Thalidomide to Overcome Lenalidomide Resistance After Autologous Hematopoietic Stem Cell Transplantation (HCT)

Study Drug Administration:

If you are found to be eligible to take part in this study, you will begin taking
lenalidomide and thalidomide by mouth once a day, in the evening. Thalidomide should be taken
at least 1 hour after your evening meal. Bedtime is the best time to take thalidomide.

Swallow the lenalidomide and thalidomide capsules whole with at least 4 ounces of water. Do
not open, crush, or break the lenalidomide or thalidomide capsules. If you touch a broken
lenalidomide or thalidomide capsule, wash the affected area of your body with soap and water.

If you miss a dose of lenalidomide and/or thalidomide, and it has been less than 12 hours
since your regular dosing time, take it as soon as you remember. If it has been more than 12
hours, just skip your missed dose. Do not take 2 doses at the same time.

If you take too much lenalidomide and/or thalidomide (overdose), call your primary healthcare
provider or poison control center right away.

If you vomit after taking your dose, you should wait to take another dose until the next
scheduled time.

You will be given a patient study drug diary. You will use this diary to write down what time
you took each dose of lenalidomide and thalidomide. You need to bring the study drug diary to
every study visit so the study staff can review it.

Since lenalidomide and thalidomide both increase the risk of developing blood clots,
especially in patients who are at high risk or with a history of blood clots, you may receive
heparin, warfarin, or aspirin to help prevent blood clots. Your doctor will decide which
medication you need, or your doctor may decide that you do not need a medication to help
prevent blood clots, based on your platelet count (cells that help your blood clot).

You will be given standard drugs to help decrease the risk of side effects. You may ask the
study staff for information about how the drugs are given and their risks.

Study Visits:

Once a month for the first 6 months:

- You will have a physical exam.

- You will have a neurological exam (tests to check the functioning of your nerves,
including tests of your balance and reflexes). You will be asked about any numbness or
tingling you may be experiencing.

- Blood (about 2 tablespoons) and urine will be collected for routine tests, liver and
kidney function tests, blood clotting tests (if needed), and tests to check the status
of the disease.

If the doctor thinks the disease has either gone into remission (gotten better) or has gotten
worse, you will have additional blood tests and a bone marrow biopsy to check the status of
the disease.

After Month 6, during every even-numbered month you are on study (Months 8, 10, 12, and so
on), blood (about 2 tablespoons) and urine will be collected for routine tests and to check
the status of the disease.

Questionnaires:

You will be asked to complete a questionnaire about your symptoms and quality of life during
screening, once a month for the first 6 months, and then every other month while you are on
study.

You will sometimes fill out the questionnaire by hand on a piece of paper, or you may be
asked the questions over the telephone by a member of the study staff. Other times, the
questionnaire will be done over the phone with an automated phone system. The telephone
system will ask you to rate how strong and tolerable the symptoms are, and how much the
symptoms interfere with your daily life. Rating your symptoms using the telephone system
should take less than 5 minutes for each call. The research nurse will teach you how to use
the automated telephone system.

Length of Treatment:

You will receive the study drugs for up to 2 years. You will no longer be able to take the
study drug if the doctor thinks it is in your best interest, if the disease gets worse, if
intolerable side effects occur, or if you are unable to follow study directions or keep
appointments.

Your participation on the study will be over after the end-of-study visit.

End-of-Study Visit:

About 30 days of your last dose of study drugs:

- You will have a physical exam and neurological exam.

- Blood (about 2 tablespoons) and urine will be collected for routine tests and to check
the status of the disease.

- You will have a bone marrow biopsy to check the status of the disease, if your doctor
thinks it is needed.

This is an investigational study. Lenalidomide and Thalidomide are FDA approved and
commercially available for the treatment of myeloma. The use of these chemotherapy drugs in
treating MM that has gotten worse after treatment with lenalidomide is considered
investigational. The study doctor can explain how the study drug(s) are designed to work.

Up to 17 patients will take part in this study. All will be enrolled at MD Anderson.

Inclusion Criteria:

1. Patient or legally authorized representative able to sign an informed consent form.

2. Age 18 years old or older.

3. Multiple myeloma showing signs of biochemical progression while taking lenalidomide or
lenalidomide plus dexamethasone maintenance therapy after autologous hematopoietic
stem cell transplantation. (Progression is defined solely based on serum or urine
M-protein, or in patients without measurable serum and urine M-protein levels; the
difference between involved and uninvolved serum free light chain level -- please also
see appendix E for full details.)

4. Patients with biochemical progression only with at least >/= 25% increase from the
baseline in any of the following parameters on at least 2 occasions; and when the
treating physician deems a change in therapy is necessary: a. Serum M-protein; b.
Urine M-protein; or, c. In patients without measureable serum and urine M-protein
levels; the difference between involved and uninvolved free light chain levels.

5. Lenalidomide must have been used for at least 6 months after autologous hematopoietic
stem cell transplantation with the current dose of Lenalidomide 15 mg/day or less.

6. Serum creatinine clearance (Cockcroft-Gault Equation) >= 50 mL/minute.

7. Performance score of at least 80% by Karnofsky or 0 to 2 Eastern Cooperative Oncology
Group (ECOG).

8. Patients must be informed of the Celgene Risk Management Program and mandatory
registration as well as be willing and able to comply with its requirements.

9. Negative Beta Human Chorionic Gonadotropin (HCG) test in a woman with child bearing
potential defined as not post-menopausal for 12 months or no previous surgical
sterilization and willing to ongoing pregnancy testing while on treatment with
lenalidomide.

10. Woman with child bearing potential 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.

11. Men must agree to use a latex condom during sexual contact with females of child
bearing potential even if they have had a successful vasectomy.

12. Laboratory test results within these ranges: a. Absolute neutrophil count > 1000
cells/mm3. b. Platelet count > 50,000 cells/mm3 for patients with < 50% of bone marrow
plasma cells OR platelet count > 25,000 cells/mm3 for patients in whom > 50% of the
bone marrow nucleated cells were plasma cells. c. Total bilirubin AST (SGOT) and ALT (AGPT)
13. Able to take anticoagulation, warfarin or equivalent agent, as detailed in the
treatment plan.

14. HIV negative.

Exclusion Criteria:

1. Any serious medical condition or psychiatric illness that would prevent the subject
from signing the informed consent form.

2. Patients with symptomatic relapse, including those with new bone lesions, soft tissue
plasmacytomas, an increase in the size of existing bone lesions or soft tissue
plasmacytomas, decrease in hemoglobin, rise in serum creatinine or hypercalcemia.

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

4. Known hypersensitivity to thalidomide or lenalidomide.

5. Known history of resistance to Thalidomide.

6. Patients with grade III-IV neuropathy.