Study of Ibrutinib in Patients With Symptomatic, Previously Untreated Waldenstrom's Macroglobulinemia, and Impact on Tumor Genomic Evolution Using Whole Genome Sequencing

NCT02604511 | Completed Phase 2 Results DMC

• 1 other identifier: 15-359
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 2

Brief Summary

This research study is studying a drug called ibrutinib as a possible treatment for untreated Waldenstrom's Macroglobulinemia (WM).

Conditions

Waldenstrom's Macroglobulinemia

Keywords

Waldenstrom's Macroglobulinemia

Outcome Measures

Primary Outcomes (2)

• Major Response Rate

  To asses the percentage of participants with a Partial Response (PR) (50% reduction or more in serum IgM) or better.

  4 years

• Best Overall Response Rate

  To asses the percentage of participants with an Minor Response (MR) (25% reduction or more in serum IgM) or better.

  4 years

Secondary Outcomes (1)

• Duration of Response

  6 years

Other Outcomes (3)

• Time to Response

  4 years

• Progression Free Survival

  6 years

• Overall Survival

  6 years

Study Arms (1)

Ibrutinib

EXPERIMENTAL

This is single arm, open label, Phase II, single center study designed to evaluate the safety and efficacy of ibrutinib in previously untreated WM patients. Treatment will be administered in 4-week cycles, and participants will receive treatment for up to 48 cycles. Treatment will be comprised of ibrutinib at 420 mg per day by oral administration.

Drug: Ibrutinib

Interventions

Ibrutinib DRUG

Also known as: Imbruvica, PCI-32765

Ibrutinib

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 (Kyle et al, 2003).
• Measurable disease, defined as presence of serum immunoglobulin M (IgM) with a minimum IgM level of ≥ 2 times the upper limit of normal is required.
• Age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (see Appendix A.).
• Participants must have normal organ and marrow function as defined below:
• Absolute neutrophil count ≥ 1,000/μL
• Platelets ≥ 50,000/μL
• Hemoglobin ≥ 8 g/dL
• Total bilirubin ≤ 2.0. mg/dL or \< 2.5 mg/dL if attributable to hepatic infiltration by neoplastic disease or Gilbert's syndrome.
• Aspartate aminotransferase (AST or SGOT) and Alanine aminotransferase (ALT or SGPT) ≤ 2.5 X institutional upper limit of normal
• Estimated Creatinine Clearance ≥30ml/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.

You may not qualify if:

• Prior systemic therapy for WM
• 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 treatments or any other investigational agents.
• Concomitant use of warfarin or other Vitamin K antagonists.
• Concomitant treatment with strong CYP3A4/5 inhibitor.
• Any condition, including the presence of laboratory abnormalities, which places the participant at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
• Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion could interfere with the absorption or metabolism of ibrutinib.
• Known Central nervous system (CNS) lymphoma.
• Concomitant use of medication known to cause QT prolongation.
• Currently active, clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification, or history of myocardial infarction, unstable angina or acute coronary syndrome within 6 months of screening.
• Malabsorption, 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), active infection with Hepatitis B Virus (HBV), and/or Hepatitis C Virus (HCV). Subjects who are positive for hepatitis B core antibody or hepatitis B surface antigen must have a negative polymerase chain reaction (PCR) result before enrollment. Those who are PCR positive will be excluded.
• Lactating or pregnant women.
• Inability to swallow capsules.
• History of non-compliance to medical regimens.

Sponsors & Collaborators

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

Study Sites (2)

Massacusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Related Publications (3)

• Guijosa A, Ramirez-Gamero A, Sarosiek S, Branagan AR, von Keudell G, Treon SP, Castillo JJ. Ibrutinib plus rituximab vs ibrutinib monotherapy in patients with Waldenstrom macroglobulinemia: a pooled analysis. Blood Adv. 2025 Sep 23;9(18):4705-4715. doi: 10.1182/bloodadvances.2025016536.

  PMID: 40674744 DERIVED

• Castillo JJ, Meid K, Gustine JN, Leventoff C, White T, Flynn CA, Sarosiek S, Demos MG, Guerrera ML, Kofides A, Liu X, Munshi M, Tsakmaklis N, Xu L, Yang G, Branagan AR, O'Donnell E, Raje N, Yee AJ, Patterson CJ, Hunter ZR, Treon SP. Long-term follow-up of ibrutinib monotherapy in treatment-naive patients with Waldenstrom macroglobulinemia. Leukemia. 2022 Feb;36(2):532-539. doi: 10.1038/s41375-021-01417-9. Epub 2021 Sep 16.

  PMID: 34531537 DERIVED

• Treon SP, Gustine J, Meid K, Yang G, Xu L, Liu X, Demos M, Kofides A, Tsakmaklis N, Chen JG, Munshi M, Chan G, Dubeau T, Raje N, Yee A, O'Donnell E, Hunter ZR, Castillo JJ. Ibrutinib Monotherapy in Symptomatic, Treatment-Naive Patients With Waldenstrom Macroglobulinemia. J Clin Oncol. 2018 Sep 20;36(27):2755-2761. doi: 10.1200/JCO.2018.78.6426. Epub 2018 Jul 25.

  PMID: 30044692 DERIVED

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia

Interventions

ibrutinib

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: Dr. Steven Treon
• Organization: Dana-Farber Cancer Institute

steven_treon@dfci.harvard.edu

617-632-2681

Study Officials

• Steven P Treon, MD, PhD

  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: Steven P. Treon, MD, PhD

Study Record Dates

• First Submitted: November 11, 2015
• First Posted: November 13, 2015
• Study Start: January 1, 2016
• Primary Completion: November 1, 2022
• Study Completion: November 1, 2022
• Last Updated: December 7, 2022
• Results First Posted: January 12, 2022

Record last verified: 2022-12

Locations

US (2)