Trial Outcomes & Findings for Ibrutinib in Combination With Rituximab and Lenalidomide in Treating Patients With Previously Untreated, Stage II-IV Follicular Lymphoma or Marginal Zone Lymphoma (NCT NCT02532257)

Last Updated: 2024-09-24

Results Overview

Evaluate the efficacy of ibrutinib combined with rituximab and lenalidomide in patients with previously untreated FL and marginal zone lymphoma (determined by PFS at 2 years). Response will be assessed by the investigator based on the 2014 Cheson Lugano criteria. The 2-year PFS rate will be calculated and corresponding 95% confidence interval (CI) will be derived. Kaplan-Meier method will be used to estimate the PFS. Corresponding 95% CI will be summarized. Cox proportional hazards models will be used to assess the effects of patient prognostic factors on time-to-event endpoints.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

48 participants

Primary outcome timeframe

24 months

Results posted on

2024-09-24

Participant Flow

Participant milestones

Participant milestones
Measure	Arm 1 38 particpants previously untreated Follicular Lymphoma, 10 Marginal Zone Lymphoma
Overall Study STARTED	48
Overall Study Previously Untreated Follicular Lymphoma FL Grade 1-3a	38
Overall Study Marginal Zone	10
Overall Study COMPLETED	29
Overall Study NOT COMPLETED	19

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm 1 38 particpants previously untreated Follicular Lymphoma, 10 Marginal Zone Lymphoma
Overall Study Adverse Event	2
Overall Study Physician Decision	4
Overall Study Withdrawal by Subject	3
Overall Study Progressive Disease	10

Baseline Characteristics

Ibrutinib in Combination With Rituximab and Lenalidomide in Treating Patients With Previously Untreated, Stage II-IV Follicular Lymphoma or Marginal Zone Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm 1 n=48 Participants 38 participants previously untreated Follicular Lymphoma, 10 Marginal Zone Lymphoma
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	33 Participants n=5 Participants
Age, Categorical >=65 years	15 Participants n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants
Sex: Female, Male Male	32 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	43 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	38 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants
Region of Enrollment United States	48 participants n=5 Participants

PRIMARY outcome

Timeframe: 24 months

Population: 38 participants previously untreated Follicular Lymphoma, 10 Marginal Zone Lymphoma

Outcome measures

Outcome measures
Measure	Arm 1 n=48 Participants 38 participants previously untreated Follicular Lymphoma, 10 Marginal Zone Lymphoma
Progression Free Survival (PFS) PFS at 24 months (previously untreated Follicular Lymphoma)	71.2 percentage of participants Interval 57.7 to Not reached
Progression Free Survival (PFS) PFS at 24 months (mzl)	54.2 percentage of participants Interval 25.7 to Not reached

SECONDARY outcome

Timeframe: At 120 weeks

Population: 2 participants were unevaluable

Will be defined as the percentage of participants with a CR at 120 weeks as determined by the principal investigator (Cheson, Lugano classification 2014).

Outcome measures

Outcome measures
Measure	Arm 1 n=46 Participants 38 participants previously untreated Follicular Lymphoma, 10 Marginal Zone Lymphoma
Complete Response (CR) Rate	63 percentage of participant Interval 47.5 to 76.8

SECONDARY outcome

Timeframe: Up to 3 years

Population: 2 participants were unevaluable

Will be defined as the percentage of participants with an ORR and assessed by the investigator based on Cheson, Lugano 2014. The best ORR will be recorded.

Outcome measures

Outcome measures
Measure	Arm 1 n=46 Participants 38 participants previously untreated Follicular Lymphoma, 10 Marginal Zone Lymphoma
Overall Response Rate (ORR) (CR Rate + Partial Response [PR])	95.8 percentage of participants Interval 85.7 to 99.5

SECONDARY outcome

Timeframe: Time by which measurement criteria for CR rate or PR, whichever is recorded first, is met until death or the first date by which progressive disease is documented; assessed up to 71.2 months

Population: 2 participants were unevaluable

Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% CI.

Outcome measures

Outcome measures
Measure	Arm 1 n=46 Participants 38 participants previously untreated Follicular Lymphoma, 10 Marginal Zone Lymphoma
Duration of Response (DOR)	71.2 months Interval 57.7 to Not reached

SECONDARY outcome

Timeframe: From the date of course 1, day 1 to the date of first documented progression, transformation to diffuse large B-cell lymphoma, initiation of new anti-lymphoma treatment, or death; assessed up to 70.2 months

Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% CI.

