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

NCT ID: NCT02677324

Last Updated: 2022-05-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-09
• Study Completion Date: 2022-02-07

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.

Conditions

Waldenstrom Macroglobulinemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ABT199

ABT199 will be administered daily, with 28 consecutive days defined as a treatment cycle for a maximum for 26 cycles

Group Type: EXPERIMENTAL

ABT199

Intervention Type: DRUG

Oral BCL-2 antagonist

Interventions

ABT199

Oral BCL-2 antagonist

Intervention Type: DRUG

Other Intervention Names

Venetoclax

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: collaborator

Dana-Farber Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Jorge J. Castillo, MD

Jorge J. Castillo, MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jorge J Castillo, MD

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

City of Hope National Medical Center

Duarte, California, United States

Stanford University

Palo Alto, California, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Weill Cornell Medical College

New York, New York, United States

Countries

United States

References

Castillo JJ, Guijosa A, Allan JN, Siddiqi T, Advani RH, Flynn CA, Meid K, Budano N, Nguyen J, Ramirez-Gamero A, Tsakmaklis N, Hunter ZR, Patterson CJ, Treon SP, Sarosiek S. Long-term follow-up of venetoclax monotherapy in previously treated patients with Waldenstrom macroglobulinemia. Blood Adv. 2025 Oct 14;9(19):4842-4847. doi: 10.1182/bloodadvances.2025016890.

Reference Type: DERIVED

PMID: 40674749 (View on PubMed)

Castillo JJ, Allan JN, Siddiqi T, Advani RH, Meid K, Leventoff C, White TP, Flynn CA, Sarosiek S, Branagan AR, Demos MG, Guerrera ML, Kofides A, Liu X, Munshi M, Tsakmaklis N, Xu L, Yang G, Patterson CJ, Hunter ZR, Davids MS, Furman RR, Treon SP. Venetoclax in Previously Treated Waldenstrom Macroglobulinemia. J Clin Oncol. 2022 Jan 1;40(1):63-71. doi: 10.1200/JCO.21.01194. Epub 2021 Nov 18.

Reference Type: DERIVED

PMID: 34793256 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

A15-751

Identifier Type: OTHER

Identifier Source: secondary_id

15-491

Identifier Type: -

Identifier Source: org_study_id