A Phase II Study of Idelalisib (GS1101, CAL101) + Ofatumumab in Previously Untreated Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Leukemia (SLL)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 27
- 试验地点
- 3
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
This research study is evaluating a combination of drugs called Ofatumumab and Idelalisib as a possible treatment for Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Leukemia (SLL).
The main purpose of this study is to examine the combination of the two drugs, Ofatumumab and Idelalisib, in participants who have been diagnosed with CLL/SLL and have not previously received treatment but do require treatment. The investigators hope to observe how participants' disease will be impacted by this treatment and whether they will benefit more from combining these drugs together rather than taking them separately. Both of these drugs have been used in treatment for CLL / SLL and information from those research studies suggests that these drugs may help patients with CLL/SLL.
Ofatumumab is an antibody engineered in the lab against CD20, a protein on the surface of CLL cells, which is expressed in CLL. An antibody is a molecule your body creates to identify foreign substances so that it can destroy them. Ofatumumab has been FDA approved for treatment of CLL/SLL that has relapsed or progressed on other therapies. Idelalisib is a drug that blocks one of the signals inside the cells that cause this type of cancer to grow and survive. The investigators hope that combining Ofatumumab with Idelalisib will stop the growth of disease.
In this research study, the investigators are evaluating the side effects of combining these two drugs, gathering information on the CLL/SLL disease process and how the study affects the patient's cells, as well as assessing the outcome of the disease. This combination of drugs has been previously tested, and appeared to be well tolerated.
详细描述
Before the research starts (screening): After signing the consent form, the participant will be asked to undergo some screening tests or procedures to find out if they are eligible to be in this research study. Many of these tests and procedures are likely to be part of regular cancer care and may be done even if it turns out that the participant does not take part in the research study. If the participant has had some of these tests or procedures recently, they may or may not have to be repeated.
- A medical history, which includes questions about the participant's health, current medications, and any allergies.
- Physical examination, which includes vital signs, height, weight, and disease assessment by the size of the participant's spleen, liver, and lymph nodes.
- Performance status, which evaluates how the participant is able to carry on with their usual activities.
- An assessment of the patient's tumor by CT (Computerized Tomography) scan, MRI or PET (Positron Emission Tomography) scans,
- Bone marrow aspirate and biopsy: A study tube (plastic cylinder container that contains biopsy material) will be drawn during this biopsy to further assess the participant's disease status.
- Blood tests, a maximum of 24 teaspoons will be collected.
- Urine test.
- A blood pregnancy test
- A Hepatitis B and C test, will require blood sample.
If these tests show that the participant is eligible to participate in the research study, then the participant will be begin will begin the study treatment. If you do not meet the eligibility criteria, the participant will not be able to participate in this research study.
Additional research procedures to be performed at the time of screening:
• Blood tests, including baseline tests so that the investigators can measure any additional effect of the study drug and disease status
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Participants must meet the following criteria on screening examination to be eligible to participate in the study:
- •Subjects must have CLL / SLL, as documented by a history at some point of an absolute peripheral blood B cell count > 5000, with a monoclonal B cell population co-expressing CD19, CD5, and CD23, or if CD23 negative, then documentation of the absence of t(11;14) or cyclin D1 overexpression. Alternatively patients with lymphadenopathy in the absence of circulating disease will also be eligible for this study if lymph node biopsy establishes the diagnosis of CLL with the above immunophenotype.
- •Participants must have measurable disease (lymphocytosis > 5,000, or palpable or CT measurable lymphadenopathy > 1.5 cm, or bone marrow involvement >30%).
- •Subjects must not have received any prior systemic therapy for CLL and currently have an indication for treatment as defined by the IWCLL 2008 Guidelines:
- •Massive or progressive splenomegaly; OR
- •Massive lymph nodes, nodal clusters, or progressive lymphadenopathy; OR
- •Grade 2 or 3 fatigue; OR
- •Fever ≥ 100.5°F or night sweats for greater than 2 weeks without documented infection; OR
- •Presence of weight loss ≥ 10% over the preceding 6 months; OR
- •Progressive lymphocytosis with an increase of ≥ 50% over a 2-month period or an anticipated doubling time of less than 6 months; OR
- •Evidence of progressive marrow failure as manifested by the development of or worsening of anemia and or thrombocytopenia.
- •ECOG performance status <2 (see Appendix A).
- •Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of idelalisib or ofatumumab in participants <18 years of age, children are excluded from this study.
- •Participants must have normal organ and marrow function as defined below:
- •creatinine <2.0 times upper normal limit, total bilirubin <1.5 times upper normal limit (unless due to disease involvement of liver, hemolysis or a known history of Gilbert's disease)
- •ALT <2.5 times upper normal limit (unless due to disease involvement of liver) alkaline phosphatase <2.5 times upper normal limit (unless due to disease involvement of the liver or bone marrow)
- •Ability to understand and the willingness to sign a written informed consent document.
