Lenalidomide and Idelalisib in Treating Patients With Recurrent Follicular Lymphoma

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.

- 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