Grade 3a Follicular LymphomaPhase 2NCT01849263
Ibrutinib in Treating Patients With Relapsed or Refractory Follicular Lymphoma
A Phase 2 study testing Ibrutinib and Laboratory Biomarker Analysis in people with Grade 3a Follicular Lymphoma and Recurrent Grade 1 Follicular Lymphoma, run by National Cancer Institute (NCI) at 13 sites in 3 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Grade 3a Follicular Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma
- What is being tested?
- Ibrutinib and Laboratory Biomarker Analysis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 13 sitesin 3 countries
- Study dates
- 2 Apr 2013to 19 Mar 2027
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- Measurable 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)
Show all 15Show fewer
- 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
Who cannot join
- 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
Show all 35Show fewer
- 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 antiretroviral therapy are ineligible; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
- 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
Trial locations and contacts
13 sites in 3 countries.
13 sites in 3 countries
United States8 sites
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
Metro Minnesota Community Oncology Research Consortium
Saint Louis Park, Minnesota, 55416
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park, Minnesota, 55416
Mayo Clinic in Arizona
Scottsdale, Arizona, 85259
Washington University School of Medicine
St Louis, Missouri, 63110
Canada3 sites
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, L8V 5C2
Kingston Health Sciences Centre
Kingston, Ontario, K7L 2V7
University Health Network-Princess Margaret Hospital
Toronto, Ontario, M5G 2M9
Singapore2 sites
National University Hospital Singapore
Singapore, 119074
National Cancer Centre Singapore
Singapore, 168583
About this study
Official title: Phase 2 Trial of Single-Agent Ibrutinib (PCI-32765) in Relapsed or Refractory Follicular Lymphoma
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.
Read the detailed description
PRIMARY OBJECTIVES:
- Evaluate the overall response rate of ibrutinib in patients with relapsed or refractory follicular lymphoma.
SECONDARY OBJECTIVES:
- 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:
- 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.
- Conditions
- Grade 3a Follicular Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Refractory Follicular Lymphoma
- Being tested
- Ibrutinib, Laboratory Biomarker Analysis
- Medical subject headings
- Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IbrutinibDrug
Also called BTK Inhibitor PCI-32765, CRA 032765, CRA-032765, CRA032765
Given PO
Laboratory Biomarker AnalysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (ibrutinib) | Experimental | Patients receive ibrutinib PO 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. Receives: Drug: Ibrutinib; Other: Laboratory Biomarker Analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate
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.
A CR is defined as the disappearance of all evidence of disease. A PR is defined as ≥ 50% decrease in the sum of the products of dimensions (SPD) of up to 6 largest dominant masses; no increase in size of other nodes and regression on CT, and no increase in size of liver/spleen.
Measured: Up to 5 years
Secondary outcomes (6)
Duration of Response
Duration of response is defined as the time from first evidence of a response to the first documented time of progressive disease (PD). Response and Progression were assessed using the Cheson et al. Revised Response Criteria for Malignant Lymphoma. > > A CR is defined as the disappearance of all evidence of disease. A PR is defined as ≥ 50% decrease in the sum of the products of dimensions (SPD) of up to 6 largest dominant masses; no increase in size of other nodes and regression on CT, and no increase in size of liver/spleen.Estimated using the method of Kaplan-Meier.>
> Progressive Disease (PD) is defined as any new lesion or increase by ≥ 50% of previously involved sites from nadir.
Measured: 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
Overall Survival
Overall Survival is defined as the time from registration to death due to any cause. Estimated using the method of Kaplan-Meier.
Measured: Assessed up to 5 years
Progression-free Survival
Progression-Free Survival is defined as the time from registration to documented progression or death due to any cause, whichever occurs first. Estimated using the method of Kaplan-Meier.
Measured: Time from registration to progression or death due to any cause, assessed up to 5 years
Time to Response
Time to response is defined for all evaluable patients who have achieved a confirmed response as the 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.The median and 95% confidence interval will be calculated using the methods of Kaplan-Meier.
Measured: 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
Time to Subsequent Treatment
Time to subsequent treatment is defined as the time from registration to the date of initiation of subsequent treatment for lymphoma. The distribution of time to subsequent treatment will be estimated using the method of Kaplan-Meier.
Measured: Time from registration to the date of initiation of subsequent treatment for lymphoma, assessed up to 5 years
Time to Treatment Failure
Time to treatment failure is defined as the time from registration to the date of treatment discontinuation due to any reason. The distribution of time to treatment failure will be estimated using the method of Kaplan-Meier.
Measured: Time from registration to the date of treatment discontinuation due to any reason, assessed up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2013 (estimated)
- Study start2 Apr 2013
- Primary completion3 Jun 2016
- Study completion19 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Grade 3a Follicular LymphomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Nancy L Bartlett, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01849263
- Sponsor's protocol ID
- NCI-2013-00887
- Other IDs
- NCI-2013-00887, MC1282, 9271, 9271, N01CM00032, N01CM00099, P30CA015083, U10CA180821
- Status last verified
- Sep 2026
- First submitted
- 6 May 2013
- Last updated
- 11 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Bartlett NL, Costello BA, LaPlant BR, Ansell SM, Kuruvilla JG, Reeder CB, Thye LS, Anderson DM, Krysiak K, Ramirez C, Qi J, Siegel BA, Griffith M, Griffith OL, Gomez F, Fehniger TA. Single-agent ibrutinib in relapsed or refractory follicular lymphoma: a phase 2 consortium trial. Blood. 2018 Jan 11;131(2):182-190. doi: 10.1182/blood-2017-09-804641. Epub 2017 Oct 26.
PubMed 29074501