Ibrutinib for Patients With Follicular Lymphoma Without Complete Response to Initial Chemoimmunotherapy

NCT02966730 | Terminated Early Phase 1 FDA Drug

• 1 other identifier: 16-396
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 9

Brief Summary

The purpose of this study is to find out how successful ibrutinib is at putting follicular lymphoma into full remission. In this study, remission will be determined by achieving a normal PET scan after treatment. A PET scan is an imaging test that looks for active lymphoma. People who don't have a complete remission on PET after their first treatment are at high risk for having their lymphoma return. This study will investigate if ibrutinib will help participants achieve a complete remission without giving additional chemotherapy. The study will also investigate any possible side effects of the study drug ibrutinib.

Conditions

Follicular Lymphoma; Follicular Lymphoma, Grade 1; Follicular Lymphoma, Grade 2; Follicular Lymphoma Grade IIIa

Keywords

follicular lymphoma; Ibrutinib; FLIPP; 16-396

Outcome Measures

Primary Outcomes (1)

• Rate of conversion from FDG-PET positive to negative

  The primary objective is to determine the rate of conversion from FDG-PET positive to negative at 12 months from the start of ibrutinib in patients receiving at least 6 months of Ibrutinib consolidation therapy for follicular lymphoma achieving at least a PR but remaining FDG-PET positive after first line chemoimmunotherapy.

  12 months

Study Arms (1)

Follicular Lymphoma

EXPERIMENTAL

Participants will be receive Ibrutinib as an oral capsule preparation once daily for a period of 2 years. The dose will be 560mg daily. Toxicities will be recorded and graded. Response to treatment will be determined by FDG-PET imaging every 6 months, or as clinically indicated, in conjunction with clinical assessment by a physician, including physical examination, every 4 weeks from day 1 (baseline) for the first 3 months and then every 3 months until the end of treatment at 2 years.

Drug: Ibrutinib

Interventions

Ibrutinib DRUG

Ibrutinib will be administered orally, on a once daily continuous dosing schedule and in an outpatient setting. Treatment will continue for 2 years and there will be no planned treatment breaks. The dose of Ibrutinib will be initiated at 560mg per day, which will remain constant throughout the study period, unless otherwise specified.

Follicular Lymphoma

Eligibility Criteria

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

You may qualify if:

• Follicular lymphoma with histology documented by the participating institution (grades 1, 2 or 3a).
• °For subjects with presumptive evidence of transformation based on clinical assessment of factors such as, but not limited to, increasing lactate dehydrogenase (LDH), rapidly worsening disease, or frequent B-symptoms, a pre-treatment biopsy is required to rule out large cell transformation
• Completion of a full course of first line immunochemotherapy including rituximab OR completion of 4 cycles of first line immunochemotherapy including rituximab if intolerant (e.g. which include, but are not limited to, R-CHOP, R-CVP, Bendamustine-R).
• Patients must have achieved PR to primary treatment and not be refractory to prior treatment.
• Residual FDG-PET activity defined as Deauville 4 or 5 on a PET-CT within 3 and 8 weeks post the last dose of front line therapy.
• Treatment must begin within 90 days of the last dose of immunochemotherapy.
• Men and women ≥ 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
• ≥ 1 measurable disease site on computed tomography (CT) scan or positron emission tomography (PET) (1.5 cm in longest dimension). (In select cases, for example extremity lesions, an MRI may be substituted.)
• Life expectancy of \> 3 months, in the opinion of the investigator.
• Female subjects who are of non-reproductive potential (i.e. post-menopausal by history - no menses for ≥ 2 years; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy). Female subjects of childbearing potential must have a negative serum pregnancy test upon study entry.
• Male and female subjects who agree to use highly effective methods of birth control (e.g., implants, injectables, combined oral contraceptives, some intrauterine devices \[IUDs\], sexual abstinence, or sterilized partner) and a barrier method (e.g. condoms, vaginal ring, sponge, etc) during the period of therapy and for 30 days (females) and 90 days (males) after the last dose of study drug.

You may not qualify if:

• Medically apparent central nervous system lymphoma or leptomeningeal disease.
• History of any other active malignancies.
• History of any prior cancer curatively treated within the last two years except:
• Any non-melanoma skin cancer
• Any cancer excised, not treated with chemotherapy and with less than a 30% chance of recurrence within the next 2 years from registration
• History of any organ transplantation.
• History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
• More than one prior line of any systemic chemoimmunotherapy for follicular lymphoma.
• Chemotherapy ≤ 21 days prior to first administration of study treatment and/or monoclonal antibody ≥ 3 weeks prior to first administration of study treatment.
• Prior exposure to radio- or toxin-immunoconjugates.
• Concurrent use of warfarin or other vitamin K antagonists.
• Concurrent use of a strong cytochrome P450 (CYP)3A4/5 inhibitor.
• Concurrent systemic immunosuppressant therapy (e.g., cyclosporine A, tacrolimus, etc., or chronic administration of \> 20 mg/day of prednisone) within 28 days of the first dose of study drug.
• Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug.
• Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree atrioventricular (AV) block type II, 3rd degree block, or corrected QT interval (QTc) \>/= 470 msec.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Fox Chase Cancer Center: collaborator
• Pharmacyclics LLC.: collaborator

Study Sites (9)

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Cancer Center @ Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan - Kettering Cancer Center

New York, New York, 10021, United States

Location

Memorial Sloan Kettering at Mercy Medical Center

Rockville Centre, New York, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Lymphoma, Follicular

Interventions

ibrutinib

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Ariela Noy, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 14, 2016
• First Posted: November 17, 2016
• Study Start: November 1, 2016
• Primary Completion: June 20, 2019
• Study Completion: June 20, 2019
• Last Updated: May 13, 2025

Record last verified: 2019-06

Locations

US (9)