetoclax will be introduced before obinutuzumab. Schedule A will be explored prior to Schedule B.

Drug: ObinutuzumabDrug: Venetoclax

Dose-Finding: Schedule B: Relapsed/Refractory CLL

EXPERIMENTAL

In 4 cohorts of participants with relapsed/refractory CLL escalating doses of venetoclax will be administered in combination with fixed dose obinutuzumab in the dose-finding stage. In Schedule B, venetoclax will be introduced after obinutuzumab. Schedule A will be explored prior to Schedule B.

Drug: ObinutuzumabDrug: Venetoclax

Dose-Finding: Schedule A: Previously Untreated CLL

EXPERIMENTAL

All 4 cohorts will begin venetoclax administration after the ramp-up period of 5 weeks. In 4 cohorts of participants with previously untreated CLL escalating doses of venetoclax will be administered in combination with fixed dose obinutuzumab in the dose-finding stage. In Schedule A, venetoclax will be introduced before obinutuzumab. Schedule A will be explored prior to Schedule B.

Drug: ObinutuzumabDrug: Venetoclax

Dose-Finding: Schedule B: Previously Untreated CLL

EXPERIMENTAL

In 4 cohorts of participants with previously untreated CLL escalating doses of venetoclax will be administered in combination with fixed dose obinutuzumab in the dose-finding stage. In Schedule B, venetoclax will be introduced after obinutuzumab. Schedule A will be explored prior to Schedule B.

Drug: ObinutuzumabDrug: Venetoclax

Safety Expansion: Relapsed/Refractory CLL

EXPERIMENTAL

In participants with relapsed/refractory CLL a recommended dose of venetoclax will be administered in combination with obinutuzumab in the safety expansion stage. Schedule A or B will be used for the expansion cohort after a review of available safety data from the dose finding stage.

Drug: ObinutuzumabDrug: Venetoclax

Safety Expansion: Previously Untreated CLL

EXPERIMENTAL

In participants with previously untreated CLL a recommended dose of venetoclax will be administered in combination with obinutuzumab in the safety expansion stage. Schedule A or B will be used for the expansion cohort after a review of available safety data from the dose finding stage.

Drug: ObinutuzumabDrug: Venetoclax

Interventions

ObinutuzumabDRUG

Participants will receive IV infusion of obinutuzumab 100 milligrams (mg) on Day 1 of Cycle 1, 900 mg on Day 2 of Cycle 1, and 1000 mg on Days 8 and 15 of Cycle 1 and on Day 1 of Cycles 2-6.

Also known as: GA101; RO5072759
Dose-Finding: Schedule A: Previously Untreated CLLDose-Finding: Schedule A: Relapsed/Refractory CLLDose-Finding: Schedule B: Previously Untreated CLLDose-Finding: Schedule B: Relapsed/Refractory CLLSafety Expansion: Previously Untreated CLLSafety Expansion: Relapsed/Refractory CLL
VenetoclaxDRUG

Participants will receive multiple doses of venetoclax orally once daily.

Also known as: ABT-199, GDC-0199
Dose-Finding: Schedule A: Previously Untreated CLLDose-Finding: Schedule A: Relapsed/Refractory CLLDose-Finding: Schedule B: Previously Untreated CLLDose-Finding: Schedule B: Relapsed/Refractory CLLSafety Expansion: Previously Untreated CLLSafety Expansion: Relapsed/Refractory CLL

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Diagnosis of relapsing/refractory or previously untreated chronic lymphocytic leukemia
  • Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to (\</=) 1
  • Adequate bone marrow function
  • Adequate coagulation, renal and hepatic function
  • For all participants, agreement to remain abstinent or use contraceptive methods that result in a failure rate of less than (\<) 1% per year during the treatment period and for at least 90 days (30 days for women) after the last dose of venetoclax or 18 months after the last dose of obinutuzumab, whichever is longer

You may not qualify if:

  • Participants who have undergone allogenic stem cell transplant are ineligible unless they meet the following criteria, a) participants who are off all immunosuppressive therapy, b) participants who have no signs and/or symptoms of acute or chronic graft versus host disease, or c) participants must have appropriate hematology counts
  • Infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
  • Uncontrolled autoimmune hemolytic anemia or thrombocytopenia
  • Investigational or anti-cancer therapy within 5 half-lives prior to the first dose of study drug
  • History of significant renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, cardiovascular, or hepatic disease

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (10)

UCSD Moores Cancer Center

La Jolla, California, 92093, United States

Location

Colorado Blood Cancer Institute (CBCI) at Presbyterian/ St. Luke's Medical Center

Denver, Colorado, 80218, United States

Location

Weill Cornell Medical College-New York Presbyterian Hospital

New York, New York, 10021, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Oncology Associates of Oregon

Springfield, Oregon, 97477, United States

Location

SCRI-Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

The Methodist Hospital Research Institute; Academic Office of Clinical Trials

Houston, Texas, 77030, United States

Location

St James University Hospital

Leeds, LS9 7TF, United Kingdom

Location

Leicester Royal Infirmary NHS Trust

Leicester, LE1 5WW, United Kingdom

Location

Barts and The London School of Medicine and Dentistry; Queen Mary, University of London

London, E1 2AD, United Kingdom

Location

Related Publications (2)

  • Samineni D, Gibiansky L, Wang B, Vadhavkar S, Rajwanshi R, Tandon M, Sinha A, Al-Sawaf O, Fischer K, Hallek M, Salem AH, Li C, Miles D. Pharmacokinetics and Exposure-Response Analysis of Venetoclax + Obinutuzumab in Chronic Lymphocytic Leukemia: Phase 1b Study and Phase 3 CLL14 Trial. Adv Ther. 2022 Aug;39(8):3635-3653. doi: 10.1007/s12325-022-02170-w. Epub 2022 Jun 16.

    PMID: 35708885DERIVED

  • Flinn IW, Gribben JG, Dyer MJS, Wierda W, Maris MB, Furman RR, Hillmen P, Rogers KA, Iyer SP, Quillet-Mary A, Ysebaert L, Walter HS, Verdugo M, Klein C, Huang H, Jiang Y, Lozanski G, Pignataro DS, Humphrey K, Mobasher M, Kipps TJ. Phase 1b study of venetoclax-obinutuzumab in previously untreated and relapsed/refractory chronic lymphocytic leukemia. Blood. 2019 Jun 27;133(26):2765-2775. doi: 10.1182/blood-2019-01-896290. Epub 2019 Mar 12.

    PMID: 30862645DERIVED

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

obinutuzumabvenetoclax

Condition Hierarchy (Ancestors)

Leukemia, B-CellLeukemia, LymphoidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Clinical Trials

    Genentech, Inc.

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 12, 2012

First Posted

September 14, 2012

Study Start

November 29, 2012

Primary Completion

May 21, 2018

Study Completion

August 23, 2019

Last Updated

January 10, 2020

Record last verified: 2020-01

Locations

US(7)GB(3)