Lenalidomide and Melphalan in Treating Patients With Previously Untreated Multiple Myeloma

Sponsor

NCIC Clinical Trials Group (Other)

Overall Status

Completed

CT.gov ID

NCT00305812

Collaborator

(none)

Enrollment

Locations

30.6

Actual Duration (Months)

3.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Lenalidomide may stop the growth of multiple myeloma by blocking blood flow to the cancer. It may also stimulate the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving lenalidomide together with melphalan may kill more cancer cells.

PURPOSE: This randomized phase II trial is studying the side effects and best dose of lenalidomide when given together with melphalan and to see how well they work in treating patients with multiple myeloma.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma and Plasma Cell Neoplasm	Drug: dexamethasone Drug: lenalidomide Drug: melphalan	Phase 2

Detailed Description

OBJECTIVES:

Primary

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.

Secondary

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 dexamethasone.
Determine progression-free and overall survival of these patients.
Determine time to dose modification and time to dose discontinuation in these patients.

Tertiary

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 toxicity.

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

51 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Dec 13, 2005

Actual Primary Completion Date :

Jun 30, 2008

Actual Study Completion Date :

Jun 30, 2008

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Toxicity []
Disease response after 2 courses, 6 courses, 12 courses, and 6 months of maintenance therapy []
Time to progression []
Overall survival []
Duration of disease-free interval []
Time to dose modification []
Time to dose discontinuation []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

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 criteria
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

PATIENT CHARACTERISTICS:

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

PRIOR CONCURRENT THERAPY:

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 allowed
No concurrent filgrastim (G-CSF) on day 1 of course 1
No other concurrent anticancer therapy
No other concurrent investigational therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tom Baker Cancer Centre - Calgary	Calgary	Alberta	Canada	T2N 4N2
2	Cross Cancer Institute at University of Alberta	Edmonton	Alberta	Canada	T6G 1Z2
3	British Columbia Cancer Agency - Centre for the Southern Interior	Kelowna	British Columbia	Canada	V1Y 5L3
4	Moncton Hospital	Moncton	New Brunswick	Canada	E1C 6Z8
5	Nova Scotia Cancer Centre	Halifax	Nova Scotia	Canada	B3H 1V7
6	Margaret and Charles Juravinski Cancer Centre	Hamilton	Ontario	Canada	L8V 5C2
7	London Regional Cancer Program at London Health Sciences Centre	London	Ontario	Canada	N6A 4L6
8	Algoma District Cancer Program at Sault Area Hospital	Sault Ste. Marie	Ontario	Canada	P6A 2C4
9	Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
10	Humber River Regional Hospital - Weston	Toronto	Ontario	Canada	M9N 1N8
11	Hopital Charles Lemoyne	Greenfield Park	Quebec	Canada	J4V 2H1
12	Hopital Notre-Dame du CHUM	Montreal	Quebec	Canada	H2L 4M1
13	McGill Cancer Centre at McGill University	Montreal	Quebec	Canada	H2W 1S6
14	Allan Blair Cancer Centre at Pasqua Hospital	Regina	Saskatchewan	Canada	S4T 7T1