Trial Outcomes & Findings for A Dose-Finding and Efficacy Study of Venetoclax, CC-486, and Obinutuzumab in Follicular Lymphoma (NCT NCT04722601)

NCT ID: NCT04722601

Last Updated: 2024-05-16

Results Overview

The maximum tolerated dose of venetoclax and CC-486 in patients with minimally pre-treated follicular lymphoma. Doctors leading the study will find the maximum tolerated dose by assessing the rate of serious side effects (known as "dose limiting toxicities") according to the NCI Common Terminology Criteria (CTCAE) for Adverse Events Version 5.

• Recruitment status: TERMINATED
• Study phase: PHASE1/PHASE2
• Target enrollment: 2 participants
• Primary outcome timeframe: 336 days (the duration of phase 1 treatment)
• Results posted on: 2024-05-16

Participant Flow

Study was terminated. Only 2 participants were enrolled at the starting dose.

Participant milestones

Measure	Phase 1(Dose-Finding Arm): Group 1 - Dose Level 1 / Starting Dose Phase 1/the dose-finding arm of this study will use three dose levels (a starting dose, second dose and highest dose) of the venetoclax, CC-486 and obinutuzumab regimen. If participants in group 1 don't experience severe negative side effects to the starting dose of the regimen, then more participants will be assigned to groups 2 and 3 to take higher doses until the safest/ most tolerable dose is found. Group 1/ Dose Level 1: Participants in group 1 will receive a three-drug regimen of venetoclax, CC-486, and obinutuzumab at a starting dose used in previous human studies. Participants in this group will receive: * Venetoclax: 400 mg on days 1-28 * CC-486: 200 mg on days 1-14 * Obinutuzumab: 1000 mg on days 1, 8 and 15 of cycle 1, and on day 1 of each following cycle. Treatment using these three study drugs (venetoclax, CC-486, and obinutuzumab) will be given in 12 consecutive cycles that run for 28 days during each cycle (336 days).
Overall Study STARTED	2
Overall Study COMPLETED	2
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Dose-Finding and Efficacy Study of Venetoclax, CC-486, and Obinutuzumab in Follicular Lymphoma

Baseline characteristics by cohort

Measure	Phase 1(Dose-Finding Arm): Group 1 - Dose Level 1 / Starting Dose n=2 Participants Phase 1/the dose-finding arm of this study will use three dose levels (a starting dose, second dose and highest dose) of the venetoclax, CC-486 and obinutuzumab regimen. If participants in group 1 don't experience severe negative side effects to the starting dose of the regimen, then more participants will be assigned to groups 2 and 3 to take higher doses until the safest/ most tolerable dose is found. Group 1/ Dose Level 1: Participants in group 1 will receive a three-drug regimen of venetoclax, CC-486, and obinutuzumab at a starting dose used in previous human studies. Participants in this group will receive: * Venetoclax: 400 mg on days 1-28 * CC-486: 200 mg on days 1-14 * Obinutuzumab: 1000 mg on days 1, 8 and 15 of cycle 1, and on day 1 of each following cycle. Treatment using these three study drugs (venetoclax, CC-486, and obinutuzumab) will be given in 12 consecutive cycles that run for 28 days during each cycle (336 days).
Age, Continuous	68.3 years STANDARD_DEVIATION 16.1 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Race/Ethnicity, Customized White	1 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: 336 days (the duration of phase 1 treatment)

Population: Data not collected

The maximum tolerated dose of venetoclax and CC-486 in patients with minimally pre-treated follicular lymphoma. Doctors leading the study will find the maximum tolerated dose by assessing the rate of serious side effects (known as "dose limiting toxicities") according to the NCI Common Terminology Criteria (CTCAE) for Adverse Events Version 5.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 336 days (duration of phase 1 treatment)

Population: Data not collected

The number of participants who discontinue the three-drug regimen of venetoclax, CC-486, and obinutuzumab during phase 1 of the study due to serious side effects (grade 3/4) as assessed by the NCI Common Terminology Criteria (CTCAE) for Adverse Events Version 5.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 336 days (duration of phase 1 treatment)].

Population: Data not collected

The number of participants who report serious side effects in response to the three-drug regimen of venetoclax, CC-486 and obinutuzumab during phase 1 treatment. Serious side effects will be defined as grade 3/ 4 according to criteria set by the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 5.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 336 days (duration of phase 1 treatment)

Population: Data not collected

The number of participants who do not show detectable signs of cancer (also known as "complete response") after taking combined CC-486 and obinutuzumab as assessed by positron emission tomography (PET scan) based on Lugano criteria.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 55 months (at study conclusion) and 5 years after end of study

Population: Data not collected

The length of time that half of the participants in the expansion/phase II study group are alive after taking the maximum tolerated dose established in the first phase of the study. This time, also known as "median overall survival," will be documented at the end of the study and five years after study completion.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 55 months (at study conclusion) and 5 years after end of study

