Trial Information

Safety And Efficacy Of Lenalidomide As Maintenance Therapy In Patients With Newly Diagnosed Multiple Myeloma Following A Tandem Autologous-Allogeneic Transplant

A. Pre-transplant phase: Induction Therapy

Patients will start induction treatment with lenalidomide and dexamethasone (RD) for 4
cycles every 28 days (as was detailed also in the GIMEMA protocol RV-MM-PI-209):

- Lenalidomide will be given orally at the dose of 25 mg/day for 21 days followed by a 7
day rest period (day 22 to 28),

- Dexamethasone will be given orally at the dose of 40 mg on days 1, 8, 15 and 22 every
28 days.

If a patient relapses during RD before the end of the 4th cycle, the induction treatment may
be held and stem cell collection may be attempted with cyclophosphamide according to
physician willing.

For dose reduction during induction therapy see Appendix O. Antithrombotic prophylaxis as
per protocol RV-MM-PI-209. For patients not previously enrolled in protocol RV-MM-PI-209, we
recommend prophylaxes with aspirin for patients without additional thrombotic risk factors,
and low molecular weight heparin (LMWH) 100 U/kg for the others.

Otherwise, induction schemas are accepted provided thalidomide, lenalidomide or bortezomib,
alone or in combination, are included.

B. Peripheral Blood Stem Cell (PBSC) Mobilization and collection

After 1-2 months from the completion of the last induction course, patients will undergo
PBSC mobilization with cyclophosphamide 4 g/m2 and G-CSF (10 ug/kg/day starting at day 5
until completion of PBSC collection) to collect an adequate number of PBSC (4 to 10 x
106/kg CD 34+ cells). Patients who fail to collect the minimum of 4 x 106/kg CD 34+ cells
will receive a second course of cyclophosphamide for a second mobilization attempt. Patients
who fails to collect a minimum of 4 x 106/kg CD 34+ will be withdrawn from the study.

C. High-Dose Melphalan / Autologous PBSC Transplant

High dose melphalan will be given 4 to 8 weeks after high dose cyclophosphamide.

1. Melphalan will be administered at a cumulative dose of 200 mg/m2. This will be given in
one dose infused on day -2. Dose will be calculated according to the participating
institutional standard practice for using body weight. High dose Melphalan is
administered via a central catheter as per single center procedure.

2. Peripheral Blood Stem Cell or Bone Marrow Infusion: Infuse > 2 x 106 CD 34+ cells /kg,
hydration requirements, and pre-medication per guidelines of the institution.

3. G-CSF: Administer G-CSF 5 ug/kg/day subcutaneously or intravenously from day +3 until
ANC >1000 for 3 days.

D. Allogeneic transplant phase: Non-myeloablative PBSC Allografting

Pre-conditioning Upon recovery from high-dose melphalan, between 40-120 days post
autografting (preferably within 60 days) patients will proceed to nonmyeloablative
allograft. If indicated, radiation to high risk skeletal lesions may be given
pre-transplant. If interval exceeds 120 days, present to PCC for discussion and approval.

Recovery from high-dose melphalan will be defined by patients achieving the following
clinical criteria after receiving high dose melphalan:

1. mucositis and gastrointestinal symptoms resolved, off hyperalimentation and intravenous
hydration;

2. have completed steroids for autologous GVHD;

3. LFT / renal function values within the inclusion criteria for initial autograft;

4. off IV antibiotics and amphotericin for documented infections;

5. patients should be CMV antigenemia negative;

6. if patients have experienced CMV infection post-autograft, they must have completed
therapy with Ganciclovir or Foscarnet and have been off this therapy for > two weeks
and remain CMV antigenemia negative;

7. should have completed administration of any radiotherapy;

8. any patient who does not fulfill these criteria, can be discussed with the principle
investigator for recommendations as to the timing of the allograft.