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A Randomized Phase II Dose Finding Study of Revlimid™ and Melphalan in Patients With Previously Untreated Multiple Myeloma

Phase 2
18 Years
Not Enrolling
Multiple Myeloma and Plasma Cell Neoplasm

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Trial Information

A Randomized Phase II Dose Finding Study of Revlimid™ and Melphalan in Patients With Previously Untreated Multiple Myeloma



- Evaluate the tolerability of 2 different doses of lenalidomide when administered with
melphalan in patients with previously untreated multiple myeloma who are not planning
to undergo future autologous stem cell transplantation.


- Characterize the toxicity profile of lenalidomide in combination with melphalan.

- Determine tumor response in these patients after 2 and 12 courses of induction therapy
with lenalidomide and melphalan and after 6 months of maintenance therapy with

- Determine progression-free and overall survival of these patients.

- Determine time to dose modification and time to dose discontinuation in these patients.


- Examine wnt pathway inhibition in response to lenalidomide on pre- and post-treatment
bone marrow and blood samples using enzyme-linked immunosorbent assay (ELISA), gene
expression profiling, drosophila-based chemical genetics, and surface-enhanced laser
desorption/ionization mass spectrometry (SELDI MS) proteomics.

OUTLINE: This is a multicenter, randomized, open-label, dose-finding study of lenalidomide.

Prior to randomization, 6 patients receive oral lenalidomide at a lower dose (same dose to
be used in arm I) once daily on days 1-21 and oral melphalan once daily on days 1-4.
Treatment repeats every 28 days for 3 courses. If no unacceptable toxicity occurs, the trial
will proceed and randomization will occur.

- Induction therapy: Patients are randomized to 1 of 2 dose levels of lenalidomide.

- Arm I: Patients receive oral lenalidomide once daily on days 1-21 and oral
melphalan once daily on days 1-4.

- Arm II: Patients receive oral lenalidomide as in arm I, but at a lower dose, and
melphalan as in arm I, but at a higher dose.

Treatment in both arms repeats every 28 days for up to 12 courses in the absence of disease
progression or unacceptable toxicity. After 12 courses of induction therapy, patients in
both arms without progressive disease proceed to maintenance therapy.

- Maintenance therapy: Patients receive oral dexamethasone once daily on days 1-4.
Courses repeat every 28 days in the absence of disease progression or unacceptable

After completion of study treatment, patients are followed at 4 weeks and then every 2
months thereafter.

PROJECTED ACCRUAL: A total of 92 patients will be accrued for this study.

Inclusion Criteria


- Histologically confirmed multiple myeloma by one of the following:

- Biopsy of an osteolytic lesion or soft tissue tumor composed of plasma cells

- Bone marrow aspirate and/or biopsy demonstrating ≥ 10% plasmacytosis

- Bone marrow < 10% plasma cells but with ≥ 1 bony lesion AND meets the M-protein

- Ineligible for stem cell transplantation due to any of the following:

- Advanced age

- Comorbid illness

- Patient preference

- Previously untreated disease

- Measurable (i.e., quantifiable) serum M-component of IgG, IgA, IgD, or IgE at initial
diagnosis OR, if only light-chain disease is present (urine M-protein only), urinary
excretion of light-chain protein (Bence Jones) ≥ 1.0 g/24 hours at initial diagnosis

- No nonsecretory myeloma


- ECOG performance status 0-2

- Life expectancy ≥ 12 months

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 150,000/mm^3

- Creatinine ≤ 3 times upper limit of normal (ULN)

- Bilirubin ≤ 1.5 times ULN

- AST and/or ALT ≤ 1.5 times ULN

- Alkaline phosphatase ≤ 1.5 times ULN

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use 2 methods of effective contraception during and for 4 weeks
after completion of study treatment

- No other malignancies within the past 5 years, except adequately treated nonmelanoma
skin cancer or curatively treated in situ cancer of the cervix

- No hypersensitivity to thalidomide or its components, including the development of a
desquamating rash

- No other serious illness or medical condition that would preclude study participation

- No history of significant neurologic or psychiatric disorder that would preclude
informed consent

- No known HIV positivity

- No pre-existing cardiovascular conditions and/or symptomatic cardiac dysfunction,
including any of the following:

- Significant cardiac event (including symptomatic heart failure or angina) within
3 months prior to randomization

- Any cardiac disease that increases risk for ventricular arrhythmia

- History of ventricular arrhythmia that was symptomatic or required treatment,
including any of the following:

- Multifocal premature ventricular contractions

- Bigeminy

- Trigeminy

- Ventricular tachycardia/fibrillation/flutter/arrhythmia NOS


- No prior chemotherapy or corticosteroids for the treatment of multiple myeloma

- Prior corticosteroids for the treatment of hypercalcemia or spinal cord
compression allowed provided maximum levels have not been reached (i.e.,< 120 mg
for dexamethasone or < 792 mg for prednisone)

- Prior radiotherapy to single sites for pain control or local plasmacytoma allowed

- Prior or concurrent bisphosphonates allowed

- At least 28 days since prior investigational anticancer agents or therapy

- No concurrent corticosteroids above physiologic replacement doses

- Concurrent radiotherapy to sites of active myeloma with pain or neurologic compromise

- No concurrent filgrastim (G-CSF) on day 1 of course 1

- No other concurrent anticancer therapy

- No other concurrent investigational therapy

Type of Study:


Study Design:

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Incidence of dose-limiting toxicity within first 3 courses of treatment

Safety Issue:


Principal Investigator

Darrell White, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Nova Scotia Cancer Centre


United States: Federal Government

Study ID:




Start Date:

December 2005

Completion Date:

June 2008

Related Keywords:

  • Multiple Myeloma and Plasma Cell Neoplasm
  • stage I multiple myeloma
  • stage II multiple myeloma
  • stage III multiple myeloma
  • Neoplasms
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma