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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.
 
ClinicalTrials.gov Identifier: NCT02677324
Recruitment Status : Active, not recruiting
First Posted : February 9, 2016
Results First Posted : May 11, 2021
Last Update Posted : May 11, 2021
Sponsor:
Collaborator:
AbbVie
Information provided by (Responsible Party):
Jorge J. Castillo, MD, Dana-Farber Cancer Institute

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.

Condition or disease Intervention/treatment Phase
Waldenstrom Macroglobulinemia Drug: ABT199 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 33 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of ABT-199 (GDC-199) In Patients With Relapsed Or Refractory Waldenström Macroglobulinemia
Actual Study Start Date : April 12, 2016
Actual Primary Completion Date : March 2020
Estimated Study Completion Date : March 2022


Arm Intervention/treatment
Experimental: ABT199
ABT199 will be administered daily, with 28 consecutive days defined as a treatment cycle for a maximum for 26 cycles
Drug: ABT199
Oral BCL-2 antagonist
Other Name: Venetoclax




Primary Outcome Measures :
  1. Overall Response Rate [ Time Frame: 2 years ]
    Overall Response Rate= Minor response (>25%-50% reduction in serum IgM from baseline) + Partial Response (>50-90% reduction in serum IgM from baseline) + Very Good Partial Response (>90% reduction in serum IgM from baseline) + Complete Response (resolution of all symptoms, normalization of serum IgM with disappearance of IgM paraprotein, resolution of any adenopathy or splenomegaly).


Secondary Outcome Measures :
  1. Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 [ Time Frame: 2 years ]
    Number of participants who experienced an adverse event while on ABT-199

  2. Number of Participants With Complete Response [ Time Frame: 2 years ]
    A complete response is defined as having resolution of WM related symptoms, normalization of serum IgM levels with complete disappearance of IgM paraprotein by immunofixation, and resolution of any adenopathy or splenomegaly.

  3. Number of Participants With Very Good Partial Response [ Time Frame: 2 years ]
    Very Good Partial Response (VGPR): is defined as ≥90% reduction in serum IgM levels, or normalization of serum IgM levels.

  4. Number of Participants With Partial Response [ Time Frame: 2 years ]
    Partial response (PR) is defined as achieving a ≥50% reduction in serum IgM levels.

  5. Number of Participants With Minor Response [ Time Frame: 2 years ]
    Minor Response (MR): A minor response (MR) is defined 25-49% reduction in serum IgM levels.

  6. Number of Participants With Stable Disease [ Time Frame: 2 years ]
    Stable disease is defined as having <25% increase in serum IgM levels and <25% reduction in serum IgM levels

  7. Progression Free Survival [ Time Frame: 4 years ]
    Amount of time following ABT-199 administration until >25% increase in serum IgM

  8. Overall Response Rate Among CXCR4 Mutated Participants [ Time Frame: 2 years ]
    Overall Response Rate for participants who tested positive for a CXCR4 mutation= Minor response (>25%-50% reduction in serum IgM from baseline) + Partial Response (>50-90% reduction in serum IgM from baseline) + Very Good Partial Response (>90% reduction in serum IgM from baseline) + Complete Response (resolution of all symptoms, normalization of serum IgM with disappearance of IgM paraprotein, resolution of any adenopathy or splenomegaly).

  9. Overall Response Rate Among Participants Without CXCR4 Mutations [ Time Frame: 2 years ]
    Overall Response Rate in participants who tested negative for a CXCR4 mutation= Minor response (>25%-50% reduction in serum IgM from baseline) + Partial Response (>50-90% reduction in serum IgM from baseline) + Very Good Partial Response (>90% reduction in serum IgM from baseline) + Complete Response (resolution of all symptoms, normalization of serum IgM with disappearance of IgM paraprotein, resolution of any adenopathy or splenomegaly).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02677324


Locations
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United States, California
City of Hope National Medical Center
Duarte, California, United States, 91010
Stanford University
Palo Alto, California, United States, 94304
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, New York
Weill Cornell Medical College
New York, New York, United States, 10065
Sponsors and Collaborators
Dana-Farber Cancer Institute
AbbVie
Investigators
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Principal Investigator: Jorge J Castillo, MD Dana-Farber Cancer Institute
  Study Documents (Full-Text)

Documents provided by Jorge J. Castillo, MD, Dana-Farber Cancer Institute:
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Responsible Party: Jorge J. Castillo, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT02677324    
Other Study ID Numbers: 15-491
A15-751 ( Other Identifier: AbbVie Inc )
First Posted: February 9, 2016    Key Record Dates
Results First Posted: May 11, 2021
Last Update Posted: May 11, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Jorge J. Castillo, MD, Dana-Farber Cancer Institute:
Waldenstrom Macroglobulinemia
WM
Additional relevant MeSH terms:
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Waldenstrom Macroglobulinemia
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Venetoclax
Antineoplastic Agents