A Multicenter, Single-Arm, Phase I/II Dose Finding and Efficacy Study of Venetoclax, CC-486, and Obinutuzumab in Minimally-Pretreated Follicular Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 1
- 主要终点
- Phase I Objective: Maximum Tolerated Dose of Venetoclax and CC-486 As Assessed by Rate of Reported Dose Limiting Toxicities (Side Effects) According to CTCAE Criteria Version 5
研究概览
简要总结
This study focuses on finding a safe and tolerable dose for a three-drug regimen that combines venetoclax (Venclexta Ⓡ), CC-486 (also known as oral azacitidine) and obinutuzumab (Gazyva Ⓡ) to treat cancer participants who have minimally pretreated follicular lymphoma and have experienced disease progression despite trying previous cancer therapies. If a safe and tolerable drug dose can be found in the first phase of the study, doctors leading the study will launch a second phase of the study within an expansion cohort. Participants in this expansion cohort will receive the dose established in the first phase of the study to determine the efficacy of the regimen/ established dose. Participants in the expansion cohort will also receive the same study drugs from the first phase of the study, but in a different order/combination (first pairing the two oral drugs, CC-486 and venetoclax, then adding the third drug, obinutuzumab to treatment). The end goal of this research is to establish a new chemotherapy-sparing treatment option for patients with follicular lymphoma that is just as effective (or better) than current standard of care options.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
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).
干预措施: Venetoclax (Drug)
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).
干预措施: Obinutuzumab (Drug)
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).
干预措施: CC-486 (Drug)
Phase 2 (Efficacy Arm/ Expansion Cohort)
Participants in this arm will help test the efficacy of the three-drug regimen and dose established in the phase 1 of the study. Participants will take two drugs (venetoclax and CC-48) used in the same three-drug regimen during the first phase of this study. These two drugs will be paired together by themselves and given to participants in the expansion cohort before obinutuzumab (a third drug) is added during cycle 4 of treatment.
干预措施: Venetoclax (Drug)
Phase 2 (Efficacy Arm/ Expansion Cohort)
Participants in this arm will help test the efficacy of the three-drug regimen and dose established in the phase 1 of the study. Participants will take two drugs (venetoclax and CC-48) used in the same three-drug regimen during the first phase of this study. These two drugs will be paired together by themselves and given to participants in the expansion cohort before obinutuzumab (a third drug) is added during cycle 4 of treatment.
干预措施: Obinutuzumab (Drug)
Phase 2 (Efficacy Arm/ Expansion Cohort)
Participants in this arm will help test the efficacy of the three-drug regimen and dose established in the phase 1 of the study. Participants will take two drugs (venetoclax and CC-48) used in the same three-drug regimen during the first phase of this study. These two drugs will be paired together by themselves and given to participants in the expansion cohort before obinutuzumab (a third drug) is added during cycle 4 of treatment.
干预措施: CC-486 (Drug)
Phase 1(Dose-Finding Arm): Group 2 - Dose Level 2 /Second Dose
Participants in group 2 will receive a three-drug regimen of venetoclax, CC-486, and obinutuzumab at the second highest dose (dose level 2) set by doctors leading the study. Participants in this group will receive:
- Venetoclax:
600 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).
干预措施: Venetoclax (Drug)
Phase 1(Dose-Finding Arm): Group 2 - Dose Level 2 /Second Dose
Participants in group 2 will receive a three-drug regimen of venetoclax, CC-486, and obinutuzumab at the second highest dose (dose level 2) set by doctors leading the study. Participants in this group will receive:
- Venetoclax:
600 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).
干预措施: Obinutuzumab (Drug)
Phase 1(Dose-Finding Arm): Group 2 - Dose Level 2 /Second Dose
Participants in group 2 will receive a three-drug regimen of venetoclax, CC-486, and obinutuzumab at the second highest dose (dose level 2) set by doctors leading the study. Participants in this group will receive:
- Venetoclax:
600 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).
干预措施: CC-486 (Drug)
Phase 1 (Dose-Finding Arm) - Group 3 - Dose Level 3/ Highest Dose
Participants in group 3 will receive a three-drug regimen of venetoclax, CC-486, and obinutuzumab at the highest dose (dose level 3) set by doctors leading the study. Participants in this group will receive:
- Venetoclax:
800 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).
干预措施: Venetoclax (Drug)
Phase 1 (Dose-Finding Arm) - Group 3 - Dose Level 3/ Highest Dose
Participants in group 3 will receive a three-drug regimen of venetoclax, CC-486, and obinutuzumab at the highest dose (dose level 3) set by doctors leading the study. Participants in this group will receive:
- Venetoclax:
800 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).
干预措施: Obinutuzumab (Drug)
Phase 1 (Dose-Finding Arm) - Group 3 - Dose Level 3/ Highest Dose
Participants in group 3 will receive a three-drug regimen of venetoclax, CC-486, and obinutuzumab at the highest dose (dose level 3) set by doctors leading the study. Participants in this group will receive:
- Venetoclax:
800 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).
