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

NCT02677324 | Completed Phase 2 Results DMC

• 2 other identifiers: 15-491A15-751
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 4

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.

Conditions

Waldenstrom Macroglobulinemia

Keywords

Waldenstrom Macroglobulinemia; WM

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  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).

  2 years

Secondary Outcomes (9)

• Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0

  2 years

• Number of Participants With Complete Response

  2 years

• Number of Participants With Very Good Partial Response

  2 years

• Number of Participants With Partial Response

  2 years

• Number of Participants With Minor Response

  2 years

Study Arms (1)

ABT199

EXPERIMENTAL

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

Drug: ABT199

Interventions

ABT199 DRUG

Oral BCL-2 antagonist

Also known as: Venetoclax

ABT199

Eligibility Criteria

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

You may qualify if:

• 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.

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 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.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• AbbVie: collaborator

Study Sites (4)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Weill Cornell Medical College

New York, New York, 10065, United States

Location

Related Publications (2)

• 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.

  PMID: 40674749 DERIVED

• 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.

  PMID: 34793256 DERIVED

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia

Interventions

venetoclax

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

Results Point of Contact

• Title: Jorge J. Castillo
• Organization: DFCI

jorgej_Castillo@dfci.harvard.edu

617-632-2681

Study Officials

• Jorge J Castillo, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: Jorge J. Castillo, MD

Study Record Dates

• First Submitted: January 14, 2016
• First Posted: February 9, 2016
• Study Start: May 9, 2016
• Primary Completion: February 14, 2020
• Study Completion: February 7, 2022
• Last Updated: May 11, 2022
• Results First Posted: May 11, 2021

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)