Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Revlimid (ViPOR) in Relapsed/Refractory B-cell Lymphoma

NCT03223610 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 17012717-C-0127
• Study Type: interventional
• Target: 155
• Locations: 1 country
• Sites: 1

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.

Conditions

Lymphoma; Non-Hodgkin Lymphoma; Diffuse Large B-Cell Lymphoma; Burkitt Lymphoma

Keywords

Monoclonal Antibody; Dose-Finding

Outcome Measures

Primary Outcomes (1)

• Number and grade of adverse events

  Number and grade of adverse events

  22 days

Secondary Outcomes (3)

• Progression-free survival (PFS)

  Time from the date of study enrollment until time of disease relapse, disease progression, or death, whichever occurs first, assessed every 3-6 months

• Overall survival (OS)

  Time from the date of from initial diagnosis until death from any cause; assessed every 3-6 months

• Overall response rate (ORR)

  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

Study Arms (4)

Arm 1: Dose Escalation

EXPERIMENTAL

iPOR (ibrutinib, prednisone, obinutuzumab, lenalidomide) for cycle 1; followed by ViPOR (venetoclax, ibrutinib, prednisone, obinutuzumab, lenalidomide) for cycles 2-6

Drug: Venetoclax; Drug: Ibrutinib; Drug: Prednisone; Biological: Obinutuzumab; Drug: Revlimid (lenalidomide)

Arm 2: Dose Escalation

EXPERIMENTAL

ViPOR (venetoclax, ibrutinib, prednisone, obinutuzumab, lenalidomide) for cycles 1-6

Drug: Venetoclax; Drug: Ibrutinib; Drug: Prednisone; Biological: Obinutuzumab; Drug: Revlimid (lenalidomide)

Arm 3: Dose Expansion

EXPERIMENTAL

ViPOR (venetoclax, ibrutinib, prednisone, obinutuzumab, lenalidomide) for cycles 1-6

Drug: Venetoclax; Drug: Ibrutinib; Drug: Prednisone; Biological: Obinutuzumab; Drug: Revlimid (lenalidomide)

Arm 4: Dose Expansion

EXPERIMENTAL

iPOR (ibrutinib, prednisone, obinutuzumab, lenalidomide) for cycle 1; followed by ViPOR (venetoclax, ibrutinib, prednisone, obinutuzumab, lenalidomide) for cycles 2-6

Drug: Venetoclax; Drug: Ibrutinib; Drug: Prednisone; Biological: Obinutuzumab; Drug: Revlimid (lenalidomide)

Interventions

Venetoclax DRUG

Administered orally, days 2-14, at varying doses of 200-800 mg (based upon assigned dose level); every 21 days for up to 6 cycles, or until disease progression or unacceptable toxicity

Arm 1: Dose Escalation; Arm 2: Dose Escalation; Arm 3: Dose Expansion; Arm 4: Dose Expansion

Ibrutinib DRUG

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

Arm 1: Dose Escalation; Arm 2: Dose Escalation; Arm 3: Dose Expansion; Arm 4: Dose Expansion

Obinutuzumab BIOLOGICAL

Administered intravenously, days 1 and 2, at a dose of 1000 mg; every 21 days for up to 6 cycles, or until disease progression or unacceptable toxicity

Arm 1: Dose Escalation; Arm 2: Dose Escalation; Arm 3: Dose Expansion; Arm 4: Dose Expansion

Revlimid (lenalidomide) DRUG

Administered orally, days 1-15, at a dose of 15 mg; every 21 days for up to 6 cycles, or until disease progression or unacceptable toxicity

Arm 1: Dose Escalation; Arm 2: Dose Escalation; Arm 3: Dose Expansion; Arm 4: Dose Expansion

Prednisone DRUG

Administered orally, days 1-7, at a dose of 100 mg; every 21 days for up to 6 cycles, or until disease progression or unacceptable toxicity

Arm 1: Dose Escalation; Arm 2: Dose Escalation; Arm 3: Dose Expansion; Arm 4: Dose Expansion

