Clinical trial NCT00049673: Thalidomide and Prednisone After Autologous Stem Cell Transplantation Multiple Myeloma
Official title: A Randomized Phase III Study Of Thalidomide And Prednisone As Maintenance Therapy Following Autologous Stem Cell Transplant in Patients With Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Myeloma and Plasma Cell Neoplasm
Keywords: stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
Lead sponsor: Canadian Cancer Trials Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: Eastern Cooperative Oncology Group
First posted: 2003-01-27
Enrollment: 332
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall Survival
timeFrame: 9 years
Secondary outcomes:
measure: Disease Progression-free Survival
timeFrame: 9 years
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Vancouver
country: Canada
facility: BCCA - Vancouver Cancer Centre
state: British Columbia
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Moncton
country: Canada
facility: The Moncton Hospital
state: New Brunswick
city: Saint John
country: Canada
facility: Atlantic Health Sciences Corporation
state: New Brunswick
city: St. John's
country: Canada
facility: Dr. H. Bliss Murphy Cancer Centre
state: Newfoundland and Labrador
city: Halifax
country: Canada
facility: QEII Health Sciences Center
state: Nova Scotia
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre at Hamilton Health Sciences
state: Ontario
city: Kingston
country: Canada
facility: Cancer Centre of Southeastern Ontario at Kingston
state: Ontario
city: London
country: Canada
facility: London Regional Cancer Program
state: Ontario
city: Toronto
country: Canada
facility: Odette Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Univ. Health Network-Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: Hopital Maisonneuve-Rosemont
state: Quebec
city: Montreal
country: Canada
facility: McGill University - Dept. Oncology
state: Quebec
city: Quebec City
country: Canada
facility: CHA-Hopital Du St-Sacrement
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre hospitalier universitaire de Sherbrooke
state: Quebec
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre
state: Saskatchewan
Study officials:
affiliation: Mayo Clinic
name: A. Keith Stewart, MD
role: STUDY_CHAIR
affiliation: Mayo Clinic
name: Martha Q. Lacy, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.