February 14, 2020
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February 17, 2020
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February 28, 2024
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April 23, 2024
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April 23, 2024
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July 9, 2020
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June 6, 2022 (Final data collection date for primary outcome measure)
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Number of Participants With Very Good Partial Response Within 24 Cycles of Therapy [ Time Frame: 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. ] Proportion of patients with VGPR to therapy within 24 cycles of therapy initiation. (VGPR is >90% reduction in serum IgM from baseline)
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Rate of Very Good Partial Response (VGPR) [ Time Frame: 24 Months ] Proportion of patients with VGPR to therapy. (VGPR is >90% reduction in serum IgM from baseline)
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- Number of Participants With Complete Response (CR) After 6 Cycles [ Time Frame: 6 Cycles (28 day cycle) ]
Proportion of patients with a complete response after 6 cycles of therapy. A complete response (CR) is defined as having resolution of WM related symptoms, normalization of serum IgM levels with complete disappearance of IgM paraprotein by immunofixation, and resolution of any adenopathy or splenomegaly.
- Number of Participants With Complete Response (CR) After 12 Cycles [ Time Frame: 12 Cycles (28 day cycle) ]
Proportion of patients with a complete response after 12 cycles of therapy. A complete response (CR) is defined as having resolution of WM related symptoms, normalization of serum IgM levels with complete disappearance of IgM paraprotein by immunofixation, and resolution of any adenopathy or splenomegaly.
- Number of Participants With Complete Response (CR) After 24 Cycles [ Time Frame: 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. ]
Proportion of patients with a complete response after 24 cycles of therapy. A complete response (CR) is defined as having resolution of WM related symptoms, normalization of serum IgM levels with complete disappearance of IgM paraprotein by immunofixation, and resolution of any adenopathy or splenomegaly.
- Overall Response [ Time Frame: 72 months ]
Proportion of patients with minor response (MR) , partial response (PR), very good partial response (VGPR), or complete response (CR) to therapy.
- Rate of VGPR at 30 Months [ Time Frame: 30 Months ]
Proportion of patients with a VGPR at 30 months from beginning therapy.
- Median Time to Response [ Time Frame: 24 months ]
Time from treatment initiation until achievement of a minor response (reduction in serum IgM >25%) or better.
- Median Time to Major Response [ Time Frame: 24 months ]
Time from treatment initiation until partial response or better (>50% reduction in serum IgM)
- Progression Free Survival (PFS) at 24 Months [ Time Frame: 24 months ]
Time from initiation of therapy until disease progression (>25% increase in serum IgM and 500 mg/dL absolute increase).
- Progression Free Survival (PFS) at 36 Months [ Time Frame: 36 Months ]
Time from initiation of therapy until disease progression (>25% increase in serum IgM and 500 mg/dL absolute increase).
- Progression Free Survival (PFS) at 48 Months [ Time Frame: 48 Months ]
Time from initiation of therapy until disease progression (>25% increase in serum IgM and 500 mg/dL absolute increase).
- Progression Free Survival (PFS) at 60 Months [ Time Frame: 60 Months ]
Time from initiation of therapy until disease progression (>25% increase in serum IgM and 500 mg/dL absolute increase).
- Overall Survival [ Time Frame: 72 months ]
Time from initiation of therapy until death
- Time to Next Treatment [ Time Frame: 72 months ]
Time from initiation of IVEN protocol therapy until initiation of new line of therapy.
- Number of Participants With Treatment Related Adverse Events as Assessed (CTCAE) Version 5.0 [ Time Frame: 6 Months ]
CTCAE version 5.0
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- Rate of Complete Response (CR) 6 Cycles [ Time Frame: 6 Cycles (28 day cycle) ]
Proportion of patients with a complete response after 6 cycles of therapy
- Rate of Complete Response (CR) 12 Cycles [ Time Frame: 12 Cycles (28 day cycle) ]
Proportion of patients with a complete response after 12 cycles of therapy
- Rate of Complete Response (CR) 24 Cycles [ Time Frame: 24 Cycles (28 day cycle) ]
Proportion of patients with a complete response after 24 cycles of therapy
- Overall Response 24 Cycles [ Time Frame: 24 Cycles (28 day cycle) ]
Proportion of patients with minor response (MR) , partial response (PR), very good partial response (VGPR), or complete response (CR) to therapy.
- Rate of VGPR at 30 months [ Time Frame: 30 Months ]
Proportion of patients with a VGPR at 30 months from beginning therapy.
- Median time to response [ Time Frame: 12 Months ]
Time from treatment initiation until first response
- Median time to major response [ Time Frame: 12 Months ]
Time from treatment initiation until partial response or better (>50% reduction in serum IgM)
- median time to VGPR [ Time Frame: 12 Months ]
Time from treatment initiation until very good partial response (>90% reduction in serum IgM)
- Progression Free Survival (PFS) [ Time Frame: 24 Months ]
Time from initiation of therapy until disease progression (>25% increase in serum IgM and 500 mg/dL absolute increase).
