Lenalidomide Maintenance Therapy After High Dose BEAM With or Without Rituximab

PRIMARY OBJECTIVES:

I. To establish the maximum tolerated dose (MTD) of Lenalidomide given in the post transplant
setting for a 12 month maintenance period.

SECONDARY OBJECTIVES:

I. To obtain preliminary estimates of the 1-year response rate, event-free and overall
survival using this regimen.

OUTLINE: This is a phase I dose escalation study of lenalidomide followed by a phase II
study.

PRE-CONDITIONING (patients with CD20+ non-Hodgkin lymphoma): Patients receive rituximab
intravenously (IV) per standard of care.

PREPARATIVE REGIMEN: Patients receive carmustine IV on day -6, etoposide IV twice daily (BID)
and cytarabine IV BID on days -5 through -2, and melphalan IV on day -1.

AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION: Patients undergo stem cell infusion on
day 0.

MAINTENANCE THERAPY: Beginning approximately 100 days post-transplant, patients receive
lenalidomide orally (PO) on days 1-21. Treatment repeats every 28 days for 12 courses in the
absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Inclusion Criteria:

- Persistent, or relapsed non-Hodgkin's lymphoma (NHL) (any histology) that is
chemo-resistant (< a partial response [PR]), patients who have received >= 3 prior
chemotherapy regimens, or patients with lymphomas that have a high relapse rate
following autologous or syngeneic stem cell transplantation (transformed NHL,
peripheral T-cell lymphoma [PTCL], mantle cell lymphoma [MCL], anaplastic lymphoma
kinase [ALK]-negative anaplastic large cell lymphoma [ALCL, alk neg]), or patients
with a positive positron emission tomography (PET) scan prior to transplant, and
otherwise eligible for transplantation with adequate end-organ function

- Patients that relapse within one year of diagnosis

- Able to collect >= 1.5 x 10^6 CD34+/kg cell for transplantation

- Absolute neutrophil count (ANC) >= 1000 cells/mm^3 and platelet count >= 60 mm^3 when
maintenance Lenalidomide is started (day 100 [+/- 7 days] post-transplant)

- Patients must be willing to give written informed consent, and sign an institutionally
approved consent form before performance of any study-related procedure not part of
normal medical care, with the understanding that consent may be withdrawn by the
subject at any time without prejudice to future medical care

- Able to adhere to the study visit schedule and other protocol requirements

- Expected survival duration of >= six months

- Karnofsky Performance Status >= 70

- Liver functions =< 2 x upper limits of normal (ULN) unless due to lymphoma or due to
Gilberts disease

- Serum creatinine < 2.0 mg/dL or calculated creatinine clearance > 50ml/min

- Patients > age 60 or with clinical signs of heart disease must have ejection fraction
>= 45% left ventricular ejection fraction (LVEF)

- Patients with clinical signs of pulmonary insufficiency must have diffusion capacity
of the lung for carbon monoxide (DLCO) to be measured at >= 50% of predicted value

- No serious disease or condition that, in the opinion of the investigator, would
compromise the patient's ability to participate in the study

- Disease free of prior malignancies for >= 2 years with exception of currently treated
basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix
or breast or low risk prostate cancer after curative therapy

- All study participants must be registered into the mandatory RevAssist program, and be
willing and able to comply with the requirements of RevAssist

- Females of childbearing potential (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 and again
within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7
days)

- 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 she starts
taking lenalidomide

- FCBP must also agree to ongoing pregnancy testing

- Men must agree to use a latex condom during sexual contact with a FCBP even if they
have had a successful vasectomy

- Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients
intolerant to acetylsalicylic acid [ASA] may use warfarin or low molecular weight
heparin)

- Male subject agrees to use an acceptable method for contraception for the duration of
the study

Exclusion Criteria:

- Chemosensitive NHL, except patients receiving >= 3 prior chemotherapy regimens, or
patients having transformed NHL, PTCL, MCL or ALCL, alk neg

- End-organ function not appropriate for transplantation

- Inability to collect adequate stem cells

- Known positive for human immunodeficiency virus (HIV) or infectious hepatitis, type A,
B or C or active Hepatitis

- Any serious medical condition, laboratory abnormality, or psychiatric illness that
would prevent the subject from signing the informed consent form

- Pregnant or breast feeding females (lactating females must agree not to breast feed
while taking lenalidomide)

- Known hypersensitivity to thalidomide

- The development of erythema nodosum if characterized by a desquamating rash while
taking thalidomide or similar drugs

- Any prior use of lenalidomide

- Concurrent use of other anti-cancer agents or treatments

- Serum creatinine >= 2.0mg/dL or calculated creatinine clearance =< 50ml/min

- Total bilirubin >= 2 times upper limits of normal (unless due to Gilberts disease or
NHL)

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >= 4 times the
upper limits of normal

- Active infection at the start of Lenalidomide

- Myocardial infarction within 6 months prior to enrollment or has New York Heart
Association (NYHA) Class III or IV heart failure uncontrolled angina, severe
uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
ischemia or active conduction system abnormalities

- Prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be
documented by the investigator as not medically relevant

- History of life threatening or recurrent thrombosis/embolism; patients may participate
if they are adequately anticoagulated during the treatment

- Patient has > Grade 2 peripheral neuropathy within 14 days before enrollment