- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02604511
Study of Ibrutinib in Patients With Symptomatic, Previously Untreated Waldenstrom's Macroglobulinemia, and Impact on Tumor Genomic Evolution Using Whole Genome Sequencing
Phase II Study of Ibrutinib in Patients With Symptomatic, Previously Untreated Waldenstrom's Macroglobulinemia, and Impact on Tumor Genomic Evolution Using Whole Genome Sequencing
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.
The FDA (the U.S. Food and Drug Administration) has approved ibrutinib as a form of treatment for the patient specific disease.
Ibrutinib has been under investigation in research studies in participants with recurrent B-cell lymphoma, chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), and prolymphocytic leukemia, and WM. In a study of ibrutinib in relapsed/refractory WM patients, response rates were high and the treatment was well tolerated.
The prior studies suggest that ibrutinib may be a useful treatment strategy for untreated WM patients. This study will test the safety and efficacy of ibrutinib as an option for untreated WM patients. The study will also conduct genomic sequencing of malignant WM cells before the start of treatment, and 6, 12, 24, 36 and 48 months afterwards. Genomic sequencing is the analysis of the entire DNA structure from tumor and normal cells. The purpose of this sequencing is to study which genetic changes effect how ibrutinib works. The results of these studies could also help in better understanding the course of WM disease, and be applicable to the development of other effective drug treatments.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Massachusetts
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Boston, Massachusetts, United States, 02215
- Dana-Farber Cancer Institute
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Boston, Massachusetts, United States, 02114
- Massacusetts General Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 (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.
- Both men and women of all races and ethnic groups are eligible for this trial.
Exclusion Criteria:
- 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.
- Unwilling or unable to comply with the protocol.
- Major surgery within 4 weeks of first dose of study drug.
- No active infections requiring systemic therapy.
- Known bleeding disorders with the exception of acquired Von Willebrand Disorder suspected on the basis of WM.
- History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Ibrutinib
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.
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Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Major Response Rate
Time Frame: 4 years
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To asses the percentage of participants with a Partial Response (PR) (50% reduction or more in serum IgM) or better.
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4 years
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Best Overall Response Rate
Time Frame: 4 years
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To asses the percentage of participants with an Minor Response (MR) (25% reduction or more in serum IgM) or better.
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4 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Duration of Response
Time Frame: 6 years
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The amount of time between attainment of at least a minor response and disease progression.
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6 years
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Time to Response
Time Frame: 4 years
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The amount of time between starting treatment and attaining at least a minor response to therapy
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4 years
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Progression Free Survival
Time Frame: 6 years
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The number of participants who have not experienced disease progression 6 years after therapy initiation
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6 years
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Overall Survival
Time Frame: 6 years
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The number of participants who are still living 6 years after initiation of ibrutinib
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6 years
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Steven P Treon, MD, PhD, Dana-Farber Cancer Institute
Publications and helpful links
General Publications
- 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.
- 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Neoplasms, Plasma Cell
- Waldenstrom Macroglobulinemia
Other Study ID Numbers
- 15-359
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Waldenstrom's Macroglobulinemia
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Weill Medical College of Cornell UniversityMayo Clinic; Janssen Scientific Affairs, LLCTerminatedWaldenstrom Macroglobulinemia | Waldenstrom's Macroglobulinemia Recurrent | Waldenstrom's Macroglobulinemia Refractory | Waldenstrom's Disease | Waldenström; Hypergammaglobulinemia | Waldenstrom's Macroglobulinemia of Lymph Nodes | Waldenstrom's Macroglobulinaemia, Without Mention of RemissionUnited States
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BeiGeneRecruitingWaldenstrom Macroglobulinemia | Waldenstrom's Macroglobulinemia Recurrent | Waldenstrom's Macroglobulinemia RefractoryUnited States, Australia, China, Spain, United Kingdom
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Beijing InnoCare Pharma Tech Co., Ltd.CompletedWaldenstrom's Macroglobulinemia Recurrent | Waldenstrom's Macroglobulinemia RefractoryChina
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Dana-Farber Cancer InstituteNovartis; Millennium Pharmaceuticals, Inc.TerminatedWaldenstrom's MacroglobulinemiaUnited States
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Idera Pharmaceuticals, Inc.TerminatedWaldenstrom's MacroglobulinemiaUnited States
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Dana-Farber Cancer InstituteAmgenCompletedWaldenstrom's MacroglobulinemiaUnited States
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Dana-Farber Cancer InstituteBeth Israel Deaconess Medical Center; Genentech, Inc.; Brigham and Women's Hospital and other collaboratorsTerminatedWaldenstrom's MacroglobulinemiaUnited States
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Dana-Farber Cancer InstituteBeth Israel Deaconess Medical CenterCompleted
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Dana-Farber Cancer InstituteBristol-Myers SquibbActive, not recruitingWaldenstrom's MacroglobulinemiaUnited States
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Fondazione Italiana Linfomi ONLUSCompletedWaldenstrom's MacroglobulinemiaItaly
Clinical Trials on Ibrutinib
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Christian BuskeAmgen; Janssen, LPRecruitingWaldenstrom MacroglobulinemiaAustria, Germany, Greece
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TG Therapeutics, Inc.CompletedMantle Cell Lymphoma | Chronic Lymphocytic LeukemiaUnited States
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Johnson & Johnson Private LimitedCompletedLymphoma, Mantle-Cell | Leukemia, Lymphocytic, Chronic, B-CellIndia
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Janssen Research & Development, LLCCompleted
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Janssen Research & Development, LLCCompleted
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Oncternal Therapeutics, IncUniversity of California, San Diego; Pharmacyclics LLC.; California Institute...Active, not recruitingMantle Cell Lymphoma | Marginal Zone Lymphoma | B-cell Chronic Lymphocytic Leukemia | Small Lymphocytic LymphomaUnited States
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The Lymphoma Academic Research OrganisationJanssen Pharmaceutica N.V., BelgiumTerminatedB-cell LymphomaFrance, Belgium
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Pharmacyclics Switzerland GmbHJanssen Biotech, Inc., including Johnson & JohnsonEnrolling by invitationLymphoma, B-Cell | Lymphoma, Non-Hodgkin | Solid Tumor | Leukemia, B-cell | Graft Vs Host DiseaseUnited States, Spain, Taiwan, United Kingdom, Australia, Italy, Russian Federation, Canada, New Zealand, Korea, Republic of, France, Turkey, Czechia, Hungary, Poland, Sweden
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Janssen-Cilag Ltd.CompletedLymphoma, Mantle-Cell | Leukemia, Lymphocytic, Chronic, B-CellFrance
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The Lymphoma Academic Research OrganisationCompletedIntraocular Lymphoma | Primary Central Nervous LymphomaFrance