Lenalidomide and Idelalisib in Treating Patients With Recurrent Follicular Lymphoma

A Phase I Trial of Lenalidomide and Idelalisib in Recurrent Follicular Lymphoma

Biologic therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Idelalisib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. This phase I trial studies the side effects and the best dose of lenalidomide when giving together with idelalisib in treating patients with recurrent follicular lymphoma.

Study Overview

• Status: Completed
• Conditions: Recurrent Follicular Lymphoma
• Intervention / Treatment: Drug: idelalisib; Drug: lenalidomide

Detailed Description

OUTLINE:

This is a multicenter, dose-escalation study of lenalidomide.

Patients receive lenalidomide orally (PO) on days 1-21 and idelalisib twice daily (BID) on days 1-28. Treatment with lenalidomide and idelalisib repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. The primary and secondary objectives of the study include the following:

Primary Objective:

• To determine the maximum-tolerated dose (MTD) of lenalidomide when combined with idelalisib in patients with recurrent follicular non-Hodgkin lymphoma (NHL).

Secondary Objectives:

• To determine the toxicity profile of lenalidomide and idelalisib therapy in patients with recurrent follicular NHL
• To estimate the efficacy (overall response rate [ORR], complete response rate [CRR], and progression-free survival [PFS]) of lenalidomide and idelalisib in patients with recurrent follicular NHL in a preliminary fashion (using a small extension cohort)
• To assess whether the therapeutic effects of the lenalidomide and idelalisib combination are sufficiently promising to warrant evaluation in a subsequent (phase II/III) randomized trial

After completion of study treatment, patients are followed at 2, 4, 6, 9, 12, 15, 18, and 24 months and then annually. Patients are followed once every year for a maximum of 10 years from study entry.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • MedStar Georgetown University Hospital
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • New York, New York, United States, 10065
      • Weill Medical College of Cornell University
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

• Documentation of Disease

  • Previously treated, histologically confirmed follicle center cell lymphoma, World Health Organization (WHO) classification grade 1, 2, or 3a (> 15 centroblasts per high-power field with centrocytes present)
  • Bone marrow biopsies as the sole means of diagnosis are not acceptable; fine-needle aspirates are not acceptable for diagnosis
  • Confirmed Cluster of Differentiation 20 (CD20) antigen expression by flow cytometry or immunohistochemistry
• Measurable disease must be > 1 cm

• Prior treatment

  • Patient must have had prior treatment with rituximab either alone or in combination with chemotherapy.
  • Last prior treatment regimen need not include rituximab.
  • Patient must have a time to progression of ≥ 6 months from last rituximab dose of last rituximab containing regimen.
  • No corticosteroids within two weeks prior to study, except for maintenance therapy for a non-malignant disease; maintenance therapy dose may not exceed 20 mg/day prednisone or equivalent
• Patients must be 18 years of age or older.

• Human immunodeficiency virus (HIV) Infection

  • Patients with HIV infection are eligible, provided they meet the following:
  • CD4+ cell count > 350/mm^3
  • Treatment sensitive HIV and, if on anti-HIV therapy, HIV viral load < 50 copies/mm^3
  • No history of Acquired Immunodeficiency Syndrome (AIDS)-defining conditions or other HIV related illness
  • No concurrent zidovudine or stavudine because of overlapping toxicities with protocol therapy
• Patients must not have known central nervous system (CNS) involvement
• Patients must not have known positivity for hepatitis B, as evidenced by + HBsAG or anti-HBc and must not have known history of hepatitis C
• Patients must not have any currently active secondary malignancy except non-melanoma skin cancer. Patients are not considered to have a "currently active" secondary malignancy if they have completed anticancer therapy and are deemed to have < 30% risk of relapse by their physician.
• Patients must not have had deep vein thrombosis or pulmonary embolism within the past 3 months.
• Patients must not have had radioimmunotherapy within 12 months of study entry.
• Patients must not have other concurrent investigational or commercial agents or therapies for lymphoma.
• Patients must not have current dialysis treatment.