排除标准
- •Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study.
- •Participants who have had any prior systemic therapy for CLL, or chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) for some other indication prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- •History of severe allergic reactions attributed to compounds of similar chemical or biologic composition to ofatumumab or idelalisib.
- •Subjects who have current active hepatic or biliary disease (with exception of participants with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
- •Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half lives or 4 weeks prior to enrollment, whichever is longer, or currently participating in any other interventional clinical study
- •Other past or current malignancy that could interfere with the interpretation of outcome. Subjects who have been free of active malignancy for at least 2 years, or have a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma, or whose malignancy will not interfere with the interpretation of study results, are eligible.
- •Chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active Hepatitis C.
- •History of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae
- •Known HIV positive. HIV-positive individuals on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with idelalisib. In addition, these individuals are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.
- •Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to randomization, congestive heart failure (NYHA III-IV), and arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction abnormalities.
- •Significant concurrent, uncontrolled medical condition 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 participant.
- •Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HB DNA test will be performed and if positive the subject will be excluded.
- •If HBV DNA is negative, subject may be included but must undergo HBV DNA PCR testing at least every 2 months from the start of treatment until 12 months post treatment. Prophylactic antiviral therapy may be initiated at the discretion of the investigator.
- •Positive serology for hepatitis C (HC) defined as a positive test for HepC Ab, in which case reflexively perform an HC RIBA immunoblot assay or hepatitis C viral load to confirm the result. If the confirmatory test is negative the subject will be eligible.
- •Pregnant or lactating women.
- •Women of childbearing potential, including women whose last menstrual period was less than one year prior to screening, unable or unwilling to use adequate contraception from study start to 30 days after the last dose of protocol therapy. Adequate contraception is defined as hormonal birth control, intrauterine device, double barrier method or total abstinence.
- •Male subjects unable or unwilling to use adequate contraception methods from study start to 30 days after the last dose of protocol therapy.
- •Participants using concomitant corticosteroids are allowed as long as the subject is on the equivalent of 20mg/day or less of prednisone and has been on a stable dose for at least two weeks prior to initiating therapy.
研究组 & 干预措施
Idelalisib & Ofatumumab
Idelalisib will be given orally continuously at 150 mg BID. On day 57, ofatumumab will begin with the 300 mg dose, given after idelalisib is taken. Ofatumumab will then be administered at 1000 mg weekly to complete 8 weeks (days 64, 71, 78, 85, 92, 99, 106) throughout Cycles 3 and 4. This will be followed by monthly ofatumumab on weeks 20, 24, 28, 32 to complete 4 additional cycles (5-8). The overall induction treatment period will then be 8 months, comprised of two months of single agent idelalisib followed by 6 months of ofatumumab with idelalisib. After the completion of the induction treatment, idelalisib will continue indefinitely in arbitrarily defined 28 day cycles in all participants who have not had excessive toxicity and do not have progressive disease.
干预措施: Idelalisib (Drug)
Idelalisib & Ofatumumab
Idelalisib will be given orally continuously at 150 mg BID. On day 57, ofatumumab will begin with the 300 mg dose, given after idelalisib is taken. Ofatumumab will then be administered at 1000 mg weekly to complete 8 weeks (days 64, 71, 78, 85, 92, 99, 106) throughout Cycles 3 and 4. This will be followed by monthly ofatumumab on weeks 20, 24, 28, 32 to complete 4 additional cycles (5-8). The overall induction treatment period will then be 8 months, comprised of two months of single agent idelalisib followed by 6 months of ofatumumab with idelalisib. After the completion of the induction treatment, idelalisib will continue indefinitely in arbitrarily defined 28 day cycles in all participants who have not had excessive toxicity and do not have progressive disease.
干预措施: Ofatumumab (Drug)
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: Disease evaluated on Cycle 2 day 22 (Restage end of cycle 2), Cycle 10 day 1 (Final Restage 2 months after end of ofa therapy) and off treatment prior to cycle 10. Treatment duration is median 243 days with range of 9-620 days.
The overall response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on IWCLL 2008 criteria.
次要结局
- Complete Response Rate (CRR)(Disease evaluated on Cycle 2 day 22 (Restage end of cycle 2), Cycle 10 day 1 (Final Restage 2 months after end of ofa therapy) and off treatment prior to cycle 10. Treatment duration is median 243 days with range of 9-620 days.)
- Median Progression-Free Survival (PFS)(Disease evaluated on Cycle 2 day 22, Cycle 10 day 1 and off treatment prior to cycle 10. In long term, survival follow-up yearly. The median follow up time among survivors was 32.2 months (range 13, 35).)
研究者
Jennifer R. Brown, MD, PhD
Sponsor Investigator
Dana-Farber Cancer Institute