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed B-cell lymphoma confirmed by the Laboratory of Pathology, NCI, as follows:
• Phase1b
• Aggressive B-cell lymphoma: includes DLBCL and subtypes, transformed lymphoma, Burkitt lymphoma, as well as High-grade B-cell lymphoma with MYC and/or BCL2 and/or BCL6 rearrangement(s).
• Indolent B-cell lymphoma:
• CLL/SLL is excluded given alternative dosing of FDA-approved venetoclax for relapsed 17p CLL and increased risk of TLS with CLL/SLL compared to other non-Hodgkin lymphomas.
• NOTE: Patients with known active CNS lymphoma are not eligible.
• Phase 2
• Relapsed and/or refractory DLBCL and subtypes, including transformed lymphoma as well as High grade B-cell lymphoma with MYC and/or BCL2 and/or BCL6 rearrangement(s).
• Relapsed and/or refractory Follicular lymphoma (FL)
• Relapsed and/or refractory and untreated Mantle cell lymphoma (MCL)
• Relapsed and/or refractory disease on at least 1 prior treatment regimen, as follows:
• Aggressive B-cell lymphoma:relapsed after and/or refractory to at least 1 prior anthracycline-containing regimen
• Indolent B-cell lymphoma: relapsed after and/or refractory to at least 1 prior anti-CD20 antibody-containing regimen.
• NOTE: Patients with untreated and relapsed and/or refractory MCL will be included in the phase 2 MCL expansion.
• Patients must have evaluable disease by clinical exam (i.e. palpable lymphadenopathy, measurable skin lesions, etc.), laboratory assessment (i.e. lymphoma involvement of bone marrow or peripheral blood by morphology, cytology or flow cytometry), and/or imaging (measurable lymph nodes or masses on CT or MRI and/or evaluable FDG-avid lesions on PET).

You may not qualify if:

• The following restrictions apply to current or prior anti-cancer treatment, prior to the first dose of study drug:
• Patients who are actively receiving any other investigational agents.
• Any chemotherapy, external beam radiation therapy, or anti-cancer antibodies within 2 weeks prior to the first dose of study drug
• Radio- or toxin-immunoconjugates within 10 weeks prior to the first dose of study drug
• Previous treatment with greater than one of the study agents (i.e., venetoclax, ibrutinib or Revlimid(R)), excluding prior prednisone or anti-CD20 antibody treatment
• Prior allogeneic stem cell (or other organ) transplant within 6 months or any evidence of active graft-versus-host disease or requirement for immunosuppressants within 28 days prior to first dose of study drug
• Not recovered (i.e., less than or equal to Grade 1 or baseline) from adverse events due to previously administered anti-cancer treatment, surgery, or procedure. NOTE: Exceptions to this include events not considered to place the subject at unacceptable risk of participation in the opinion of the PI (e.g., alopecia).
• Patients requiring the use of warfarin are excluded because of potential drug-drug interactions that may potentially increase the exposure of warfarin.
• Patients requiring the following agents within 7 days prior to the first dose of venetoclax are excluded:
• Strong CYP3A inhibitors
• Strong CYP3A inducers
• NOTE: Moderate CYP3A inhibitors and inducers should be used with caution and an alternative medication used, whenever possible.
• Uncontrolled intercurrent illness including, but not limited to the following that may limit interpretation of results or that could increase risk to the patient at the discretion of the investigator:
• Symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia
• Uncontrolled and/or symptomatic thyroid disease

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (1)

• Melani C, Lakhotia R, Pittaluga S, Phelan JD, Huang DW, Wright G, Simard J, Muppidi J, Thomas CJ, Ceribelli M, Tosto FA, Yang Y, Xu W, Davies-Hill T, Pack SD, Peer CJ, Arisa O, Mena E, Lindenberg L, Bergvall E, Portell CA, Farah RJ, Lee ST, Pradhan A, Morrison C, Tadese A, Juanitez AM, Lu C, Jacob A, Simmons H, Figg WD, Steinberg SM, Jaffe ES, Roschewski M, Staudt LM, Wilson WH. Combination Targeted Therapy in Relapsed Diffuse Large B-Cell Lymphoma. N Engl J Med. 2024 Jun 20;390(23):2143-2155. doi: 10.1056/NEJMoa2401532.

  PMID: 38899693 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, Large B-Cell, Diffuse; Burkitt Lymphoma

Interventions

venetoclax; ibrutinib; Prednisone; obinutuzumab; Lenalidomide

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Christopher J Melani, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

NCIMO Referral Office

CONTACT

(888) 624-1937; ncimo_referrals@mail.nih.gov

Christopher J Melani, M.D.

CONTACT

(240) 760-6057; christopher.melani@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2017
• First Posted: July 21, 2017
• Study Start: February 9, 2018
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: June 5, 2026

Record last verified: 2026-03-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data will be available during the study and indefinitely. @@@@@@@@@@@@Genomic data will be available once genomic data are uploaded per protocol GDS plan for as long as database is active.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI. @@@@@@@@@@@@Genomic data will be made available via dbGaP through requests to the data custodians.

Locations

US (1)