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Waldenstrom Macroglobulinemia

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Immunoproliferative Disorders

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Amino Acids

Venetoclax

Ibrutinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

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.

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

IBRUTINIB

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

Jorge J Castillo, MD

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

* 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.
* The names of the study drugs involved in this study are:

  * Venetoclax
  * ibrutinib
* 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.
* 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.
* 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.

Ibrutinib + Venetoclax in Untreated WM

Phase II Study on the Combination of Ibrutinib and Venetoclax in Treatment naïve Patients With Waldenström Macroglobulinemia

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.

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

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.

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.

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.

Proportion of patients with minor response (MR) , partial response (PR), very good partial response (VGPR), or complete response (CR) to therapy.

Proportion of patients with a VGPR at 30 months from beginning therapy.

Time from treatment initiation until achievement of a minor response (reduction in serum IgM \>25%) or better.

Time from treatment initiation until partial response or better (\>50% reduction in serum IgM)

Time from initiation of therapy until disease progression (\>25% increase in serum IgM and 500 mg/dL absolute increase).

Time from initiation of therapy until death

Time from initiation of IVEN protocol therapy until initiation of new line of therapy.

AbbVie

Pharmacyclics LLC.

Dana-Farber Cancer Institute

Principal Investigator

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.

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

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Ibrutinib + Venetoclax in Untreated WM	NCT04273139	Waldenstrom Mac... MYD88 Gene Muta...	IBRUTINIB Venetoclax	18 Years -	Dana-Farber Cancer Institute
Ibrutinib + Venetoclax in Untreated WM	NCT04273139	Waldenstrom Mac... MYD88 Gene Muta...	IBRUTINIB Venetoclax	18 Years -	Dana-Farber Cancer Institute

Spots Global Cancer Trial Database for myd88 gene mutation