- Progression Free Survival (PFS) [ Time Frame: 36 Months ]
Time from initiation of therapy until disease progression (>25% increase in serum IgM and 500 mg/dL absolute increase).
- Progression Free Survival (PFS) [ Time Frame: 48 Months ]
Time from initiation of therapy until disease progression (>25% increase in serum IgM and 500 mg/dL absolute increase).
- Progression Free Survival (PFS) [ Time Frame: 60 Months ]
Time from initiation of therapy until disease progression (>25% increase in serum IgM and 500 mg/dL absolute increase).
- Overall survival [ Time Frame: duration of time from start of treatment to time of death or last follow-up up to 72 months ]
Time from initiation of therapy until death
- Time to next treatment [ Time Frame: 24 Months ]
Time from initiation of IVEN protocol therapy until initiation of new line of therapy.
- impact of IVEN in the participants' QOL [ Time Frame: 24 Months ]
EORTC QLQ-C30 (version 3)
- Number of participants with Treatment Related Adverse Events as Assessed (CTCAE) version 5.0 [ Time Frame: 6 Months ]
CTCAE version 5.0
- Impact ofCXCR4 mutations on overall response [ Time Frame: 12 Months ]
Comparison of response rates between participants with CXCR4 mutations and without CXCR4 mutations
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Not Provided
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Not Provided
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Ibrutinib + Venetoclax in Untreated WM
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Phase II Study on the Combination of Ibrutinib and Venetoclax in Treatment naïve Patients With Waldenström Macroglobulinemia
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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:
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- This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.
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The names of the study drugs involved in this study are:
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The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.
- Participants will be on the research study for up to 2 years on combined venetoclax and ibrutinib and 4 years of follow-up .
- It is expected that about 50 people will take part in this research study.
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The U.S. Food and Drug Administration (FDA) has not approved venetoclax for your specific disease but it has been approved for other uses.
-- Venetoclax is a targeted therapy that blocks BCL-2, a protein that is important for the survival of WM cells. Laboratory studies and early clinical data have shown that the investigational new agent, venetoclax, may kill cancer cells and may cause tumors to shrink.
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The U.S. Food and Drug Administration (FDA) has approved ibrutinib as a treatment option for this disease.
--Ibrutinib is a targeted therapy that blocks BTK. It has been FDA approved in chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), chronic graft vs. host disease (cGVHD), and Waldenstrom's macroglobulinemia (WM). It is also used in research studies in participants with recurrent B-cell lymphoma), diffuse large B-cell lymphoma (DLBCL), and prolymphocytic leukemia. In a study of ibrutinib in relapsed/refractory WM patients, response rates were high and the treatment was well tolerated.
- The U.S. Food and Drug Administration (FDA) has not approved the combination of ibrutinib and venetoclax as a treatment for any disease.
- The U.S. Food and Drug Administration (FDA) has not approved the MYD88 test. This test is investigational.
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Interventional
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Phase 2
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Allocation: N/A Intervention Model: Sequential Assignment Masking: None (Open Label) Primary Purpose: Treatment
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- Waldenstrom Macroglobulinemia
- MYD88 Gene Mutation
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- Drug: IBRUTINIB
Ibrutinib Cycle 1-24 will be administered at a predetermined dose, once daily for 28 days
Other Name: Imbruvica
- Drug: Venetoclax
Venetoclax Cycle 2-24 will be administered daily for 28 days. Predetermined dosage ramp up schedule during cycle 2.
Other Name: Venclexta
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Experimental: Ibrutinib and Venetoclax
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.
Interventions:
- Drug: IBRUTINIB
- Drug: Venetoclax
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Not Provided
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Active, not recruiting
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45
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50
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February 1, 2028
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June 6, 2022 (Final data collection date for primary outcome measure)
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Inclusion Criteria:
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Sexes Eligible for Study: |
All |
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18 Years and older (Adult, Older Adult)
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No
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Contact information is only displayed when the study is recruiting subjects
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United States
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NCT04273139
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19-651
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Yes
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Studies a U.S. FDA-regulated Drug Product: |
Yes |
Studies a U.S. FDA-regulated Device Product: |
No |
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Plan to Share IPD: |
Yes |
Plan Description: |
The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research. |
Supporting Materials: |
Study Protocol |
Supporting Materials: |
Statistical Analysis Plan (SAP) |
Supporting Materials: |
Informed Consent Form (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 |
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Jorge J. Castillo, MD, Dana-Farber Cancer Institute
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Same as current
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Dana-Farber Cancer Institute
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Same as current
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- AbbVie
- Pharmacyclics LLC.
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Principal Investigator: |
Jorge J Castillo, MD |
Dana-Farber Cancer Institute |
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Dana-Farber Cancer Institute
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March 2024
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