Brief Title
Ibrutinib + Venetoclax in Untreated WM
Official Title
Phase II Study on the Combination of Ibrutinib and Venetoclax in Treatment naïve Patients With Waldenström Macroglobulinemia
Brief Summary
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
Detailed Description
- 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.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Rate of Very Good Partial Response (VGPR)
Secondary Outcome
Rate of Complete Response (CR) 6 Cycles
Condition
Waldenstrom Macroglobulinemia
Intervention
IBRUTINIB
Study Arms / Comparison Groups
Ibrutinib and Venetoclax (3 dose ramp up)
Description: The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits. First 12 participants 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
50
Start Date
June 24, 2020
Completion Date
June 1, 2029
Primary Completion Date
June 1, 2023
Eligibility Criteria
Inclusion Criteria:
- Participants must meet the following criteria on screening examination to be eligible
to participate. Screening evaluations including consent, physical exam, and laboratory
assessments will be done within 30 days prior to Cycle 1 Day 1. Bone marrow biopsy &
aspirate, and CT C/A/P will be done within 90 days prior to Cycle 1 Day 1.
- Clinicopathological diagnosis of Waldenström macroglobulinemia [28].
- Known tumor expression of mutated MYD88 performed by a CLIA certified laboratory.
- Symptomatic disease meeting criteria for treatment using consensus panel criteria from
the Second International Workshop on Waldenström macroglobulinemia [29].
- Participants with symptomatic hyperviscosity (e.g. nosebleeds, headaches, blurred
vision) must undergo plasmapheresis prior to treatment initiation.
- Age ≥ 18 years
- ECOG performance status ≤2 (see Appendix A)
- Measurable disease, defined as presence of serum immunoglobin M (IgM) with a minimum
IgM level of >2 times the upper limit of normal of each institution is required
- At the time of screening, participants must have acceptable organ and marrow function
as defined below:
- Absolute neutrophil count ≥500/uL (no growth factor permitted)
- Platelets ≥50,000/uL (no platelet transfusions permitted)
- Hemoglobin ≥ 7 g/dL (transfusions permitted)
- Total bilirubin < 1.5 x institutional ULN
- AST(SGOT)/ALT(SGPT) ≤2.5 × institutional ULN
- Estimated GFR ≥30 mL/min
- Females of childbearing potential (FCBP) must use one reliable form of contraception
or 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 90 days after discontinuation from the study. FCBP must be referred to a
qualified provider of contraceptive methods if needed. FCBP must have a negative serum
pregnancy test at screening.
- Men must agree to use a latex condom during treatment and for up to 90 days after the
last dose of ibrutinib or venetoclax during sexual contact with a FCBP
- Ability to understand and the willingness to sign a written informed consent document.
- Exclusion Criteria
- Participants who exhibit any of the following conditions at screening will not be
eligible for admission into the study:
- Participants who have one or more prior systemic therapies for WM.
- Participants who are receiving any other investigational agents.
- Participants with known CNS lymphoma.
- Participants with known history of Human Immunodeficiency Virus (HIV), chronic
hepatitis B virus (HBV) or hepatitis C (HCV) requiring active treatment. Note:
Participants with serologic evidence of prior vaccination to HBV (i.e., HBs Ag-, and
anti-HBs+ and anti-HBC-) and positive anti-HBc from IVIG may participate.
- Concurrent administration of medications or foods that are moderate or strong
inhibitors or inducers of CYP3A within 7 days prior to first dose of study drug.
- Participants with chronic liver disease and hepatic impairment meeting Child-Pugh
class C (Appendix B).
- Concurrent administration of warfarin.
- Concurrent systemic immunosuppressant therapy within 21 days of the first dose of
study drug.
- Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug.
- Recent infection requiring systemic treatment that was completed ≤ 14 days before the
first dose of the study drug.
- Known bleeding disorders (e.g., congenital von Willebrand's disease or hemophilia)
- History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
- Major surgery within 4 weeks of first dose of study drug.
- Malabsorption syndrome or other condition that precludes enteral route of
administration.
- Female participants who are pregnant, breastfeeding, or planning to become pregnant
while enrolled in this study or within 90 days of last dose of study drug.
- Male participants who plan to father a child while enrolled in this study or within 90
days after the last dose of study drug
- Participants with known history of alcohol or drug abuse.
- Participants with inability to swallow pills.
- On any active therapy for other malignancies with the exception of topical therapies
for basal cell or squamous cell cancers of the skin.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.
- Participants with a history of non-compliance to medical regimens.
- Participants who are unwilling or unable to comply with the protocol.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Jorge J Castillo, MD, (617) 632-4218, [email protected]rd.edu
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT04273139
Organization ID
19-651
Responsible Party
Principal Investigator
Study Sponsor
Dana-Farber Cancer Institute
Collaborators
AbbVie
Study Sponsor
Jorge J Castillo, MD, Principal Investigator, Dana-Farber Cancer Institute
Verification Date
December 2020