Ibrutinib in Treating Patients With Relapsed or Refractory Follicular Lymphoma

Recurrent Grade 1 Follicular Lymphoma Clinical Trial

Official title:

Phase 2 Trial of Single-Agent Ibrutinib (PCI-32765) in Relapsed or Refractory Follicular Lymphoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02989532
• Other study ID #: NCI-2013-00887
• Secondary ID: NCI-2013-00887MC
• Status: Active, not recruiting
• Phase: Phase 2
• First received: December 8, 2016
• Last updated: December 8, 2016
• Start date: April 2013

Study information

• Verified date: December 2016
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This phase II trial studies how well ibrutinib works in treating patients with follicular lymphoma that has come back after a period of improvement or does not respond to treatment. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Description:

PRIMARY OBJECTIVES:

I. Evaluate the overall response rate of ibrutinib in patients with relapsed or refractory follicular lymphoma.

SECONDARY OBJECTIVES:

I. Assess the safety and tolerability of ibrutinib in patients with follicular lymphoma.

II. Evaluate overall survival, time to response, duration of response, progression-free survival, time to treatment failure, and time to subsequent treatment.

TERTIARY OBJECTIVES:

I. Describe the relationship between interim positron emission tomography (PET)/computed tomography (CT) scan results, CT response, and response duration.

II. Biomarker studies including exploring associations between ibrutinib response and somatic mutations identified in follicular lymphoma, whole transcriptome shotgun sequencing (ribonucleic acid-sequencing [RNA-seq]), exploration of inhibition of Bruton's tyrosine kinase (BTK) and other kinases, expression of cytokines, chemokines, and other proteins with an aim to develop predictors of response and resistance.

III. Assess changes in various cancer-derived molecules in the blood over the course of treatment with ibrutinib.

IV. As part of ongoing research for Phase II Consortium (P2C) studies, we are banking paraffin-embedded tissue blocks/slides and blood products for future studies.

OUTLINE:

Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with progressive disease at the end of course 2 may continue on therapy until the end of course 5 at the discretion of the treating physician.

After completion of study treatment, patients are followed up every 3 months until progressive disease, and then every 6 months for 5 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 41
• Est. primary completion date: October 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed diagnosis of follicular lymphoma, grade 1, 2, or 3a; NOTE:

fresh (frozen) tumor biopsy must be available or attempted; a frozen tumor biopsy equivalent to a minimum of four at least 16 gauge needle cores is an important component of this study; patients without adequate frozen material should have a biopsy performed to obtain material; if biopsy is performed and does not yield adequate material, the patient is still eligible for the study; if a biopsy cannot be done safely, the patient may still be eligible for the study if permission is granted in writing (email) by the study chair (Dr. Nancy Bartlett) or her designees; Dr. Bartlett may be consulted to discuss situations involving invasive biopsy procedures that may pose an increased risk to the patient

• Measureable disease as defined by a lymph node or tumor mass that is >= 1.5 cm in at least one dimension by CT or the CT portion of the PET/CT

• Relapsed or refractory follicular lymphoma which has progressed during or following 1 or more prior chemotherapy regimens for lymphoma

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2

• Absolute neutrophil count >= 750/mm^3 (0.75 x 10^9/L)

• Hemoglobin >= 8.0 g/dL

• Platelets >= 30,000/mm^3 (30 x 10^9/L)

• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) unless Gilbert's syndrome or disease infiltration of the liver is present

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.0 x institutional ULN

• Creatinine =< 2.0 x institutional ULN

• Creatinine clearance (estimated [est.] glomerular filtration rate [GFR] Cockcroft-Gault) >= 30 mL/min

• Negative serum pregnancy test done =< 7 days prior to registration for women of childbearing potential only

• Ability to understand and the willingness to sign a written informed consent document

• Willingness to provide biologic samples for correlative research purposes

Exclusion Criteria:

• Any of the following:

• Chemotherapy/systemic therapy =< 4 weeks prior to registration

• Radiotherapy =< 4 weeks prior to registration

• Nitrosoureas or mitomycin C =< 6 weeks prior to registration

• Those who have not recovered from adverse events due to agents administered more than 4 weeks earlier