Outcome measures

Outcome measures
Measure	Arm 1 n=48 Participants 38 participants previously untreated Follicular Lymphoma, 10 Marginal Zone Lymphoma
Event Free Survival (EFS)	70.2 months Interval 53.4 to Not reached

SECONDARY outcome

Timeframe: From the date of course 1, day 1 to the date of first documented administration of any anti-lymphoma treatment (chemotherapy, radiotherapy, immune therapy, radioimmunotherapy, or other experimental therapy); assessed up to 75.8 months

Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% CI.

Outcome measures

Outcome measures
Measure	Arm 1 n=48 Participants 38 participants previously untreated Follicular Lymphoma, 10 Marginal Zone Lymphoma
Time to Next Anti-lymphoma Treatment (TTNT)	75.8 months Interval 70.5 to Not reached

SECONDARY outcome

Timeframe: From the date of course 1, day 1 to the date of death regardless of cause; assessed up to 78 months

Secondary endpoints included best and 120 week complete response rate (CRR) and ORR by Lugano classification, duration of response, event free survival, time to next anti-lymphoma treatment, overall survival (OS) and safety. Response evaluation was performed at cycle 4, day 1, cycle 7 day 1, at the end of cycle 12, then every 12 weeks for the first four assessments, then every 24 weeks until disease progression

Outcome measures

Outcome measures
Measure	Arm 1 n=48 Participants 38 participants previously untreated Follicular Lymphoma, 10 Marginal Zone Lymphoma
Overall Survival (OS) Rate	97.9 percentage of participants

Adverse Events

Arm 1

Serious events: 24 serious events

Other events: 40 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Arm 1 n=48 participants at risk 38 participants previously untreated Follicular Lymphoma, 10 Marginal Zone Lymphoma
Gastrointestinal disorders Diarrhea	12.5% 6/48 • 4 years, 1 month The time a subject has signed and dated an Informed Consent Form (ICF) until completion of the subject's last study-related procedure (which may include contact for follow-up safety).
Respiratory, thoracic and mediastinal disorders Dyspnea	2.1% 1/48 • 4 years, 1 month The time a subject has signed and dated an Informed Consent Form (ICF) until completion of the subject's last study-related procedure (which may include contact for follow-up safety).
Nervous system disorders Fatigue	4.2% 2/48 • 4 years, 1 month The time a subject has signed and dated an Informed Consent Form (ICF) until completion of the subject's last study-related procedure (which may include contact for follow-up safety).
Skin and subcutaneous tissue disorders Pruritis	2.1% 1/48 • 4 years, 1 month The time a subject has signed and dated an Informed Consent Form (ICF) until completion of the subject's last study-related procedure (which may include contact for follow-up safety).
Skin and subcutaneous tissue disorders Rash Maculopapular	50.0% 24/48 • 4 years, 1 month The time a subject has signed and dated an Informed Consent Form (ICF) until completion of the subject's last study-related procedure (which may include contact for follow-up safety).
Blood and lymphatic system disorders Anemia	2.1% 1/48 • 4 years, 1 month The time a subject has signed and dated an Informed Consent Form (ICF) until completion of the subject's last study-related procedure (which may include contact for follow-up safety).
Blood and lymphatic system disorders Leukopenia	4.2% 2/48 • 4 years, 1 month The time a subject has signed and dated an Informed Consent Form (ICF) until completion of the subject's last study-related procedure (which may include contact for follow-up safety).
Blood and lymphatic system disorders Neutropenia	14.6% 7/48 • 4 years, 1 month The time a subject has signed and dated an Informed Consent Form (ICF) until completion of the subject's last study-related procedure (which may include contact for follow-up safety).

