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

NCT02439138 | Terminated Phase 2 Results DMC

• 2 other identifiers: 15-040ISR IN-US-313-1609
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Waldenstrom's Macroglobulinemia

Keywords

Waldenstrom's Macroglobulinemia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Percentage of Participants With Adverse Events

  Participants were followed for the duration of therapy, a median of one cycle, for up to 3 cycles.

• Rate of Complete Response (CR)

  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)

  Participants were followed for the duration of therapy, a median of one cycle, for up to 3 cycles.

• Rate of Partial Response (PR)

  Participants were followed for the duration of therapy, a median of one cycle, for up to 3 cycles.

• Rate of Minimal Response

  Participants were followed for the duration of therapy, a median of one cycle, for up to 3 cycles.

Study Arms (1)

GS-1101

EXPERIMENTAL

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

Interventions

GS-1101 DRUG

Oral twice daily for 6 months followed by once daily until disease progression or unacceptable toxicity.

Also known as: Idealisib, Zydelig, CAL-101

GS-1101

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Gilead Sciences: collaborator

Study Sites (1)

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia

Interventions

idelalisib

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Limitations and Caveats

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

Results Point of Contact

• Title: Jorge J. Castillo
• Organization: Dana-Farber Cancer Institute

jorgej_castillo@dfci.harvard.edu

617-632-6045

Study Officials

• Jorge J. Castillo, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 29, 2015
• First Posted: May 8, 2015
• Study Start: October 1, 2015
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: January 11, 2017
• Results First Posted: January 11, 2017

Record last verified: 2016-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)