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

Phase 2
18 Years
65 Years
Open (Enrolling)
Multiple Myeloma

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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who fails to collect a minimum of 4 x 106/kg CD 34+ will be withdrawn from the study.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

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.

Inclusion Criteria:

1. Newly diagnosed multiple myeloma patients with an HLA identical sibling suitable for
PBSC donation and treated in induction with thalidomide or bortezomib or lenalidomide
conteining regimes.

2. Complete cytogenetic analysis at diagnosis, including FISH analysis for chromosome
deletions 13 and 17, and translocations (4;14) (11;14) and (14;16).

3. The patient must have the capacity to give informed consent.

4. Age >18 and < 65

5. If female, the patient is either postmenopausal since at least 24 consecutive months
or surgically sterilized or she agrees to practice sexual abstinence or to use two
reliable methods for contraception (e.g. a hormonal contraceptive, intra-uterine
device, diaphragm with spermicide, condom with spermicide) for the duration of study

6. If male, the patient agrees to practice sexual abstinence or to use a latex condom
during any sexual contact with women of childbearing potential for the duration of

7. Negative pregnancy test

Exclusion Criteria:

1. Karnofsky score less than 60 (see appendix C), unless due solely to myeloma

2. Left ventricular ejection fraction less than 40%, or symptomatic coronary artery
disease or other cardiac failure requiring therapy

3. Bilirubin greater than 2 X the upper limit of normal, or SGPT and SGOT > 4 X the
upper limit of normal

4. DLCO < 40% (corrected) or receiving continuous supplemental oxygen.

5. Creatinine clearance < 40 cc/min at the time of initial autografting evaluation.

6. Patients with poorly controlled hypertension

7. Patients with active non-hematologic malignancies (except non-melanoma skin cancers).

8. Patients with a history of non-hematologic malignancies (except non-melanoma skin
cancers) currently in a complete remission, who are less than 5 years from the time
of complete remission, and have a >20% risk of disease recurrence

9. Seropositive for HIV

10. Fertile men or women unwilling to use contraceptive techniques during and for 12
months following treatment.

11. To evaluate toxicity and tolerability of lenalidomide after allografting

12. To evaluate efficacy of lenalidomide in inducing complete remission 12 months after

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Lenalidomide toxicity and tolerability after allografting

Outcome Description:

To evaluate toxicity and tolerability of lenalidomide after allografting.

Outcome Time Frame:

6 years

Safety Issue:


Principal Investigator

Benedetto Bruno, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Division of Hematology - University of Torino - A.O.U. San Giovanni Battista - Torino - Italy


Italy: Ministry of Health

Study ID:




Start Date:

September 2008

Completion Date:

December 2014

Related Keywords:

  • Multiple Myeloma
  • Lenalidomide
  • Tandem Autologous-Allogeneic Transplant
  • Multiple Myeloma
  • Neoplasms, Plasma Cell