Safety issues from trials in CLL

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).

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.

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

Adverse events were collected from the time of screening until 30 days post treatment discontinuation, up to 16 weeks (median 4 weeks).

This study was terminated early due to safety concerns from the previously untreated CLL experience. All participants who remained on study at that time were permanently removed from protocol therapy. The median time on protocol therapy was 1 cycle