Phae I/II Study of Lenalidomide in Combination With Rituximab, Ifosfamide, Etoposide, and Carboplatin (RICER) as Salvage Therapy With Single Agent Lenalidomide as Maintenance Therapy Post-Autologous Stem Cell Transplantation for the Treatment of Diffuse Large B-Cell Lymphoma (DLBCL) Patients in First Relapse

Inclusion Criteria:

Understand and voluntarily sign an informed consent form.

1. Age 18 years at the time of signing the informed consent form.

2. Able to adhere to the study visit schedule and other protocol requirements.

3. Histologically confirmed diffuse large B cell lymphoma

4. Relapsed or refractory after one prior therapeutic treatment for DLBCL. Refractory is
defined as patients received adequate prior treatment and did not respond during
treatment or progressed within 90 days of last treatment.

5. Measurable disease with at least on bidimensional lymph node or tumor mass >1.5 cm in
the longest diameter that can be followed for response as a target lesion as measured
by PET or CT

6. Histologically confirmed involvement of the bone marrow by DLBCL on the bone marrow
biopsy without other measurable disease

7. Eligible for autologous stem cell transplant

8. All previous cancer therapy, including radiation, hormonal therapy and surgery, must
have been discontinued at least two weeks prior to treatment in this study.

9. ECOG performance status of 2 at study entry (see Appendix B).

10. Laboratory test results within these ranges:

- Absolute neutrophil count >1000 /mm³

- Platelet count > 50,000/mm³ (unless bone marrow is heavily infiltrated with
underlying disease (50% or more) Calculated creatinine clearance of ≥ 60 mL/min
by Cockroft-Gault formula (Appendix E) for patients enrolled into the phase I
portion of the study (Stage I). Calculated creatinine clearance of ≥ 30 mL/min
by Cockroft-Gault formula for patients enrolled into the phase II portion of the
study (Stage II). See Section 5.4.2 for lenalidomide dose adjustment for
calculated creatinine clearance > 30ml/min and < 60ml/min.

- Total bilirubin < 1.5 x ULN.

- AST (SGOT) and ALT (SGPT) < 3 x ULN.

11. Disease free of prior malignancies for > 5 years with exception of currently treated
basal cell, squamous cell carcinoma of the skin, or carcinoma "insitu" of the cervix
or breast.

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

13. 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 starting lenalidomide and 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. All
patients must be counseled at a minimum of every 28 days about pregnancy precautions
and risks of fetal exposure. See Appendix A: Risks of Fetal Exposure, Pregnancy
Testing Guidelines and Acceptable Birth Control Methods.

14. Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients
intolerant to ASA may use warfarin or low molecular weight heparin).

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

1. Pregnant or breast feeding females. (Lactating females must agree not to breast feed
while taking lenalidomide).

2. Any condition, including the presence of laboratory abnormalities, which places the
subject at unacceptable risk if he/she were to participate in the study or confounds
the ability to interpret data from the study.

3. Evidence of laboratory TLS by Cairo-Bishop Definition of Tumor Lysis Syndrome.
Subjects may be enrolled upon correction of electrolyte abnormalities.

4. Use of any other experimental drug or therapy within 28 days of baseline.

5. Known hypersensitivity to thalidomide.

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

7. Concurrent use of other nonprotocol anti-cancer agents or treatments.

8. Known positive for HIV or active infectious hepatitis, type B or C.

9. Refusal of autologous stem cell transplant.

10. Patients with active central nervous system involvement based on clinical evaluation.
Previously treated CNS involvement that has remained asymptomatic for more than
ninety days is allowed if no active CNS disease present as confirmed by MRI or/and
lumbar puncture.

11. Concurrent uncontrolled serious medical ort psychiatric conditions likely to
interfere with participation in this clinical study, as judged by investigator.

12. Prior Lenalidomide exposure for more than 28 days.

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