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Study of ABT-199 (GDC-199) In Patients With Relapsed Or Refractory Waldenström Macroglobulinemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02677324
Recruitment Status : Active, not recruiting
First Posted : February 9, 2016
Last Update Posted : May 2, 2019
Information provided by (Responsible Party):
Jorge J. Castillo, MD, Dana-Farber Cancer Institute

Tracking Information
First Submitted Date  ICMJE January 14, 2016
First Posted Date  ICMJE February 9, 2016
Last Update Posted Date May 2, 2019
Actual Study Start Date  ICMJE April 12, 2016
Estimated Primary Completion Date February 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 4, 2016)
The Overall Response Rate (ORR) Of ABT-199 In Symptomatic WM Patients [ Time Frame: 2 years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02677324 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 4, 2016)
  • Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 2 years ]
  • Rate Of Complete Response (CR), [ Time Frame: 2 years ]
  • Rate Of Very Good Partial Response (VGPR) [ Time Frame: 2 years ]
  • Rate Of Partial Response (PR) [ Time Frame: 2 years ]
  • Rate Of Minimal Response (MR) [ Time Frame: 2 years ]
  • Rate Of Stable Disease (SD) [ Time Frame: 2 years ]
  • Rate Of Progressive Disease (PD) [ Time Frame: 2 years ]
  • To evaluate the best response to ABT-199 by MYD88 and CXCR4 status [ Time Frame: 2 years ]
    MYD88 and CXCR4 mutational status will be determined at baseline by bone marrow biopsy
  • The 2-Year Progression-Free Survival (PFS) [ Time Frame: 2 years ]
  • The 4-Year Progression-Free Survival (PFS) [ Time Frame: 4 years ]
  • The 2-Year Overall Survival (OS) [ Time Frame: 2 years ]
  • The 4-Year Overall Survival (OS) [ Time Frame: 4 years ]
  • Median Duration Of Response [ Time Frame: 2 years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Study of ABT-199 (GDC-199) In Patients With Relapsed Or Refractory Waldenström Macroglobulinemia
Official Title  ICMJE Phase II Study of ABT-199 (GDC-199) In Patients With Relapsed Or Refractory Waldenström Macroglobulinemia
Brief Summary This research study is studying a targeted therapy as a possible treatment for relapsed or refractory Waldenstrom's Macroglobulinemia (WM). This study is using the study intervention ABT-199.
Detailed Description

This research study is a Phase II clinical trial. ABT-199 is a pill that blocks BCL-2, a protein that is important for the survival of WM cells.

The purpose of this research study is to evaluate how well the study drug works and the safety of ABT-199 as a single agent in participants with WM that has come back or has shown no response to previous treatment.

The FDA (the U.S. Food and Drug Administration) has not approved ABT-199 as a treatment for any disease.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Waldenstrom Macroglobulinemia
Intervention  ICMJE Drug: ABT199
Oral BCL-2 antagonist
Other Name: Venetoclax
Study Arms  ICMJE Experimental: ABT199
ABT199 will be administered daily, with 28 consecutive days defined as a treatment cycle for a maximum for 26 cycles
Intervention: Drug: ABT199
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: February 26, 2018)
Original Estimated Enrollment  ICMJE
 (submitted: February 4, 2016)
Estimated Study Completion Date  ICMJE February 2022
Estimated Primary Completion Date February 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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 (growth factors cannot be given prophylactically to establish eligibility) 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) < 2.5X the institutional upper limit of normal
    • Creatinine clearance ≥50 ml/min
  • 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 ABT-199 or BCL2 inhibitors.
  • 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, including symptomatic hyperviscosity; alter the absorption, distribution, metabolism or excretion of ABT-199; or impair the assessment of study results.
  • Grade > 2 toxicity (other than alopecia) continuing from prior anti-cancer therapy.
  • Known CNS 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 tablets.
  • History of non-compliance to medical regimens.
  • Unwilling or unable to comply with the protocol.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT02677324
Other Study ID Numbers  ICMJE 15-491
A15-751 ( Other Identifier: AbbVie Inc )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Jorge J. Castillo, MD, Dana-Farber Cancer Institute
Study Sponsor  ICMJE Dana-Farber Cancer Institute
Collaborators  ICMJE AbbVie
Investigators  ICMJE
Principal Investigator: Jorge J Castillo, MD Dana-Farber Cancer Institute
PRS Account Dana-Farber Cancer Institute
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP