Lenalidomide and Idelalisib in Treating Patients With Recurrent Follicular Lymphoma

NCT ID: NCT01644799

Last Updated: 2018-01-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-07-31
• Study Completion Date: 2017-05-31

Brief Summary

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.

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.

Conditions

Recurrent Follicular Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

idelalisib

Intervention Type: DRUG

oral

lenalidomide

Intervention Type: DRUG

oral

Interventions

idelalisib

oral

Intervention Type: DRUG

lenalidomide

oral

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Gilead Sciences

INDUSTRY

Sponsor Role: collaborator

Celgene Corporation

INDUSTRY

Sponsor Role: collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John P. Leonard, MD

Role: PRINCIPAL_INVESTIGATOR

Weill Medical College of Cornell University

Locations

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, United States

University of Chicago

Chicago, Illinois, United States

Washington University School of Medicine

St Louis, Missouri, United States

Weill Medical College of Cornell University

New York, New York, United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Ohio State University Medical Center

Columbus, Ohio, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 28314699 (View on PubMed)

Other Identifiers

CDR0000736814

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2012-01988

Identifier Type: REGISTRY

Identifier Source: secondary_id

U10CA031946

Identifier Type: NIH

Identifier Source: secondary_id

View Link

A051202

Identifier Type: -

Identifier Source: org_study_id