• Major surgery =< 10 days prior to registration or minor surgery =< 7 days prior to registration

• Prior therapy with ibrutinib or another Bruton's tyrosine kinase inhibitor

• Receiving any other investigational agents

• Active central nervous system (CNS) involvement

• Receiving any medications or substances that are strong inhibitors or inducers of cytochrome P450 family 3 subfamily A member 4/5 (CYP3A4/5)

• Any of the following:

• Pregnant women

• Nursing women

• Men or women of childbearing potential who are unwilling to employ adequate contraception

• NOTE: women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of ibrutinib administration

• NOTE: breastfeeding should be discontinued if the mother is treated with ibrutinib

• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy; NOTE: HIV-positive patients who are not on anti-viral medications that are strong CYP3A4/5 inhibitors and who do not have cluster of differentiation (CD)4 counts less than the lower limit of normal by institutional criteria are eligible; no patients with CD4 counts below institutional normals are eligible

• Known active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV)

• Known histological transformation from follicular lymphoma to diffuse large B-cell lymphoma; NOTE: a prior history of adequately treated transformed lymphoma does not exclude a patient if the current active disease is biopsy-proven follicular lymphoma

• History of stroke or intracranial hemorrhage =< 6 months prior to the first dose of study drug

• Requires anticoagulation with warfarin or similar vitamin K antagonist; NOTE:

warfarin or similar vitamin K antagonist must have been discontinued at least 28 days prior to study entry

• Patient has the inability to swallow tablets

• Uncontrolled intercurrent illness including, but not limited to:

• Ongoing or active infection,

• Uncontrolled diabetes mellitus

• Cardiac disease

• Psychiatric illness/social situations that would limit compliance with study requirements

• "Currently active" second malignancy, other than non-melanoma skin cancers; NOTE:

patients are not considered to have a "currently active" malignancy if they have completed anti-cancer therapy, and are considered by their physician to be at less than 30% risk of relapse

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ibrutinib

• Concurrent treatment with therapeutic doses (> 20 mg prednisone or equivalent) of systemic steroids within 14 days of start of protocol therapy

• Prior history of allogeneic stem cell transplant

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Follicular
• Recurrent Grade 1 Follicular Lymphoma
• Recurrent Grade 2 Follicular Lymphoma
• Recurrent Grade 3 Follicular Lymphoma
• Refractory Follicular Lymphoma

Intervention

Drug:
• Ibrutinib
Given PO

Other:
• Laboratory Biomarker Analysis
Correlative studies

Locations

Country	Name	City	State
Canada	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario
Canada	Cancer Centre of Southeastern Ontario at Kingston General Hospital	Kingston	Ontario
Canada	University Health Network-Princess Margaret Hospital	Toronto	Ontario
Singapore	National Cancer Centre	Singapore
Singapore	National University Hospital Singapore	Singapore
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Metro Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Mayo Clinic in Arizona	Scottsdale	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada,  Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rate defined as a partial response (PR) or complete response (CR) as the objective status at any time during treatment, evaluated using the Cheson et al. Revised Response Criteria for Malignant Lymphoma	Ninety-five percent binomial confidence intervals for the true success proportion will be calculated.	Up to 5 years	No
Secondary	Duration of response	Estimated using the method of Kaplan-Meier.	Time from the date at which the patient's objective status is first noted to be a CR or PR to the earliest date progression is documented, assessed up to 5 years	No
Secondary	Overall survival	Estimated using the method of Kaplan-Meier.	Time from registration to death due to any cause, assessed up to 5 years	No
Secondary	Progression-free survival	Estimated using the method of Kaplan-Meier.	Time from registration to progression or death due to any cause, assessed up to 5 years	No
Secondary	Time to response	The median and range will be reported.	Time from the date of registration to the date at which the patient's objective status is first noted to be a CR or PR, assessed up to 5 years	No
Secondary	Time to subsequent treatment	Estimated using the method of Kaplan-Meier.	Time from registration to the date of initiation of subsequent treatment for lymphoma, assessed up to 5 years	No
Secondary	Time to treatment failure	Estimated using the method of Kaplan-Meier.	Time from registration to the date of treatment discontinuation due to any reason, assessed up to 5 years	No