Ibrutinib + Venetoclax in Untreated WM

NCT04273139 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: 19-651
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 2

Brief Summary

This study evaluates the safety and efficacy of Ibrutinib combined with Venetoclax (IVEN) in the treatment of adults diagnosed with Waldenstrom's macroglobulinemia (WM) cancer with a specific MYD88 gene mutation. This research study involves an experimental drug combination of targeted therapies. The names of the study drugs involved in this study are:

• Venetoclax
• ibrutinib

Conditions

Waldenstrom Macroglobulinemia; MYD88 Gene Mutation

Keywords

Waldenstrom Macroglobulinemia; ibrutinib; venetoclax

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Very Good Partial Response Within 24 Cycles of Therapy

  Proportion of patients with VGPR to therapy within 24 cycles of therapy initiation. (VGPR is \>90% reduction in serum IgM from baseline)

  The primary objective of VGPR within 24 cycles of therapy was assessed starting at Cycle 3 Day 1 through the End of Treatment visit, range of 2 to 21 months after the initiation of therapy.

Secondary Outcomes (14)

• Number of Participants With Complete Response (CR) After 6 Cycles

  6 Cycles (28 day cycle)

• Number of Participants With Complete Response (CR) After 12 Cycles

  12 Cycles (28 day cycle)

• Number of Participants With Complete Response (CR) After 24 Cycles

  Complete response to therapy was assessed starting at Cycle 3 Day 1 through the End of Treatment visit, range of 2 to 21 months after the initiation of therapy.

• Overall Response

  72 months

• Rate of VGPR at 30 Months

  30 Months

Study Arms (1)

Ibrutinib and Venetoclax

EXPERIMENTAL

The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits. * Ibrutinib will be administered at a predetermined dose, once daily for 28 days * TLS Prophylaxis (Treatment to reduce risk of tumor lysis syndrome) prior to first dose of venetoclax (and for at least the first 2 weeks of treatment) * Venetoclax Cycle 2-24. PO daily, predetermined dosage ramp up during cycle 2.

Drug: IBRUTINIB; Drug: Venetoclax

Interventions

IBRUTINIB DRUG

Ibrutinib Cycle 1-24 will be administered at a predetermined dose, once daily for 28 days

Also known as: Imbruvica

Ibrutinib and Venetoclax

Venetoclax DRUG

Venetoclax Cycle 2-24 will be administered daily for 28 days. Predetermined dosage ramp up schedule during cycle 2.

Also known as: Venclexta

Ibrutinib and Venetoclax

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. Screening evaluations including consent, physical exam, and laboratory assessments will be done within 30 days prior to Cycle 1 Day 1. Bone marrow biopsy \& aspirate, and CT C/A/P will be done within 90 days prior to Cycle 1 Day 1.
• Clinicopathological diagnosis of Waldenström macroglobulinemia \[28\].
• Known tumor expression of mutated MYD88 performed by a CLIA certified laboratory.
• Symptomatic disease meeting criteria for treatment using consensus panel criteria from the Second International Workshop on Waldenström macroglobulinemia \[29\].
• Participants with symptomatic hyperviscosity (e.g. nosebleeds, headaches, blurred vision) must undergo plasmapheresis prior to treatment initiation.
• Age ≥ 18 years
• ECOG performance status ≤2 (see Appendix A)
• Measurable disease, defined as presence of serum immunoglobin M (IgM) with a minimum IgM level of \>2 times the upper limit of normal of each institution is required
• At the time of screening, participants must have acceptable organ and marrow function as defined below:
• Absolute neutrophil count ≥500/uL (no growth factor permitted)
• Platelets ≥50,000/uL (no platelet transfusions permitted)
• Hemoglobin ≥ 7 g/dL (transfusions permitted)
• Total bilirubin \< 1.5 x institutional ULN
• AST(SGOT)/ALT(SGPT) ≤2.5 × institutional ULN
• Estimated GFR ≥30 mL/min

You may not qualify if:

• Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study:
• Participants who have one or more prior systemic therapies for WM.
• Participants who are receiving any other investigational agents.
• Participants with known CNS lymphoma.
• Participants with known history of Human Immunodeficiency Virus (HIV), chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring active treatment. Note: Participants with serologic evidence of prior vaccination to HBV (i.e., HBs Ag-, and anti-HBs+ and anti-HBC-) and positive anti-HBc from IVIG may participate.
• Concurrent administration of medications or foods that are moderate or strong inhibitors or inducers of CYP3A within 7 days prior to first dose of study drug.
• Participants with chronic liver disease and hepatic impairment meeting Child-Pugh class C (Appendix B).
• Concurrent administration of warfarin.
• Concurrent systemic immunosuppressant therapy within 21 days of the first dose of study drug.
• Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug.
• Recent infection requiring systemic treatment that was completed ≤ 14 days before the first dose of the study drug.
• Known bleeding disorders (e.g., congenital von Willebrand's disease or hemophilia)
• History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
• Major surgery within 4 weeks of first dose of study drug.
• Malabsorption syndrome or other condition that precludes enteral route of administration.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• AbbVie: collaborator
• Pharmacyclics LLC.: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02214, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• Castillo JJ, Branagan AR, Sermer D, Flynn CA, Meid K, Little M, Stockman K, White T, Canning A, Guerrera ML, Kofides A, Liu S, Liu X, Richardson K, Tsakmaklis N, Patterson CJ, Hunter ZR, Treon SP, Sarosiek S. Ibrutinib and venetoclax as primary therapy in symptomatic, treatment-naive Waldenstrom macroglobulinemia. Blood. 2024 Feb 15;143(7):582-591. doi: 10.1182/blood.2023022420.

  PMID: 37971194 DERIVED

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia

Interventions

ibrutinib; 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, Md
• Organization: Dana-Farber Cancer Institute

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: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: February 14, 2020
• First Posted: February 17, 2020
• Study Start: July 9, 2020
• Primary Completion: June 6, 2022
• Study Completion (Estimated): February 1, 2028
• Last Updated: July 30, 2025
• Results First Posted: April 23, 2024

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (2)