Population: Data not collected

The average length of time study participants in the expansion/phase II group of the study live with follicular lymphoma, but it does not get worse (also known as "median progression-free survival" of participants). This time will be assessed at the conclusion of study and five years after study completion.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 84 days (three cycles of combined oral therapies venetoclax and CC-486 oral

Population: Data not collected

Number of participants in phase II group who do not show signs of follicular lymphoma after receiving three cycles of venetoclax + CC-486 (combined oral therapy). This will be assessed by positron emission tomography (PET scan) based on Lugano criteria.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 30 months and 336 days (treatment period); approximately 3.4 years

Population: Data not collected

Number of participants who do not show signs of follicular lymphoma (also known as "complete response rate") 30 months after starting treatment. This will be assessed by positron emission tomography (PET scan) based on Lugano criteria.

Outcome measures

Outcome data not reported

Adverse Events

Phase 1(Dose-Finding Arm): Group 1 - Dose Level 1 / Starting Dose

Serious events: 1 serious events

Other events: 2 other events

Deaths: 1 deaths

Serious adverse events

Measure

Phase 1(Dose-Finding Arm): Group 1 - Dose Level 1 / Starting Dose n=2 participants at risk Phase 1/the dose-finding arm of this study will use three dose levels (a starting dose, second dose and highest dose) of the venetoclax, CC-486 and obinutuzumab regimen. If participants in group 1 don't experience severe negative side effects to the starting dose of the regimen, then more participants will be assigned to groups 2 and 3 to take higher doses until the safest/ most tolerable dose is found. Group 1/ Dose Level 1: Participants in group 1 will receive a three-drug regimen of venetoclax, CC-486, and obinutuzumab at a starting dose used in previous human studies. Participants in this group will receive: * Venetoclax: 400 mg on days 1-28 * CC-486: 200 mg on days 1-14 * Obinutuzumab: 1000 mg on days 1, 8 and 15 of cycle 1, and on day 1 of each following cycle. Treatment using these three study drugs (venetoclax, CC-486, and obinutuzumab) will be given in 12 consecutive cycles that run for 28 days during each cycle (336 days).

Investigations Neutrophil count decreased

50.0% 1/2 • 10 months

Other adverse events

Measure	Phase 1(Dose-Finding Arm): Group 1 - Dose Level 1 / Starting Dose n=2 participants at risk Phase 1/the dose-finding arm of this study will use three dose levels (a starting dose, second dose and highest dose) of the venetoclax, CC-486 and obinutuzumab regimen. If participants in group 1 don't experience severe negative side effects to the starting dose of the regimen, then more participants will be assigned to groups 2 and 3 to take higher doses until the safest/ most tolerable dose is found. Group 1/ Dose Level 1: Participants in group 1 will receive a three-drug regimen of venetoclax, CC-486, and obinutuzumab at a starting dose used in previous human studies. Participants in this group will receive: * Venetoclax: 400 mg on days 1-28 * CC-486: 200 mg on days 1-14 * Obinutuzumab: 1000 mg on days 1, 8 and 15 of cycle 1, and on day 1 of each following cycle. Treatment using these three study drugs (venetoclax, CC-486, and obinutuzumab) will be given in 12 consecutive cycles that run for 28 days during each cycle (336 days).
Investigations Alkaline phosphatase increased	50.0% 1/2 • 10 months
Metabolism and nutrition disorders Anorexia	50.0% 1/2 • 10 months
Musculoskeletal and connective tissue disorders Arthralgia	50.0% 1/2 • 10 months
Investigations Aspartate aminotransferase increased	50.0% 1/2 • 10 months
Respiratory, thoracic and mediastinal disorders Aspiration	50.0% 1/2 • 10 months
Investigations Blood lactate dehydrogenase increased	50.0% 1/2 • 10 months
Gastrointestinal disorders Constipation	50.0% 1/2 • 10 months
Gastrointestinal disorders Diarrhea	50.0% 1/2 • 10 months
Nervous system disorders Dysgeusia	50.0% 1/2 • 10 months
General disorders Fatigue	50.0% 1/2 • 10 months
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	50.0% 1/2 • 10 months
Metabolism and nutrition disorders Hyperglycemia	50.0% 1/2 • 10 months
Investigations Lymphocyte count decreased	50.0% 1/2 • 10 months
Gastrointestinal disorders Nausea	50.0% 1/2 • 10 months
Investigations Neutrophil count decreased	100.0% 2/2 • 10 months
Skin and subcutaneous tissue disorders Rash acneiform	50.0% 1/2 • 10 months
Gastrointestinal disorders Vomiting	50.0% 1/2 • 10 months
Investigations White blood cell decreased	50.0% 1/2 • 10 months
Respiratory, thoracic and mediastinal disorders Cough	50.0% 1/2 • 10 months

Additional Information

Dr. Sonali Smith

University of Chicago

Phone: 855-702-8222

Email: smsmith@bsd.uchicago.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place