Lenalidomide and Melphalan in Treating Patients With Previously Untreated Multiple Myeloma

This study has been completed.
Sponsor:
Information provided by:
NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00305812
First received: March 21, 2006
Last updated: November 7, 2010
Last verified: March 2010
  Purpose

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 Intervention Phase
Multiple Myeloma and Plasma Cell Neoplasm
Drug: dexamethasone
Drug: lenalidomide
Drug: melphalan
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: 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

Resource links provided by NLM:


Further study details as provided by NCIC Clinical Trials Group:

Primary Outcome Measures:
  • Incidence of dose-limiting toxicity within first 3 courses of treatment [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Toxicity [ Designated as safety issue: Yes ]
  • Disease response after 2 courses, 6 courses, 12 courses, and 6 months of maintenance therapy [ Designated as safety issue: No ]
  • Time to progression [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Duration of disease-free interval [ Designated as safety issue: No ]
  • Time to dose modification [ Designated as safety issue: No ]
  • Time to dose discontinuation [ Designated as safety issue: No ]

Estimated Enrollment: 92
Study Start Date: December 2005
Study Completion Date: June 2008
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00305812

Locations
Canada, Alberta
Tom Baker Cancer Centre - Calgary
Calgary, Alberta, Canada, T2N 4N2
Cross Cancer Institute at University of Alberta
Edmonton, Alberta, Canada, T6G 1Z2
Canada, British Columbia
British Columbia Cancer Agency - Centre for the Southern Interior
Kelowna, British Columbia, Canada, V1Y 5L3
Canada, New Brunswick
Moncton Hospital
Moncton, New Brunswick, Canada, E1C 6Z8
Canada, Nova Scotia
Nova Scotia Cancer Centre
Halifax, Nova Scotia, Canada, B3H 1V7
Canada, Ontario
Margaret and Charles Juravinski Cancer Centre
Hamilton, Ontario, Canada, L8V 5C2
London Regional Cancer Program at London Health Sciences Centre
London, Ontario, Canada, N6A 4L6
Algoma District Cancer Program at Sault Area Hospital
Sault Ste. Marie, Ontario, Canada, P6A 2C4
Humber River Regional Hospital - Weston
Toronto, Ontario, Canada, M9N 1N8
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Hopital Charles Lemoyne
Greenfield Park, Quebec, Canada, J4V 2H1
Hopital Notre-Dame du CHUM
Montreal, Quebec, Canada, H2L 4M1
McGill Cancer Centre at McGill University
Montreal, Quebec, Canada, H2W 1S6
Canada, Saskatchewan
Allan Blair Cancer Centre at Pasqua Hospital
Regina, Saskatchewan, Canada, S4T 7T1
Sponsors and Collaborators
NCIC Clinical Trials Group
Investigators
Study Chair: Darrell White, MD Nova Scotia Cancer Centre
  More Information

Additional Information:
Publications:
White DJ, Bahlis NJ, Marcellus DC, et al.: Phase II testing of lenalidomide plus melphalan for previously untreated older patients with multiple myeloma: the NCIC CTG MY.11 trial. [Abstract] Blood 112 (11): A-2767, 2008.
White DJ, Kovacs MJ, Belch A, et al.: Phase II testing of lenalidomide plus melphalan for previously untreated older patients with multiple myeloma: toxicity data from the NCIC CTG MY.11 trial. [Abstract] Blood 110 (11): A-189, 2007.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00305812     History of Changes
Other Study ID Numbers: MY11, CAN-NCIC-MY11, CELGENE-CAN-NCIC-MY11, CDR0000466184
Study First Received: March 21, 2006
Last Updated: November 7, 2010
Health Authority: United States: Federal Government

Keywords provided by NCIC Clinical Trials Group:
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma

Additional relevant MeSH terms:
Neoplasms
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Lenalidomide
Melphalan
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents

ClinicalTrials.gov processed this record on July 28, 2014