Combination Chemotherapy, Peripheral Stem Cell Transplantation, Biological Therapy, Pamidronate and Thalidomide in Treating Patients With Multiple Myeloma

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
City of Hope Medical Center Identifier:
First received: December 10, 1999
Last updated: December 16, 2013
Last verified: December 2013

RATIONALE: Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Peripheral stem cell transplantation may allow doctors to give higher doses of chemotherapy drugs and kill more cancer cells. Biological therapies, such as interferon alfa, use different ways to stimulate the immune system and stop cancer cells from growing. Thalidomide may stop the growth of cancer cells by stopping blood flow to the tumor. Pamidronate may help to reduce the side effects of treatment for multiple myeloma.

PURPOSE: This phase II trial is studying combination chemotherapy, peripheral stem cell transplantation, biological therapy, pamidronate, and thalidomide to see how well they work in treating patients with stage I, stage II, or stage III multiple myeloma.

Condition Intervention Phase
Multiple Myeloma and Plasma Cell Neoplasm
Biological: filgrastim
Biological: recombinant interferon alfa
Drug: busulfan
Drug: cyclophosphamide
Drug: melphalan
Drug: pamidronate disodium
Drug: thalidomide
Procedure: peripheral blood stem cell transplantation
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: Sequential High-Dose Melphalan and Busulfan/Cyclophosphamide Followed by Peripheral Blood Progenitor Cell Rescue, Interferon/Thalidomide and Pamidronate for Patients With Multiple Myeloma

Resource links provided by NLM:

Further study details as provided by City of Hope Medical Center:

Study Start Date: April 1999
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Detailed Description:


  • Determine the feasibility and toxic effects of high-dose melphalan, busulfan, and cyclophosphamide followed by autologous peripheral blood stem cell rescue, interferon alfa, and pamidronate in patients with responsive or stable, low-bulk multiple myeloma.
  • Determine the response rate and progression-free and overall survival of patients treated with this regimen.
  • Determine the feasibility of adding thalidomide to interferon alfa and pamidronate in patients who are not in complete remission (CR) 6 months after the second course of high-dose chemotherapy.
  • Determine whether administration of thalidomide can increase the CR rate in patients who are not in CR 6 months after the second course of high-dose chemotherapy and determine its effect on progression-free and overall survival of these patients.
  • Determine the pharmacokinetics of busulfan and cyclophosphamide and correlate the pharmacokinetics with the toxic effects of these drugs and outcome in these patients.
  • Determine the effect of thalidomide on microvascular density of bone marrow and correlate these possible effects with outcome in these patients.
  • Determine the cytogenetics, gene rearrangement, and fluorescence in situ hybridization in baseline and post treatment bone marrow and blood specimens and correlate the presence/persistence of these features with treatment outcome in these patients.

OUTLINE: Patients receive cyclophosphamide IV over 2 hours on day 1 and filgrastim (G-CSF) subcutaneously (SC) or IV twice a day beginning on day 2 and continuing until peripheral blood stem cells (PBSCs) are collected. PBSCs are collected beginning on day 10.

Patients receive high-dose melphalan IV on day -1. PBSCs are reinfused on day 0. G-CSF is administered IV or SC daily beginning on day 1 and continuing until blood counts recover. Between 8 and 14 weeks later, patients receive high-dose busulfan IV every 6 hours on days -7 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2. PBSCs are reinfused on day 0 and G-CSF is administered IV or SC daily until blood counts recover.

Patients with responding or stable disease after chemotherapy receive maintenance therapy with interferon alfa beginning 14-20 weeks after day 0 of the second course of chemotherapy. Interferon alfa is administered SC 3 times a week for 3 years. Patients also receive pamidronate IV every 4 weeks until disease progression. Patients who are not in complete remission (CR) 6 months after completing the second course of chemotherapy receive oral thalidomide daily for a maximum of 1 year or for 3 months after achieving CR.

Patients are followed monthly for 1 year, every 3 months for 1 year, and then periodically thereafter.

PROJECTED ACCRUAL: A total of 70 patients will be accrued for this study within approximately 2.5 years.


Ages Eligible for Study:   up to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No


  • Histologically proven stage I-III multiple myeloma

    • Less than 18 months since diagnosis
    • Smoldering myeloma allowed if there is evidence of progressive disease requiring therapy

      • At least 25% increase in M protein levels or Bence Jones excretion
      • Hemoglobin no greater than 10.5 g/dL
      • Hypercalcemia
      • Frequent infections
      • Rise in serum creatinine above normal on 2 separate occasions
    • Nonquantifiable monoclonal proteins allowed if other criteria for multiple myeloma or smoldering myeloma are met
  • Response/status after induction therapy:

    • Responding or stable disease AND no greater than 40% myelomatous involvement of bone marrow
  • No Waldenstrom's macroglobulinemia



  • 65 and under

Performance status:

  • Karnofsky 80-100%

Life expectancy:

  • Not specified


  • See Disease Characteristics
  • Absolute neutrophil count greater than 1,500/mm^3
  • Platelet count greater than 100,000/mm^3


  • Bilirubin no greater than 1.5 mg/dL
  • SGOT and SGPT less than 2.5 times upper limit of normal
  • Hepatitis B antigen or hepatitis C RNA negative


  • See Disease Characteristics
  • Creatinine no greater than 1.4 mg/dL
  • Creatinine clearance greater than 65 mL/min


  • Cardiac ejection fraction at least 50% by MUGA or echocardiogram


  • FEV_1 greater than 60%
  • DLCO greater than 50% of predicted lower limit


  • Not pregnant
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • HIV negative
  • No other medical or psychosocial problems that would increase patient risk
  • No other malignancy within past 5 years except nonmelanomatous skin cancer or carcinoma in situ of the cervix
  • No known hypersensitivity to filgrastim (G-CSF) or E. coli-derived proteins


Biologic therapy:

  • Not specified


  • See Disease Characteristics
  • No more than 3 prior chemotherapy regimens
  • At least 4 weeks since prior chemotherapy

Endocrine therapy:

  • Not specified


  • At least 4 weeks since prior radiotherapy


  • Not specified
  Contacts and Locations
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Please refer to this study by its identifier: NCT00004088

United States, Arizona
Banner Good Samaritan Medical Center
Phoenix, Arizona, United States, 85006
United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
Sponsors and Collaborators
City of Hope Medical Center
Principal Investigator: George Somlo, MD City of Hope Medical Center
  More Information

Additional Information:
No publications provided

Responsible Party: City of Hope Medical Center Identifier: NCT00004088     History of Changes
Other Study ID Numbers: 99021, P30CA033572, CHNMC-IRB-99021, NCI-G99-1583, CDR0000067301
Study First Received: December 10, 1999
Last Updated: December 16, 2013
Health Authority: United States: Federal Government

Keywords provided by City of Hope Medical Center:
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Interferon Alfa-2a
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors processed this record on July 20, 2014