干预措施: CC-486 (Drug)
Phase 1 (Dose-Finding Arm) - Group 4 - Lower Dose Level 1
Participants in this group will received a lower dose of the three-drug regimen using venetoclax, CC-486 and obinutuzumab set by doctors leading the study. Inclusion in this group is optional and based on whether the participant reports serious adverse events/side effects in response to a higher dose of the regimen. If participants are included in this group, they will receive:
- Venetoclax:
400 mg on days 1-28
- CC-486:
150 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.
干预措施: Venetoclax (Drug)
Phase 1 (Dose-Finding Arm) - Group 4 - Lower Dose Level 1
Participants in this group will received a lower dose of the three-drug regimen using venetoclax, CC-486 and obinutuzumab set by doctors leading the study. Inclusion in this group is optional and based on whether the participant reports serious adverse events/side effects in response to a higher dose of the regimen. If participants are included in this group, they will receive:
- Venetoclax:
400 mg on days 1-28
- CC-486:
150 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.
干预措施: Obinutuzumab (Drug)
Phase 1 (Dose-Finding Arm) - Group 4 - Lower Dose Level 1
Participants in this group will received a lower dose of the three-drug regimen using venetoclax, CC-486 and obinutuzumab set by doctors leading the study. Inclusion in this group is optional and based on whether the participant reports serious adverse events/side effects in response to a higher dose of the regimen. If participants are included in this group, they will receive:
- Venetoclax:
400 mg on days 1-28
- CC-486:
150 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.
干预措施: CC-486 (Drug)
Phase 1 (Dose-Finding Arm) - Group 5 - Lower Dose Level 2
Participants in this group will received the second lowest dose of the three-drug regimen using venetoclax, CC-486 and obinutuzumab set by doctors leading the study. Inclusion in this group is optional and based on whether the participant reports serious adverse events/side effects in response to a higher dose of the regimen. If participants are included in this group, they will receive:
- Venetoclax:
400 mg on days 1-10 only
- CC-486:
150 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.
干预措施: Venetoclax (Drug)
Phase 1 (Dose-Finding Arm) - Group 5 - Lower Dose Level 2
Participants in this group will received the second lowest dose of the three-drug regimen using venetoclax, CC-486 and obinutuzumab set by doctors leading the study. Inclusion in this group is optional and based on whether the participant reports serious adverse events/side effects in response to a higher dose of the regimen. If participants are included in this group, they will receive:
- Venetoclax:
400 mg on days 1-10 only
- CC-486:
150 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.
干预措施: Obinutuzumab (Drug)
Phase 1 (Dose-Finding Arm) - Group 5 - Lower Dose Level 2
Participants in this group will received the second lowest dose of the three-drug regimen using venetoclax, CC-486 and obinutuzumab set by doctors leading the study. Inclusion in this group is optional and based on whether the participant reports serious adverse events/side effects in response to a higher dose of the regimen. If participants are included in this group, they will receive:
- Venetoclax:
400 mg on days 1-10 only
- CC-486:
150 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.
干预措施: CC-486 (Drug)
结局指标
主要结局
Phase I Objective: Maximum Tolerated Dose of Venetoclax and CC-486 As Assessed by Rate of Reported Dose Limiting Toxicities (Side Effects) According to CTCAE Criteria Version 5
时间窗: 336 days (the duration of phase 1 treatment)
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.
Phase I Objective: Number of Participants Who Discontinue Venetoclax, CC-486 and Obinutuzumab Regimen Due to Reported Side Effects as Assessed by CTCAE Criteria Version 5
时间窗: 336 days (duration of phase 1 treatment)
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.
Phase I Objective: Number of Participants Taking Venetoclax, CC-486 and Obinutuzumab Who Report Serious Side Effects As Assessed by CTCAE Version 5
时间窗: 336 days (duration of phase 1 treatment)].
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.
4. Phase II Objective: Number of Participants Who Do Not Show Signs of Cancer After Taking CC-486 and Obinutuzumab (Oral Therapies) As Assessed by PET/CT Whole Body Scan (Based on Lugano Criteria)
时间窗: 336 days (duration of phase 1 treatment)
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.
次要结局
- Phase II Objective: The Length of Time That Half of Participants in the Expansion Group Are Alive After Receiving Phase 1 Dose of Treatment As Assessed at End of Study and 5 Years After Study is Complete(55 months (at study conclusion) and 5 years after end of study)
- Phase II Objective: Number of Participants Who Do Not Show Signs of Follicular Lymphoma After Venetoclax and CC-486 As Assessed by PET Scan (Based on Lugano Criteria)(84 days (three cycles of combined oral therapies venetoclax and CC-486 oral)
- Phase II Objective: Number of Participants Who Do Not Show Signs of Follicular Lymphoma 30 Months After Treatment As Assessed by PET Scan (Based on Lugano Criteria(30 months and 336 days (treatment period); approximately 3.4 years)
- Phase II Objective: The Average Length of Time Participants Treated at Phase 1 Dose Live With Follicular Lymphoma Without Symptoms of Cancer Worsening As Assessed at End of Study and 5 Years After Study is Complete(55 months (at study conclusion) and 5 years after end of study)