Other adverse events

Other adverse events
Measure	Arm 1 n=48 participants at risk 38 participants previously untreated Follicular Lymphoma, 10 Marginal Zone Lymphoma
Musculoskeletal and connective tissue disorders Arthralgia	27.1% 13/48 • 4 years, 1 month The time a subject has signed and dated an Informed Consent Form (ICF) until completion of the subject's last study-related procedure (which may include contact for follow-up safety).
Eye disorders Blurred Vision	10.4% 5/48 • 4 years, 1 month The time a subject has signed and dated an Informed Consent Form (ICF) until completion of the subject's last study-related procedure (which may include contact for follow-up safety).
Infections and infestations Chills	31.2% 15/48 • 4 years, 1 month The time a subject has signed and dated an Informed Consent Form (ICF) until completion of the subject's last study-related procedure (which may include contact for follow-up safety).
Gastrointestinal disorders Constipation	27.1% 13/48 • 4 years, 1 month The time a subject has signed and dated an Informed Consent Form (ICF) until completion of the subject's last study-related procedure (which may include contact for follow-up safety).
Respiratory, thoracic and mediastinal disorders Cough	18.8% 9/48 • 4 years, 1 month The time a subject has signed and dated an Informed Consent Form (ICF) until completion of the subject's last study-related procedure (which may include contact for follow-up safety).
Gastrointestinal disorders Diarrhea	47.9% 23/48 • 4 years, 1 month The time a subject has signed and dated an Informed Consent Form (ICF) until completion of the subject's last study-related procedure (which may include contact for follow-up safety).
Blood and lymphatic system disorders Edema, limbs	37.5% 18/48 • 4 years, 1 month The time a subject has signed and dated an Informed Consent Form (ICF) until completion of the subject's last study-related procedure (which may include contact for follow-up safety).
Nervous system disorders Fatigue	72.9% 35/48 • 4 years, 1 month The time a subject has signed and dated an Informed Consent Form (ICF) until completion of the subject's last study-related procedure (which may include contact for follow-up safety).
Infections and infestations Fever	22.9% 11/48 • 4 years, 1 month The time a subject has signed and dated an Informed Consent Form (ICF) until completion of the subject's last study-related procedure (which may include contact for follow-up safety).
General disorders Headache	35.4% 17/48 • 4 years, 1 month The time a subject has signed and dated an Informed Consent Form (ICF) until completion of the subject's last study-related procedure (which may include contact for follow-up safety).
Gastrointestinal disorders Mucositis	25.0% 12/48 • 4 years, 1 month The time a subject has signed and dated an Informed Consent Form (ICF) until completion of the subject's last study-related procedure (which may include contact for follow-up safety).
Nervous system disorders Myalgia	77.1% 37/48 • 4 years, 1 month The time a subject has signed and dated an Informed Consent Form (ICF) until completion of the subject's last study-related procedure (which may include contact for follow-up safety).
Gastrointestinal disorders Nausea	33.3% 16/48 • 4 years, 1 month The time a subject has signed and dated an Informed Consent Form (ICF) until completion of the subject's last study-related procedure (which may include contact for follow-up safety).
Nervous system disorders Numbness	14.6% 7/48 • 4 years, 1 month The time a subject has signed and dated an Informed Consent Form (ICF) until completion of the subject's last study-related procedure (which may include contact for follow-up safety).
Skin and subcutaneous tissue disorders Pruritis	14.6% 7/48 • 4 years, 1 month The time a subject has signed and dated an Informed Consent Form (ICF) until completion of the subject's last study-related procedure (which may include contact for follow-up safety).
Skin and subcutaneous tissue disorders Rash Maculopapular	33.3% 16/48 • 4 years, 1 month The time a subject has signed and dated an Informed Consent Form (ICF) until completion of the subject's last study-related procedure (which may include contact for follow-up safety).
Gastrointestinal disorders Vomiting	10.4% 5/48 • 4 years, 1 month The time a subject has signed and dated an Informed Consent Form (ICF) until completion of the subject's last study-related procedure (which may include contact for follow-up safety).
Blood and lymphatic system disorders Anemia	8.3% 4/48 • 4 years, 1 month The time a subject has signed and dated an Informed Consent Form (ICF) until completion of the subject's last study-related procedure (which may include contact for follow-up safety).
Blood and lymphatic system disorders Leukopenia	0.00% 0/48 • 4 years, 1 month The time a subject has signed and dated an Informed Consent Form (ICF) until completion of the subject's last study-related procedure (which may include contact for follow-up safety).
Blood and lymphatic system disorders Neutropenia	6.2% 3/48 • 4 years, 1 month The time a subject has signed and dated an Informed Consent Form (ICF) until completion of the subject's last study-related procedure (which may include contact for follow-up safety).

Additional Information

Loretta Nastoupil, MD

The University of Texas MD Anderson Cancer Center

Phone: (713) 792-2860

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place