Study of Phosphatidylinositol-3-kinase (PI3K) Inhibitor Idelalisib (GS-1101) in Waldenström Macroglobulinemia

Study Overview
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Brief Summary
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This research study is evaluating a drug called idelalisib (formerly known as GS-1101 or CAL-101) as a possible treatment for Waldenstrom's Macroglobulinemia (WM).

Detailed Description
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This research study is a Phase II clinical trial. Phase II clinical trials test the effectiveness of an investigational drug, idelalisib, to learn whether idelalisib works in treating a specific cancer. Investigational means that idelalisib is still being studied and that research doctors are trying to find out more about it-such as the safest dose to use, the side effects it may cause, and if idelalisib is effective for treating different types of cancer. Idelalisib has already been approved in the US by the FDA to treat patients with relapsed chronic lymphocytic leukemia, follicular lymphoma and small lymphocytic lymphoma. Idelalisib is a newly discovered drug that is being developed as an anti-cancer agent. This drug has been used in laboratory experiments and other research studies in B-cell malignancies and information from those other research studies suggests that idelalisib may help to target the tumor cells in B-cell malignancies, including WM. B cells are a type of white blood cell responsible for making antibodies. In this research study, the investigators are testing the safety and efficacy of idelalisib as a treatment option for relapsed or refractory Waldenstrom's Macroglobulinemia.

Official Title
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Phase II Study of Phosphatidylinositol-3-kinase (PI3K) Inhibitor Idelalisib (GS-1101) in Waldenström Macroglobulinemia

Conditions
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Waldenstrom's Macroglobulinemia

Intervention / Treatment
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* Drug: GS-1101


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must meet the following criteria on screening examination to be eligible to participate in the study: Clinicopathological diagnosis of Waldenstrom's Macroglobulinemia and meeting criteria for treatment using consensus panel criteria from the Second International Workshop on Waldenstrom's macroglobulinemia (Owen 2003; Kyle 2003). Measurable disease, defined as presence of serum immunoglobulin M (IgM) with a minimum IgM level of > 2 times the upper limit of normal of each institution is required. Have received at least one prior therapy for WM. Age ≥18 years. ECOG performance status <2 (see Appendix A.). Participants must have normal organ and marrow function as defined below: Absolute neutrophil count > 1,000/mm3 Platelets > 50,000/mm3 Hemoglobin > 8 g/dL Total bilirubin ≤1.5 mg/dL or < 2 mg/dL if attributable to hepatic infiltration by neoplastic disease AST (SGOT) and ALT (SGPT) < 2.5 X institutional upper limit of normal Creatinine ≤ 2 mg/dL Not on any active therapy for other malignancies with the exception of topical therapies for basal cell or squamous cell cancers of the skin. Females of childbearing potential (FCBP) must agree to use two reliable forms of contraception simultaneously or have or will have complete abstinence from heterosexual intercourse during the following time periods related to this study: 1) while participating in the study; and 2) for at least 28 days after discontinuation from the study. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. FCBP must be referred to a qualified provider of contraceptive methods if needed. Able to adhere to the study visit schedule and other protocol requirements. Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Any serious medical condition, laboratory abnormality, uncontrolled intercurrent illness, or psychiatric illness/social condition that would prevent the participant from signing the informed consent form Concurrent use of any other anti-cancer agents or treatments or any other study agents Prior exposure to idelalisib Prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, ECG finding, or laboratory abnormality that, in the investigator's opinion, could affect the safety of the patient; alter the absorption, distribution, metabolism or excretion of Idelalisib; or impair the assessment of study results Grade > 2 toxicity (other than alopecia) continuing from prior anti-cancer therapy Known central nervous system lymphoma Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening New York Heart Association classification III or IV heart failure. Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction. Known history of Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), and/or Hepatitis C Virus (HCV) infection Lactating or pregnant women Inability to swallow capsules History of non-compliance to medical regimens Unwilling or unable to comply with the protocol

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GS-1101<br>After the screening procedures confirms eligibility to participate in the research study. Treatment will be administered on an outpatient basis. -- Idelalisib (GS-11-01) orally, predetermined dose twice daily per cycle for up to 6 cycles. After this initial 6 month period, for Cycles 7 and beyond, Idelalisib will be administered once a day until disease progression. | Drug: GS-1101<br>* Oral twice daily for 6 months followed by once daily until disease progression or unacceptable toxicity.<br>* Other names: CAL-101;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | ORR measured by decrease in serum IgM level by at least 25% from baseline. | Participants were followed for the duration of therapy, a median of one cycle, for up to 3 cycles. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Adverse Events | Assess the safety and tolerability of idelalisib | Participants were followed for the duration of therapy, a median of one cycle, for up to 3 cycles. | 
| Rate of Complete Response (CR) | CR measured by decrease in serum IgM levels to normal range, disappearnace of monoclonal protein by immunofixation, no evidence of bone marrow involvement, and resolution of any extramedullary disease by CT scan. | Participants were followed for the duration of therapy, a median of one cycle, for up to 3 cycles. | 
| Rate of Very Good Partial Response (VGPR) | VGPR measured by decrease in serum IgM levels of at least 90% from baseline. | Participants were followed for the duration of therapy, a median of one cycle, for up to 3 cycles. | 
| Rate of Partial Response (PR) | PR measured by decrease in serum IgM levels of between 25% and 50% from baseline. | Participants were followed for the duration of therapy, a median of one cycle, for up to 3 cycles. | 
| Rate of Minimal Response | Minimal response measured by decrease in serum IgM levels of between 25% and 50%. | Participants were followed for the duration of therapy, a median of one cycle, for up to 3 cycles. | 
| Rate of Stable Disease | Stable disease measured by serum IgM levels <25% reduced from baseline. | Participants were followed for the duration of therapy, a median of one cycle, for up to 3 cycles. | 
| Rate of Progressive Disease | Progressive disease measured by an 25% increase in serum IgM level with an absolute increase of at least 500mg/dL from the lowest attained IgM on therapy. | Participants were followed for the duration of therapy, a median of one cycle, for up to 3 cycles. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Waldenstrom's Macroglobulinemia