Ibrutinib and Venetoclax in Relapsed and Refractory Follicular Lymphoma

NCT02956382 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 2016-0014
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 3

Brief Summary

This is a phase I/II study in which patients will be enrolled in a standard 3+3 design. Once the maximum tolerated dose (MTD) is determined amongst patients with relapsed or refractory grade 1-3a follicular lymphoma, there will be a 17-patient phase II study.

Conditions

Refractory Follicular Lymphoma; Relapsed Follicular Lymphoma

Keywords

Ibrutinib; Venetoclax; Follicular; Refractory; Relapsed; Lymphoma

Outcome Measures

Primary Outcomes (2)

• Recommended Phase 2 Dose (RP2D)

  The maximum tolerated dose of Ibrutinib and Venetoclax as determined by number of DLTs observed. • If 0/3 DLT is observed, dose escalation will continue to the next upper dose level. • If ≥ 2/3 DLTs are observed, then the dose finding procedure will be terminated. • If 1/3 DLT is observed, then 3 additional patients will be enrolled in the same dose level. If no DLT is observed from the additional 3 patients, then dose escalation will continue to the next upper dose level. If any DLT is observed from the 3 additional patients, then the previously lower dose will be chosen as the MTD and the dose finding procedure will be terminated.

  Cycle 1 (28 days)

• Dose Level 2 Overall Response Rate

  Number of participants on the recommended phase II dose level 2, with a partial or complete response, as determined by the revised Lugano Response Criteria for Non-Hodgkin Lymphoma,

  36 months

Secondary Outcomes (4)

• Pharmacokinetics of Ibrutinib (Cmax) Phase 1

  Cycle 1 (28 days)

• Pharmacokinetics of Ibrutinib (Tmax) Phase 1

  Cycle 1 (28 days)

• Pharmacokinetics of Ibrutinib (AUC) Phase 1

  Cycle 1 (28 days)

• Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.03

  36 months

Study Arms (5)

Phase I - Dose Level 0

EXPERIMENTAL

Ibrutinib (capsule) - 420mg Venetoclax (tablet) - 400mg Each medication is taken daily. Treatment cycles are 28 days long.

Drug: Ibrutinib; Drug: Venetoclax

Phase I - Dose Level 1

EXPERIMENTAL

Ibrutinib (capsule) - 560mg Venetoclax (tablet) - 400mg Each medication is taken daily. Treatment cycles are 28 days long.

Drug: Ibrutinib; Drug: Venetoclax

Phase I - Dose Level 2

EXPERIMENTAL

Ibrutinib (capsule) - 560mg Venetoclax (tablet) - 600mg Each medication is taken daily. Treatment cycles are 28 days long.

Drug: Ibrutinib; Drug: Venetoclax

Phase I - Dose Level 3

EXPERIMENTAL

Ibrutinib (capsule) - 560mg Venetoclax (tablet) - 800mg Each medication is taken daily. Treatment cycles are 28 days long.

Drug: Ibrutinib; Drug: Venetoclax

Phase II Dose

EXPERIMENTAL

The Phase II dose will be the maximum tolerated dose as determined in the Phase I portion.

Drug: Ibrutinib; Drug: Venetoclax

Interventions

Ibrutinib DRUG

Ibrutinib is dispensed as a capsule.

Also known as: PCI-32765

Phase I - Dose Level 0; Phase I - Dose Level 1; Phase I - Dose Level 2; Phase I - Dose Level 3; Phase II Dose

Venetoclax DRUG

Venetoclax is dispensed as a tablet.

Also known as: ABT-199

Phase I - Dose Level 0; Phase I - Dose Level 1; Phase I - Dose Level 2; Phase I - Dose Level 3; Phase II Dose

Eligibility Criteria

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

You may qualify if:

• Relapsed or refractory, histologically confirmed follicular lymphoma, grade I, II, or IIIa which requires therapy defined by at least one of the following:
• Constitutional symptoms
• Cytopenias
• High tumor burden (single mass \> 7 cm, three masses \> 3 cm, symptomatic splenomegaly, organ compression or compromise, ascites, pleural effusion)Must have received at least two prior systemic therapies
• All risk by FLIPI 0-5 factors (Appendix I)
• Measurable disease Measurable disease must be present either on physical examination or imaging studies; non-measurable disease alone is not acceptable. Any tumor mass \> 1.5 cm is acceptable.
• Lesions that are considered non-measurable include the following:
• Bone lesions (lesions if present should be noted)
• Ascites
• Pleural/pericardial effusion
• Lymphangitis cutis/pulmonis
• Bone marrow (involvement by lymphoma should be noted)
• Adequate hematologic function independent of transfusion and growth factor support for at least 3 weeks prior to screening unless attributable to disease. Defined as:
• Absolute neutrophil count (ANC) \>1000 cells/mm3 (1.0 x 109/L). ANC \> 500 cells/mm3 is permissible if due to disease.
• Platelet count \>50,000 cells/mm3 (50 x 109/L) unless attributable to disease. Platelet count \> 20,000 cells/mm3 is permissible if due to disease.

You may not qualify if:

• Chemotherapy, monoclonal antibody, or small molecule kinase inhibitor less than or equal 21 days prior to first administration of study treatment
• Prior exposure to a Bruton's tyrosine kinase (BTK) or B-cell lymphoma 2 (BCL-2) inhibitor.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ibrutinib or venetoclax.
• Known allergy to xanthine oxidase inhibitors and/or rasburicase for subjects at risk for tumor lysis syndrome.
• History of other malignancies, except:
• Malignancy treated with curative intent and with no known active disease present for ≥ 3 years before the first dose of study drug and felt to be at low risk for recurrence by treating physician.
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
• Adequately treated carcinoma in situ without evidence of disease.
• Concurrent systemic immunosuppressant therapy (e.g., cyclosporine A, tacrolimus, etc., or chronic administration \[\>14 days\] of \> 20 mg/day of prednisone) within 28 days of the first dose of study drug.
• Undergone an allogeneic stem cell transplant within the past 1 year.
• Current or history of graft versus host disease
• 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 study drug.
• Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia.
• History of stroke or intracranial hemorrhage within 6 months prior to enrollment.

Sponsors & Collaborators

• Georgetown University: lead
• AbbVie: collaborator
• Pharmacyclics LLC.: collaborator
• Hackensack Meridian Health: collaborator

Study Sites (3)

Georgetown Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, 20007, United States

Location

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Lymphoma, Follicular; Recurrence; Lymphoma

Interventions

ibrutinib; venetoclax

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Chaitra Ujjani, MD
• Organization: Seattle Cancer Care Alliance

ujjani@uw.edu

(206) 606-1955

Study Officials

• Chaitra Ujjani, MD

  Seattle Cancer Care Alliance

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2016
• First Posted: November 7, 2016
• Study Start: March 1, 2017
• Primary Completion: May 23, 2023
• Study Completion: March 7, 2024
• Last Updated: July 18, 2025
• Results First Posted: May 21, 2024

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)