Thalidomide and Prednisone After Autologous Stem Cell Transplantation Multiple Myeloma

A Randomized Phase III Study Of Thalidomide And Prednisone As Maintenance Therapy Following Autologous Stem Cell Transplant in Patients With Multiple Myeloma

RATIONALE: Thalidomide may stop the growth of multiple myeloma by stopping blood flow to the tumor. It is not yet known whether combining thalidomide with prednisone and giving them after autologous stem cell transplantation may be effective in treating multiple myeloma.

PURPOSE: This randomized phase III trial is studying thalidomide and prednisone to see how well they work compared to observation in treating patients who have undergone stem cell transplantation for multiple myeloma.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma and Plasma Cell Neoplasm
• Intervention / Treatment: Drug: prednisone; Drug: thalidomide

Detailed Description

OBJECTIVES:

• Compare overall survival of patients with multiple myeloma treated with thalidomide and prednisone as maintenance therapy vs observation alone after autologous stem cell transplantation.
• Compare progression-free survival of patients treated with these regimens.
• Compare quality of life of patients treated with these regimens.
• Compare toxic effects of these regimens in these patients.
• Compare the objective venous thromboembolism rate in symptomatic patients treated with these regimens.

OUTLINE: This is a randomized, non-blinded, multicenter study. Patients are stratified according to treatment center, age (under 60 vs 60 and over), and response to prior transplantation (complete vs incomplete). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral thalidomide daily and oral prednisone every other day for 4 years in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients undergo observation.

For both arms, patients are assessed (including for quality of life) regularly throughout the treatment/observation period: at baseline, every 2 months for 6 months, every 3 months for up to 4 years, and then annually thereafter.

After the treatment/observation period, patients are followed annually..

PROJECTED ACCRUAL: A total of 324 patients will be accrued for this study within 3.5 years.

• Study Type: Interventional
• Enrollment (Actual): 332
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BCCA - Vancouver Cancer Centre
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • CancerCare Manitoba
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 6Z8
      • The Moncton Hospital
    • Saint John, New Brunswick, Canada, E2L 4L2
      • Atlantic Health Sciences Corporation
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, AIB 3V6
      • Dr. H. Bliss Murphy Cancer Centre
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • QEII Health Sciences Center
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Juravinski Cancer Centre at Hamilton Health Sciences
    • Kingston, Ontario, Canada, K7L 5P9
      • Cancer Centre of Southeastern Ontario at Kingston
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Program
    • Toronto, Ontario, Canada, M4N 3M5
      • Odette Cancer Centre
    • Toronto, Ontario, Canada, M5G 2M9
      • Univ. Health Network-Princess Margaret Hospital
  • Quebec
    • Montreal, Quebec, Canada, H2W 1S6
      • McGill University - Dept. Oncology
    • Montreal, Quebec, Canada, H1T 2M4
      • Hôpital Maisonneuve-Rosemont
    • Quebec City, Quebec, Canada, G1S 4L8
      • CHA-Hopital Du St-Sacrement
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Centre Hospitalier Universitaire de Sherbrooke
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Saskatoon Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed multiple myeloma as evidenced 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 at least 10% plasmacytosis
  • Bone marrow less than 10% plasma cells with at least 1 bony lesion and meets the M-protein criteria as below
• Detectable serum M-component of IgG, IgA, IgD, or IgE at initial diagnosis OR
• Urinary excretion of light chain (Bence Jones) protein at least 1.0 gm/24 hrs if only light chain disease (urine M-protein) was present at initial diagnosis

• Previously treated with autologous stem cell transplantation after high-dose melphalan (200 mg/m^2) within the past 60-100 days

  • Received transplantation within 1 year of the beginning of initial chemotherapy for multiple myeloma
  • No evidence of disease progression

PATIENT CHARACTERISTICS:

Age

• 16 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 6 months

Hematopoietic

• No prior hereditary hypercoaguable disorder
• Granulocyte count at least 1,000/mm^3
• Platelet count at least 75,000/mm^3

Hepatic

• Bilirubin no greater than 2 times upper limit of normal (ULN)
• AST and/or ALT no greater than 2 times ULN
• Alkaline phosphatase no greater than 2 times ULN

