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

Waldenstrom's Macroglobulinemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT02439138
• Other study ID #: 15-040
• Secondary ID: ISR IN-US-313-16
• Status: Suspended
• Phase: Phase 2
• First received: April 29, 2015
• Last updated: March 21, 2016
• Start date: October 2015
• Est. completion date: May 2020

Study information

• Verified date: March 2016
• Source: Dana-Farber Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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).

Description:

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.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 30
• Est. completion date: May 2020
• Est. primary completion date: May 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Waldenstrom Macroglobulinemia
• Waldenstrom's Macroglobulinemia

Intervention

Drug:
• GS-1101

Locations

Country	Name	City	State
United States	Dana Farber Cancer Institute	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Dana-Farber Cancer Institute	Gilead Sciences

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate (ORR)	ORR measured by decrease in serum IgM levels	3 years	Yes
Secondary	Number of Adverse Events	Assess the safety and tolerability of idelalisib	2 years	Yes
Secondary	Rate of complete response (CR)	CR measured by decrease in serum IgM levels	3 years	Yes
Secondary	Rate of Very Good Partial Response (VGPR)	VGPR measured by decrease in serum IgM levels	3 years	Yes
Secondary	Rate of Partial Response (PR)	PR measured by decrease in serum IgM levels	3 years	Yes
Secondary	Rate of Minimal Response	Minimal response measured by decrease in serum IgM levels	3 years	Yes
Secondary	Rate of Stable Disease	Stable disease measured by serum IgM levels	3 years	Yes
Secondary	Rate of Progressive Disease	Progressive disease measured by serum IgM levels	4 years	Yes
Secondary	Progression free survival (PFS)	PFS measured in months from initiation of therapy	4 years	Yes
Secondary	Median Disease Free Survival (DFS)	DFS measured in months from achievement of CR	4 years	Yes
Secondary	Median time to progression (TTP)	TTP measured in months from initiation of therapy	2 Years	Yes
Secondary	Median Duration of Response (DOR)	DOR measured in months from achievement of CR	4 years	Yes
Secondary	Median Time to Next Therapy (TTNT)	TTNT measured in months from initiation of therapy	4 years	Yes
Secondary	MYD88 L265P burden in response to idelalisib in patients with WM	Measured by PCR	2 Years	Yes
Secondary	Association between depth of response and quantification of MYD88 L265P burden	Measured by PCR	2 Years	Yes
Secondary	Association between presence of CXCR4-WHIM-like mutations and response to idelalisib	Measured by Sanger Sequencing	2 Years	Yes