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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 : June 19, 2018
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:

Background:

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).

Objective:

To study the safety of ViPOR for people with B-cell lymphoma.

Eligibility:

People ages 18 and older with B-cell lymphoma whose cancer has returned or not improved after treatment

Design:

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

Expanded Access : National Cancer Institute (NCI) has indicated that access to an investigational treatment associated with this study is available outside the clinical trial.  

Detailed Description:

Background:

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.

Objectives:

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

Eligibility:

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

Design:

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

To explore all dose levels, including further evaluation in a dose expansion of up to 10 additional patients at the MTD, the accrual ceiling will be set at 45 patients.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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


Arm Intervention/treatment
Experimental: Arm 1 Dose Escalation
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
Drug: Venetoclax
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 toxicity

Drug: Ibrutinib
Administered orally, days 1-14, at a dose of 560mg; every 21 days for up to 6 cycles, or unacceptable toxicity

Drug: 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 toxicity

Drug: Obinutuzumab
Administered intraveneously, days 1 and 2, at a dose of 1000 mg; every 21 days for up to 6 cycles, or until unacceptable toxicity

Drug: 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

Experimental: Arm 2 Dose Escalation/ Expansion
ViPOR (venetoclax, ibrutinib, prednisone, obinutuzumab, lenalidomide) for cycles 1-6
Drug: Venetoclax
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 toxicity

Drug: Ibrutinib
Administered orally, days 1-14, at a dose of 560mg; every 21 days for up to 6 cycles, or unacceptable toxicity

Drug: 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 toxicity

Drug: Obinutuzumab
Administered intraveneously, days 1 and 2, at a dose of 1000 mg; every 21 days for up to 6 cycles, or until unacceptable toxicity

Drug: 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




Primary Outcome Measures :
  1. Number and grade of adverse events [ Time Frame: 22 days ]
    Number and grade of adverse events


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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



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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • ELIGIBILITY CRITERIA:
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03223610


Contacts
Contact: Maureen E Edgerly, R.N. (240) 760-6013 edgerlym@pbmac.nci.nih.gov

Locations
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      
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Christopher J Melani, M.D. National Cancer Institute (NCI)

Additional Information:
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT03223610     History of Changes
Other Study ID Numbers: 170127
17-C-0127
First Posted: July 21, 2017    Key Record Dates
Last Update Posted: June 19, 2018
Last Verified: June 15, 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Monoclonal Antibody
Dose-Finding

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Burkitt Lymphoma
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Prednisone
Lenalidomide
Obinutuzumab
Venetoclax
Thalidomide
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Immunologic Factors
Angiogenesis Inhibitors