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Phase III Randomized Study of Doxorubicin, Dexamethasone, and High-Dose Melphalan With or Without Thalidomide in Patients With Multiple Myeloma
Alternate Title Basic Trial Information Objectives Entry Criteria Expected Enrollment Outcomes Outline Published Results Related Publications Trial Contact Information Registry Information
Alternate Title
Combination Chemotherapy With or Without Thalidomide in Treating Patients With Multiple Myeloma
Basic Trial Information
Phase | Type | Status | Age | Protocol IDs |
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Phase III | Treatment | Closed | 18 to 65 | CKTO-2001-02 HOVON-50MM, EU-20133, HOVON-CKVO-2001-02, NCT00028886 |
Objectives - Compare the efficacy of doxorubicin, dexamethasone, and high-dose melphalan with versus without thalidomide, in terms of event-free survival, of patients with multiple myeloma.
- Determine the response rate, complete response rate, overall survival, and progression-free survival of patients treated with these regimens.
- Determine the safety and toxicity of thalidomide in combination with intensive chemotherapy in these patients.
- Assess the value of prognostic factors at diagnosis in individual patients treated with these regimens.
Entry Criteria Disease Characteristics:
- Histologically confirmed multiple myeloma
- No systemic amyloid light-chain amyloidosis
Prior/Concurrent Therapy:
Biologic therapy: - Patients 18 to 55 years of age must not have been allocated
before study randomization to allogeneic stem cell transplantation with an
HLA-identical sibling donor
Chemotherapy: - No more than 2 prior courses of melphalan and prednisone
therapy for local myeloma progression
- No other prior chemotherapy
Endocrine therapy: Radiotherapy: - Prior local radiotherapy for local myeloma progression
allowed
- No other prior radiotherapy
Surgery: Patient Characteristics:
Age: Performance status: Life expectancy: Hematopoietic: Hepatic: - No significant hepatic dysfunction*
- Bilirubin less than 1.75 mg/dL*
- AST/ALT less than 2.5 times normal*
[Note: *Unless related to myeloma] Renal: Cardiovascular: - No severe cardiac dysfunction
- No New York Heart Association class II, III, or IV heart
disease
Other: - HIV negative
- No active uncontrolled infection
- No other malignancy within the past 5 years except basal cell
skin cancer or carcinoma in situ of the cervix
- No known intolerance to thalidomide
- Not pregnant
- Negative pregnancy test
- Fertile patients must use effective contraception
Expected Enrollment 450A total of 450 patients (225 per treatment arm) will be accrued for this study
within 4 years. Outcomes Primary Outcome(s)Event-free survival
Secondary Outcome(s)Partial response and complete response Overall survival Progression-free survival Toxicity
Outline This is a randomized, multicenter study. Patients are stratified
according to participating center and treatment policy (1 course vs 2 courses
of high-dose melphalan). Patients are randomized to 1 of 2 treatment
arms. Arm I: - Patients receive induction chemotherapy (AD) comprising
doxorubicin IV on days 1-4 and oral dexamethasone on days 1-4, 9-12, and
17-20. Patients receive oral thalidomide daily beginning on day 1 and
continuing until 2 weeks before start of stem cell mobilization. Treatment
repeats every 28 days for 3 courses in the absence of disease progression or
unacceptable toxicity.
- Patients receive stem cell mobilization with chemotherapy comprising
cyclophosphamide IV on day 1 and doxorubicin IV and oral dexamethasone on days
1-4 (CAD). Patients also receive filgrastim (G-CSF) subcutaneously (SC)
beginning on day 5 and continuing until last apheresis.
- Beginning 8-10 weeks after stem cell collection, patients receive
low-dose oral thalidomide daily and high-dose melphalan IV on days -3 and -2
as intensification. Patients undergo stem cell infusion on day 0. Patients
may receive a second course of high-dose melphalan 2-3 months after the first
course, in which case, stem cell infusion follows the second course of
melphalan.
- Patients receive maintenance therapy with oral thalidomide daily until
disease progression or after 3 months if no response.
- Beginning 2 months after the last course, patients with an
HLA-identical sibling donor undergo nonmyeloablative stem cell transplantation
after radiotherapy.
Arm II: - Patients receive induction chemotherapy (VAD) comprising
vincristine IV and doxorubicin IV on days 1-4 and dexamethasone on days 1-4,
9-12, and 17-20. Treatment repeats every 28 days for 3 courses in the absence
of disease progression or unacceptable toxicity.
- Patients receive stem cell mobilization with CAD chemotherapy as in
arm I. G-CSF is given as in arm I.
- Patients receive high-dose melphalan and undergo stem cell infusion as
in arm I.
- Patients receive maintenance therapy with interferon alfa SC 3 times
weekly until progression or after 3 months if no partial response.
- Beginning 2 months after the last course, patients with an
HLA-identical sibling donor undergo nonmyeloablative stem cell transplantation
after radiotherapy.
All patients are followed every 6 months for 3 years and then annually
thereafter. Published ResultsLokhorst HM, Schmidt-Wolf I, Sonneveld P, et al.: Thalidomide in induction treatment increases the very good partial response rate before and after high-dose therapy in previously untreated multiple myeloma. Haematologica 93 (1): 124-7, 2008.[PUBMED Abstract] Lokhorst H, van der Holt B, Zweegman S, et al.: Final analysis of HOVON-50 randomized phase III study on the effect of thalidomide combined with adriamycine,dexamethasone (AD) and high dose melphalan (HDM) in patients with multiple myeloma (MM). [Abstract] Blood 112 (11): A-157, 2008. Related PublicationsJohnson DC, Corthals S, Ramos C, et al.: Genetic associations with thalidomide mediated venous thrombotic events in myeloma identified using targeted genotyping. Blood 112 (13): 4924-34, 2008.[PUBMED Abstract]
Trial Contact Information
Trial Lead Organizations Commissie Voor Klinisch Toegepast Onderzoek | | | H. Lokhorst, MD, PhD, Protocol chair | | | |
Registry Information | | Official Title | | A Randomized Phase III Study On The Effect Of Thalidomide Combined With Adriamycin, Dexamethasone (AD) And High Dose Melphalan In Patients With Multiple Myeloma | | Trial Start Date | | 2001-03-01 | | Registered in ClinicalTrials.gov | | NCT00028886 | | Date Submitted to PDQ | | 2001-10-30 | | Information Last Verified | | 2009-01-06 |
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol. Back to Top |
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