Waldenstrom's MacroglobulinemiaPhase 2NCT02604511
Study of Ibrutinib in Patients With Symptomatic, Previously Untreated Waldenstrom's Macroglobulinemia, and Impact on Tumor Genomic Evolution Using Whole Genome Sequencing
A Phase 2 study testing Ibrutinib in people with Waldenstrom's Macroglobulinemia, run by Dana-Farber Cancer Institute at 2 sites in United States.
Trial summary
This research study is studying a drug called ibrutinib as a possible treatment for untreated Waldenstrom's Macroglobulinemia (WM). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Waldenstrom's Macroglobulinemia
- What is being tested?
- Ibrutinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 2 sitesUnited States
- Study dates
- Jan 2016to 1 Nov 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Massacusetts General Hospital
Boston, Massachusetts, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
About this study
Official title: Phase II Study of Ibrutinib in Patients With Symptomatic, Previously Untreated Waldenstrom's Macroglobulinemia, and Impact on Tumor Genomic Evolution Using Whole Genome Sequencing
This research study is studying a drug called ibrutinib as a possible treatment for untreated Waldenstrom's Macroglobulinemia (WM).
Read the 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.
- Conditions
- Waldenstrom's Macroglobulinemia
- Being tested
- Ibrutinib
- Keywords
- Waldenstrom's Macroglobulinemia
- Medical subject headings
- Waldenstrom Macroglobulinemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IbrutinibDrug
Also called Imbruvica, PCI-32765
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Ibrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Major Response Rate
To asses the percentage of participants with a Partial Response (PR) (50% reduction or more in serum IgM) or better.
Measured: 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.
Measured: 4 years
Secondary outcomes (1)
Duration of Response
The amount of time between attainment of at least a minor response and disease progression.
Measured: 6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2015 (estimated)
- Study startJan 2016
- Primary completion1 Nov 2022
- Study completion1 Nov 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Waldenstrom's MacroglobulinemiaStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Pharmacyclics LLC.
- Responsible party
- Principal investigator, Steven Treon, MD, PhD, Dana-Farber Cancer Institute
- Investigators
- Steven P Treon, MD, PhD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02604511
- Sponsor's protocol ID
- 15-359
- Status last verified
- Dec 2022
- First submitted
- 11 Nov 2015
- Last updated
- 7 Dec 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Sun H, Sklavenitis-Pistofidis R, Liu S, Liu X, Tsakmaklis N, Hatcher JM, Guerrera ML, Kofides A, Ramirez-Gamero A, Peachey AL, Li S, Keskin DB, Chea V, Kim N, Lyu H, Lu W, Livak KJ, Meid K, Guijosa A, Flynn CA, Pizzarella D, Patterson CJ, Hao M, Yi S, Yuan W, Branagan AR, Wu CJ, Ghobrial IM, Qiu L, Sarosiek SR, Castillo JJ, Hunter ZR, Treon SP. Evolution of tumor subclones and T-cell dynamics underlie variable ibrutinib responses in Waldenstrom macroglobulinemia. Blood. 2026 May 14;147(20):2298-2314. doi: 10.1182/blood.2025032268.
PubMed 41671559Guijosa 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.
PubMed 40674744Castillo 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.
PubMed 34531537Treon 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.
PubMed 30044692
Study at a glance
From the registry record, last updated by the sponsor on 7 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Ibrutinib in Patients With Symptomatic, Previously Untreated Waldenstrom's Macroglobulinemia, and Impact on Tumor Genomic Evolution Using Whole Genome Sequencing
- ClinicalTrials.gov ID
- NCT02604511
- Acronym / sponsor ID
- 15-359
- Conditions
- Waldenstrom's Macroglobulinemia
- Keywords
- Waldenstrom's Macroglobulinemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- Pharmacyclics LLC.
- Study start
- Jan 2016 (actual)
- Primary completion
- 1 Nov 2022 (actual)
- Study completion
- 1 Nov 2022 (actual)
- First posted
- 13 Nov 2015 (estimated)
- Results
- Posted 12 Jan 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research study is studying a drug called ibrutinib as a possible treatment for untreated Waldenstrom's Macroglobulinemia (WM).
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ibrutinib | Experimental | Drug: IbrutinibThis 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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:
Key exclusion criteria (20 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IbrutinibAlso: Imbruvica, PCI-32765 | Drug | Ibrutinib |
Primary outcome
Major Response Rate
Time frame: 4 years
To asses the percentage of participants with a Partial Response (PR) (50% reduction or more in serum IgM) or better.
Best Overall Response Rate
Time frame: 4 years
To asses the percentage of participants with an Minor Response (MR) (25% reduction or more in serum IgM) or better.
1 secondary outcome
Duration of Response
Time frame: 6 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Dec 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41671559Sun H, Sklavenitis-Pistofidis R, Liu S, Liu X, Tsakmaklis N, Hatcher JM, Guerrera ML, Kofides A, Ramirez-Gamero A, Peachey AL, Li S, Keskin DB, Chea V, Kim N, Lyu H, Lu W, Livak KJ, Meid K, Guijosa A, Flynn CA, Pizzarella D, Patterson CJ, Hao M, Yi S, Yuan W, Branagan AR, Wu CJ, Ghobrial IM, Qiu L, Sarosiek SR, Castillo JJ, Hunter ZR, Treon SP. Evolution of tumor subclones and T-cell dynamics underlie variable ibrutinib responses in Waldenstrom macroglobulinemia. Blood. 2026 May 14;147(20):2298-2314. doi: 10.1182/blood.2025032268.
- Derived from this study: PubMed 40674744Guijosa 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.
- Derived from this study: PubMed 34531537Castillo 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.
- Derived from this study: PubMed 30044692Treon 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steven P Treon, MD, PhD principal investigator
Dana-Farber Cancer Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ibrutinib in people with Waldenstrom's Macroglobulinemia, run by Dana-Farber Cancer Institute at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Jan 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Major Response Rate (time frame: 4 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02604511, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Dec 2022.