Combination Chemotherapy With or Without Thalidomide in Treating Patients With Multiple Myeloma

September 16, 2013 updated by: Commissie Voor Klinisch Toegepast Onderzoek

A Randomized Phase III Study On The Effect Of Thalidomide Combined With Adriamycin, Dexamethasone (AD) And High Dose Melphalan In Patients With Multiple Myeloma

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Thalidomide may stop the growth of cancer cells by stopping blood flow to the cancer. Peripheral blood stem cell transplant using stem cells from the patient or a donor may be able to replace immune cells that were destroyed by chemotherapy used to kill cancer cells. The donated stem cells may also help destroy any remaining cancer cells (graft-versus-tumor effect). It is not yet known whether chemotherapy followed by peripheral blood stem cell transplant is more effective with or without thalidomide in treating multiple myeloma.

PURPOSE: This randomized phase III trial is studying giving combination chemotherapy with thalidomide to see how well it works compared with giving combination chemotherapy without thalidomide in treating patients with multiple myeloma.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

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.

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.

PROJECTED ACCRUAL: A total of 450 patients (225 per treatment arm) will be accrued for this study within 4 years.

Study Type

Interventional

Enrollment (Anticipated)

450

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Leuven, Belgium, B-3000
        • U.Z. Gasthuisberg
  • Netherlands
      • 's-Gravenhage, Netherlands, 2545 CH
        • HagaZiekenhuis - Locatie Leyenburg
      • 's-Hertogenbosch, Netherlands, 5211 NL
        • Jeroen Bosch Ziekenhuis
      • Amersfoort, Netherlands, 3816 CP
        • Meander Medisch Centrum
      • Amsterdam, Netherlands, 1066 CX
        • Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
      • Amsterdam, Netherlands, 1105 AZ
        • Academisch Medisch Centrum at University of Amsterdam
      • Amsterdam, Netherlands, 1081HV
        • Vrije Universiteit Medisch Centrum
      • Enschede, Netherlands, 7500 KA
        • Medisch Spectrum Twente
      • Groningen, Netherlands, 9713 EZ
        • University Medical Center Groningen
      • Leeuwarden, Netherlands, 8934 AD
        • Medisch Centrum Leeuwarden - Zuid
      • Leiden, Netherlands, 2300 RC
        • Leiden University Medical Center
      • Maastricht, Netherlands, 6202 AZ
        • Academisch Ziekenhuis Maastricht
      • Nieuwegein, Netherlands, 3435 CM
        • Sint Antonius Ziekenhuis
      • Nijmegen, Netherlands, NL-6500 HB
        • Universitair Medisch Centrum St. Radboud - Nijmegen
      • Rotterdam, Netherlands, 3008 AE
        • Daniel Den Hoed Cancer Center at Erasmus Medical Center
      • Utrecht, Netherlands, 3584 CX
        • University Medical Center Utrecht
      • Zwolle, Netherlands, 8000 GK
        • Isala Klinieken - locatie Sophia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed multiple myeloma

    • Stage II or III
  • No systemic amyloid light-chain amyloidosis

PATIENT CHARACTERISTICS:

Age:

  • 18 to 65

Performance status:

  • WHO 0-3

Life expectancy:

  • Not specified

Hematopoietic:

  • Not specified

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:

  • Not specified

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

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:

  • Not specified

Radiotherapy:

  • Prior local radiotherapy for local myeloma progression allowed
  • No other prior radiotherapy

Surgery:

  • Not specified

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Event-free survival

Secondary Outcome Measures

Outcome Measure
Toxicity
Progression-free survival
Overall survival
Partial response and complete response

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Commissie Voor Klinisch Toegepast Onderzoek

Investigators

  • Study Chair: H. Lokhorst, MD, PhD, UMC Utrecht

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2001

Study Registration Dates

First Submitted

January 4, 2002

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

September 17, 2013

Last Update Submitted That Met QC Criteria

September 16, 2013

Last Verified

October 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000069144
  • CKTO-2001-02
  • HOVON-50MM
  • EU-20133
  • HOVON-CKVO-2001-02

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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