Renal

• Creatinine no greater than 3 times ULN

Cardiovascular

• No prior spontaneous deep vein thrombosis within the past 5 years

  • Catheter-associated thrombus allowed
• No uncontrolled hypertension

Pulmonary

• No prior pulmonary embolism within the past 5 years

Other

• No other prior or concurrent malignancy except adequately treated squamous cell or basal cell skin cancer or carcinoma in situ of the cervix or any cancer treated more than 5 years prior to study entry and presumed cured
• No prior gastric ulceration or bleeding within the past 5 years
• No prior documented lupus anti-coagulant or anti-phospholipid antibody
• Not pregnant or nursing
• Negative pregnancy test
• Fertile female patients must use 2 effective methods of contraception for 1 month prior, during, and 1 month after study participation
• Male patients must use effective barrier contraception during and for 1 month after study participation
• No avascular necrosis of the hips or shoulders
• No grade 2 or greater peripheral neuropathy causing symptomatic dysfunction (vincristine-induced sensory symptoms allowed)

• No diabetes with end-organ damage defined as:

  • Documented diabetic neuropathy
  • Retinal vascular proliferation requiring treatment
  • Cardiovascular disease requiring active therapy
• Willing to complete quality of life questionnaires
• Employment does not prohibit the use of sedatives
• No other major medical illness or condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics
• No prior double autologous or allogeneic hematopoietic stem cell transplantation
• No prior thalidomide

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• No other concurrent anti-cancer therapy
• No other concurrent investigational therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I; Patients receive oral thalidomide daily and oral prednisone every other day for 4 years in the absence of disease progression or unacceptable toxicity.	Drug: prednisone; Given orally; Drug: thalidomide; Given orally
No Intervention: Arm II; Patients undergo observation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Number of patients died from any cause during the study.	9 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Progression-free Survival	Number of patients with disease progression or death	9 years

Collaborators and Investigators

• Sponsor: NCIC Clinical Trials Group
• Collaborators: National Cancer Institute (NCI); Eastern Cooperative Oncology Group
• Investigators: Study Chair: Martha Q. Lacy, MD, Mayo Clinic; Study Chair: A. Keith Stewart, MD, Mayo Clinic

Publications and helpful links

General Publications

• Stewart AK, Trudel S, Bahlis NJ, White D, Sabry W, Belch A, Reiman T, Roy J, Shustik C, Kovacs MJ, Rubinger M, Cantin G, Song K, Tompkins KA, Marcellus DC, Lacy MQ, Sussman J, Reece D, Brundage M, Harnett EL, Shepherd L, Chapman JA, Meyer RM. A randomized phase 3 trial of thalidomide and prednisone as maintenance therapy after ASCT in patients with MM with a quality-of-life assessment: the National Cancer Institute of Canada Clinicals Trials Group Myeloma 10 Trial. Blood. 2013 Feb 28;121(9):1517-23. doi: 10.1182/blood-2012-09-451872. Epub 2013 Jan 7.
• Kovacs MJ, Davies GA, Chapman JA, Bahlis N, Voralia M, Roy J, Kouroukis CT, Chen C, Belch A, Reece D, Zhu L, Meyer RM, Shepherd L, Stewart KA. Thalidomide-prednisone maintenance following autologous stem cell transplant for multiple myeloma: effect on thrombin generation and procoagulant markers in NCIC CTG MY.10. Br J Haematol. 2015 Feb;168(4):511-7. doi: 10.1111/bjh.13176. Epub 2014 Oct 10.

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2002
• Primary Completion (Actual): October 19, 2011
• Study Completion (Actual): September 19, 2013

Study Registration Dates

• First Submitted: November 12, 2002
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimated): January 27, 2003

Study Record Updates

• Last Update Posted (Actual): September 13, 2023
• Last Update Submitted That Met QC Criteria: September 7, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: stage II multiple myeloma; stage III multiple myeloma; stage I multiple myeloma
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Plasmacytoma; Physiological Effects of Drugs; Anti-Infective Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Thalidomide; Prednisone
• Other Study ID Numbers: MY10; CAN-NCIC-JMY10 (Other Identifier: PDQ); ECOG-NCIC-JMY10 (Other Identifier: ECOG); CELGENE-CAN-NCIC-MY10 (Other Identifier: Celgene); CDR0000258158 (Other Identifier: PDQ)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No