Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Revlimid (ViPOR) in Relapsed/Refractory B-cell Lymphoma
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|ClinicalTrials.gov Identifier: NCT03223610|
Recruitment Status : Recruiting
First Posted : July 21, 2017
Last Update Posted : March 7, 2018
B-cell lymphoma is a cancer of white blood cells found in the lymph nodes. It affects the system that fights infections and disease. Researchers want to learn how certain drugs work together to treat B-cell lymphomas. The drugs are venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide (ViPOR).
To study the safety of ViPOR for people with B-cell lymphoma.
People ages 18 and older with B-cell lymphoma whose cancer has returned or not improved after treatment
Participants will be screened with:
- Medical history
- Physical exam
- Blood, urine, and heart tests
- Tissue sample from previous procedure
- Imaging scans
- Registration for counseling on the risks of lenalidomide. They must get counseling at least every 28 days.
Participants will have a bone marrow aspiration before treatment.
Participants may have tumor samples taken.
Participants will get ViPOR in 21-day cycles. For up to 6 cycles:
- Participants will get one drug by IV on days 1 and 2.
- Participants will take the other four drugs by mouth on most days. After their first dose of venetoclax, they will stay in the clinic for at least 8 hours and return the next day for monitoring. They may be admitted for more drugs or monitoring.
Participants will keep a drug diary.
Participants will have a physical exam and blood and urine tests at least once per cycle. They will have scans 4 times over 6 cycles.
Participants will have a visit about 1 month after their last dose of study drug. They will then have visits every few months for 3 years, and once a year for years 4 and 5. Visits include a physical exam, blood tests, and scans.
|Condition or disease||Intervention/treatment||Phase|
|Lymphoma Non-Hodgkin Lymphoma Diffuse Large B-Cell Lymphoma Burkitt Lymphoma||Drug: Venetoclax Drug: Ibrutinib Drug: Prednisone Drug: Obinutuzumab Drug: Revlimid (lenalidomide)||Phase 1|
National Cancer Institute (NCI) has indicated that access to an investigational treatment associated with this study is available outside the clinical trial.
Combination chemotherapy with Rituximab has been the mainstay of treatment for CD20- positive B-cell lymphomas
Significant advances have been made in curing aggressive B-cell lymphomas with chemoimmunotherapy but indolent lymphomas and relapsed/refractory aggressive lymphomas remain mostly incurable with chemotherapy alone
Targeted therapies aimed at disrupting key survival pathways in lymphoid malignancies are emerging and showing significant activity in NHL in both the relapsed and first-line settings
Mechanistically-based combinations of targeted agents are likely to benefit patients who cannot tolerate or who relapse after or are refractory to standard chemoimmunotherapy
ViPOR targets major survival pathways in B-cell lymphomas including BCL-2 (apoptosis); BTK (B-cell receptor signaling and NFKB); Cereblon (NFKB) and CD20.
To determine the maximum tolerated dose (MTD) and the safety and toxicity profile of the combination of Venetoclax, Ibrutinib, Prednisone, Obinutuzumab and Revlimid in relapsed/refractory B-cell malignancies
Women and men greater than or equal to 18 years of age
ECOG performance status of less than or equal to 2
Histologically or cytologically confirmed relapsed and/or refractory B-cell lymphoma, excluding MCL and CLL/SLL
Adequate organ function unless dysfunction secondary to lymphoma effect
Open-label, single-center, non-randomized phase 1b study
Standard 3 x 3 design will be used to determine the MTD of dose-escalated venetoclax with fixed dose ibrutinib, prednisone, obinutuzumab and Revlimid with a small expansion cohort at the MTD.
Maximum 6 cycles of combination targeted therapy every 21 days
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||38 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase 1b Study of Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Revlimid (ViPOR) in Relapsed/Refractory B-cell Lymphoma|
|Actual Study Start Date :||February 9, 2018|
|Estimated Primary Completion Date :||March 1, 2019|
|Estimated Study Completion Date :||September 1, 2022|
Venetoclax (PO, days 2-14), Ibrutinib (PO, days 1-14),Prednisone (PO, days 1-7), Obinutuzumab (IV, days 1 and 2), and Revlimid (lenalidomide) (PO, days 1-15) given in combination every 21 days for up to 6 cycles, or until disease progression or unacceptable toxicity
Administered orally, days 2-14, at varying doses of 200-800mg (based upon assigned dose level); every 21 days for up to 6 cycles, or until disease progression or unacceptable toxicityDrug: Ibrutinib
Administered orally, days 1-14, at a dose of 560mg; every 21 days for up to 6 cycles, or unacceptable toxicityDrug: Prednisone
Administered orally, days 1-7, at a dose of 100mg; every 21 days for up to 6 cycles, or until disease progression or unacceptable toxicityDrug: Obinutuzumab
Administered intraveneously, days 1 and 2, at a dose of 1000 mg; every 21 days for up to 6 cycles, or until unacceptable toxicityDrug: Revlimid (lenalidomide)
Administered orally, days 1-15, at a dose of 15mg; every 21 days for up to 6 cycles, or until disease progression or unacceptable toxicity
- Number and grade of adverse events [ Time Frame: 22 days ]
- Overall response rate (ORR) [ Time Frame: assessed every 3-6 months ]Time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented or death, assessed every 3-6 months
- Progressive-free survival (PFS) [ Time Frame: assessed every 3-6 months ]Time from the date of study enrollment until the time of disease relapse, disease progression, or death, whichever occurs first, assessed every 3-6 months
- Overall survival (OS) [ Time Frame: assesed every 3-6 ]Time from the date of from initial diagnosis until death from any cause; assesed every 3-6
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03223610
|Contact: Maureen E Edgerly, R.N.||(240) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937|
|Principal Investigator:||Christopher J Melani, M.D.||National Cancer Institute (NCI)|