• Patients must be non-pregnant and non-nursing.

  • Females of Child Bearing Potential (FCBP) is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally postmenopausal for at least 24 consecutive months (eg, has had menses at any time preceding 24 consecutive months)
  • FCBP must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10-14 days prior to registration

  • FCBP must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control

    • One highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before starting lenalidomide
    • FCBP must also agree to ongoing pregnancy testing
  • Men must agree to use a latex condom during sexual contact with a female of childbearing potential, even if they have had a successful vasectomy

• CYP3A4 Strong Inducers and Inhibitors

  • Patients must not be on strong CYP3A4 inhibitors and/or inducers.
  • Strong inhibitors are prohibited: indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, ketoconazole, nefazodone
  • Strong inducers are prohibited: carbamazepine, phenobarbital, phenytoin, pioglitazone, rifabutin, rifampin, St. John's Wort, troglitazone

• Required Initial Laboratory Values

  • Absolute neutrophil count (ANC) ≥ 1,000 mm³
  • Total Bilirubin ≤ 2 times upper limit of normal (ULN) (unless due to Gilbert disease or lymphoma)
  • Creatinine ≤ 1.5 times ULN (unless due to lymphoma) OR creatinine clearance (CrCl) ≤ 60 mL/minute
  • Platelet count ≥ 75,000 mm³
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2 x ULN

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: lenalidomide and idelalisib; Lenalidomide: Lenalidomide will be administered orally on days 1-21 followed by 7 days of rest, every 28 days. A treatment cycle will be considered 28 days in length. In the absence of intolerable toxicity or disease progression, lenalidomide will be given for a total of 12 cycles. Idelalisib: Dosing is fixed in all cohorts receiving idelalisib at 150 mg orally (twice daily) for 12 cycles, with the exception of dose modifications for toxicity.

Drug: idelalisib; oral; Drug: lenalidomide; oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
MTD based on the incidence of dose-limiting toxicity (DLT) assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0	Up to 13 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Toxicity profile assessed by NCI CTCAE version 4.0	Up to 10 years
OR rate assessed up to 10 years	Up to 10 years
CR rate assessed up to 10 years	Up to 10 years
PFS assessed up to 10 years	Up to 10 years

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI); Gilead Sciences; Celgene Corporation
• Investigators: Principal Investigator: John P. Leonard, MD, Weill Medical College of Cornell University

Publications and helpful links

General Publications

• Smith SM, Pitcher BN, Jung SH, Bartlett NL, Wagner-Johnston N, Park SI, Richards KL, Cashen AF, Jaslowski A, Smith SE, Cheson BD, Hsi E, Leonard JP. Safety and tolerability of idelalisib, lenalidomide, and rituximab in relapsed and refractory lymphoma: the Alliance for Clinical Trials in Oncology A051201 and A051202 phase 1 trials. Lancet Haematol. 2017 Apr;4(4):e176-e182. doi: 10.1016/S2352-3026(17)30028-5. Epub 2017 Mar 15.

Study record dates

Study Major Dates

• Study Start (Actual): August 2, 2013
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): May 1, 2017

Study Registration Dates

• First Submitted: July 17, 2012
• First Submitted That Met QC Criteria: July 17, 2012
• First Posted (Estimated): July 19, 2012

Study Record Updates

• Last Update Posted (Actual): June 16, 2026
• Last Update Submitted That Met QC Criteria: June 15, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: recurrent grade 3 follicular lymphoma; recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Hemic and Lymphatic Diseases; Lymphoma, Follicular; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Carboxylic Acids; Piperidines; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Isoindoles; Lenalidomide; idelalisib
• Other Study ID Numbers: A051202; U10CA031946 (U.S. NIH Grant/Contract); CDR0000736814 (Registry Identifier: PDQ (Physician Data Query)); NCI-2012-01988 (Registry Identifier: CTRP (Clinical Trials Reporting System))