A Phase II Study of Ofatumumab-High Dose Methylprednisolone Followed by Ofatumumab-Alemtuzumab in 17p Deletion CLL
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Induction Overall Response Rate (ORR)
研究概览
简要总结
The main purpose of this study is to examine how two separate groups of 17p deletion Chronic lymphocytic leukemia (CLL) participants respond to sequential treatment with this particular combination of drugs. The two groups are those participants who have previously received treatment for their CLL and those who have not yet received any treatment. The combination of drugs is Ofatumumab and High-Dose Methylprednisolone (HDMP) first followed by Ofatumumab and Alemtuzumab. All three drugs are FDA approved and have known activity in treating 17p CLL. We hope that by combining these drugs together in this study, they will have more benefit than each one alone and that the subjects' CLL will be significantly impacted.
详细描述
Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy.
Part A: Ofatumumab + HDMP 2-4 cycles Part B: Ofatumumab + Alemtuzumab 1-6 cycles Part C: Maintenance with Ofatumumab + Alemtuzumab up to 2 years
Between days 15-22 of Cycle 2 of Part A, participants are restaged. Participants who achieve nodal complete response discontinue Part A therapy and undergo minimal residual disease (MRD) assessment to guide the decision whether to go to Part B or Part C. The participants with persistent disease after 2 cycles of Part A therapy receive 2 more cycles of Part A therapy and then undergo another restaging as well as MRD assessment. At restaging, participants with minimal disease are eligible for Part C or allogeneic stem cell transplant (SCT) off protocol. The remaining participants receive Part B therapy. On Part B, restaging occurs at weeks 12 and 18. If MRD negative complete response (CR) status is achieved then therapy is discontinued and the primary endpoint evaluation occurs 2 months later. Otherwise with persistent disease Part B therapy continues up to 24 weeks and the primary endpoint evaluation occurs after Part B therapy is completed. Participants who achieve clinical complete response may receive Part C therapy or be observed while waiting SCT.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Documented CLL/SLL
- •17p deletion by FISH in 20% or more nuclei on peripheral blood, bone marrow or lymph node
- •Normal organ function
排除标准
- •Pregnant or breast feeding
- •Current active hepatic or biliary disease
- •Chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, tuberculosis and active Hepatitis C
- •History of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae
- •Other past or current malignancy. Participants who have been free of malignancy for at least 2 years, or who have a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.
- •Known HIV positive
- •Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months prior to study entry, congestive heart failure, and arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction abnormalities.
- •Significant concurrent uncontrolled medical conditions including, but not limited to, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease which in the opinion of the investigator may represent a risk for the subject.
- •Positive serology for Hepatitis B or C
- •History of allergic reactions attributed to ofatumumab.
研究组 & 干预措施
Treatment Naive
Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days):
Induction Part A: Ofatumumab + HDMP 2-4 cycles
Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22
High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3
Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy.
Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles
Ofatumumab: 1000 mg IV Day 1
Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26
Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study.
Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles
Ofatumumab: 1000 mg IV Day 1 every other cycle
Alemtuzumab: 30 mg subcutaneously Days 14, 28
干预措施: Ofatumumab (Drug)
Treatment Naive
Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days):
Induction Part A: Ofatumumab + HDMP 2-4 cycles
Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22
High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3
Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy.
Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles
Ofatumumab: 1000 mg IV Day 1
Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26
Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study.
Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles
Ofatumumab: 1000 mg IV Day 1 every other cycle
Alemtuzumab: 30 mg subcutaneously Days 14, 28
干预措施: High-Dose Methylprednisolone (Drug)
Treatment Naive
Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days):
Induction Part A: Ofatumumab + HDMP 2-4 cycles
Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22
High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3
Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy.
Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles
Ofatumumab: 1000 mg IV Day 1
Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26
Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study.
Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles
Ofatumumab: 1000 mg IV Day 1 every other cycle
Alemtuzumab: 30 mg subcutaneously Days 14, 28
干预措施: Alemtuzumab (Drug)
Relapsed/Refractory
Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days):
Induction Part A: Ofatumumab + HDMP 2-4 cycles
Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22
High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3
Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy.
Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles
Ofatumumab: 1000 mg IV Day 1
Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26
Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study.
Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles
Ofatumumab: 1000 mg IV Day 1 every other cycle
Alemtuzumab: 30 mg subcutaneously Days 14, 28
干预措施: Ofatumumab (Drug)
Relapsed/Refractory
Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days):
Induction Part A: Ofatumumab + HDMP 2-4 cycles
Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22
High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3
Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy.
Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles
Ofatumumab: 1000 mg IV Day 1
Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26
Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study.
Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles
Ofatumumab: 1000 mg IV Day 1 every other cycle
Alemtuzumab: 30 mg subcutaneously Days 14, 28
干预措施: High-Dose Methylprednisolone (Drug)
Relapsed/Refractory
Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days):
Induction Part A: Ofatumumab + HDMP 2-4 cycles
Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22
High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3
Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy.
Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles
Ofatumumab: 1000 mg IV Day 1
Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26
Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study.
Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles
Ofatumumab: 1000 mg IV Day 1 every other cycle
Alemtuzumab: 30 mg subcutaneously Days 14, 28
干预措施: Alemtuzumab (Drug)
结局指标
主要结局
Induction Overall Response Rate (ORR)
时间窗: Disease was evaluated after weeks 8 and 16 of Part A and at 12, 18 and 24 weeks during part B.
Induction ORR is the percentage of participants achieving a minimum of partial response (PR) over induction treatment based on International Workshop on Chronic Lymphocytic Leukemia (IW-CLL) criteria (Hallek, et al 2008). There are numerous diagnostic tests used for response evaluation including potentially CBC and differential count, marrow aspirate and biopsy, ultrasound of the abdomen, CT scans (chest, pelvis, abdomen) and physical examination. PR is a 50% or greater decrease of measured size of lymphadenopathy, hepatomegaly, splenomegaly as well as blood lymphocytes (over baseline), marrow infiltrate or B-lymphoid nodules and a 50% or greater increase from baseline in platelet count (or level \>100,000/micro liter), hemoglobin (or level \>11 grams/deciliter), neutrophils (or level \>1500/microliter).
次要结局
- Number of Participants Achieving Induction Complete Response (CR)(Disease was evaluated after weeks 8 and 16 of Part A and at 12, 18 and 24 weeks during part B.)
- Overall Objective Response Rate (ORR)(Disease was evaluated after weeks 8 and 16 of Part A, at 12, 18 and 24 weeks during part B and every 6 months on Part C.)
- Number of Participants With Overall CR(Disease was evaluated after weeks 8 and 16 of Part A, at 12, 18 and 24 weeks during part B and every 6 months on Part C.)
- Number of Participants Completing Part A Treatment(Evaluated up to 4 cycles/16 weeks.)
- Overall MRD Negative Rate(MRD was assessed after weeks 8 and 16 of Part A, at 12, 18 and 24 weeks during part B and every 6 months on Part C.)
- Transplant Rate(Evaluated up to 36 cycles (approximately 2.75 years) of treatment (Parts A, B and C))
- Number of Participants With Treatment-Related Grades 1-3 Hyperglycemia During Part A Induction(Adverse Events (AEs) were collected weekly during cycle 1 Part A and then every other week for the duration of Part A (up to 16 weeks))
- 3-Year Progression-Free Survival (PFS) Probability(Disease was evaluated on treatment after weeks 8 and 16 of Part A, at 12, 18 and 24 weeks during part B and every 6 months on Part C as well as off-treatment every 3 months up to 5 years.)
- 3-year Overall Survival (OS) Probability(Median survival follow-up was 45 months (range 31-58 months) in this study cohort.)
- Number of Participants Completing Only 2 Cycles of Part A Treatment(Evaluated after 2 cycles/8 weeks of Part A therapy.)
研究者
Jennifer R. Brown, MD, PhD
Principal Investigator
Dana-Farber Cancer Institute