Filgrastim Compared With Sargramostim Plus Chemotherapy, Peripheral Stem Cell Transplantation, and Interferon Alfa in Treating Patients With Multiple Myeloma

This study has been terminated.
(Withdrawn because treatment guidelines changed)
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT00005987
First received: July 5, 2000
Last updated: October 9, 2012
Last verified: October 2012
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. Colony-stimulating factors such as filgrastim and sargramostim may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy. Interferon alfa may interfere with the growth of cancer cells. It is not yet known which treatment regimen is more effective for multiple myeloma.

PURPOSE: Randomized phase II trial to compare the effectiveness of filgrastim with that of sargramostim plus chemotherapy, peripheral stem cell transplantation, and interferon alfa in treating patients who have multiple myeloma.


Condition Intervention Phase
Multiple Myeloma and Plasma Cell Neoplasm
Drug: carmustine
Drug: cyclophosphamide
Drug: dexamethasone
Drug: etoposide
Drug: filgrastim
Drug: mitoxantrone hydrochloride
Drug: recombinant interferon alfa
Drug: sargramostim
Procedure: bone marrow ablation with stem cell support
Procedure: peripheral blood stem cell transplantation
Procedure: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Treatment
Official Title: Autologous Transplantation for Multiple Myeloma: A Research Study of Multiple Myeloma Using Chemotherapy Plus Growth Factor Primed Peripheral Blood Stem Cells Followed by Autologous Transplantation and Post-Transplant Immunotherapy

Resource links provided by NLM:


Further study details as provided by Masonic Cancer Center, University of Minnesota:

Enrollment: 87
Study Start Date: August 2000
Study Completion Date: July 2003
Primary Completion Date: July 2003 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • Compare disease control and extended survival in patients with multiple myeloma when treated with either filgrastim (G-CSF) or sargramostim (GM-CSF) plus high-dose chemotherapy followed by autologous peripheral blood stem cell (PBSC) transplantation followed by interferon alfa.
  • Determine whether these priming treatments induce sufficient mobilization of circulating PBSC to allow their collection by leukapheresis for subsequent use in autologous transplantation in these patients.
  • Determine whether these treatments induce complete response in conjunction with rapid hematopoietic recovery and modest transplant-associated morbidity and mortality in this patient population.
  • Determine whether interferon alfa, given as maintenance immunostimulatory therapy for patients achieving significant cytoreduction post transplantation, can prevent or delay malignant relapse in these patients.

OUTLINE: This is a randomized study. Patients are randomized to one of two treatment arms.

  • Arm I: In the priming phase, patients receive cyclophosphamide IV over 2 hours on day 1, mitoxantrone IV over 1 hour daily on days 1-2, and dexamethasone IV every 12 hours beginning on day 1 for a total of 4 doses. Patients also receive sargramostim (GM-CSF) IV over 2 hours or subcutaneously (SC) daily beginning 48 hours after the last dose of mitoxantrone and continuing until completion of leukapheresis. Peripheral blood stem cells (PBSC) are collected daily on days 11-13 after neutrophil recovery.
  • Arm II: In the priming phase, patients receive the same treatment as in arm I except these patients receive filgrastim (G-CSF) IV over 15 minutes or SC in place of GM-CSF.

In the transplant phase, patients who have not received prior radiotherapy receive cyclophosphamide IV over 2 hours daily on days -6 and -5 and total body irradiation twice daily on days -3 through -1. Autologous PBSC are reinfused on day 0. Patients also receive GM-CSF IV over 2 hours daily and G-CSF IV over 15 minutes daily beginning on day 0 and continuing until day 28 or until blood counts recover.

Patients who have received prior radiotherapy receive cyclophosphamide IV over 2 hours daily on days -6 through -3, carmustine IV over 1 hour on day -6, and etoposide IV over 4 hours every 12 hours for a total of 6 doses on days -6 through -4. Autologous PBSC are reinfused on day 0. Patients also receive GM-CSF IV over 2 hours daily and G-CSF IV over 15 minutes daily beginning on day 0 and continuing until day 28 or until blood counts recover.

All patients then receive interferon alfa SC 3 times weekly starting on day 28 and continuing until relapse or disease progression.

Patients may also undergo radiotherapy 5 days a week for 2 weeks for residual bony lesions measuring greater than 2 cm.

Patients are followed at days 28 and 100, and at 6, 9, 12, 18, 24, 30, and 36 months.

PROJECTED ACCRUAL: A total of 25-35 patients will be accrued for this study within 2-3 years.

  Eligibility

Ages Eligible for Study:   up to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed multiple myeloma

    • Complete or partial remission after initial therapy OR
    • Complete or partial response to therapy after disease progression following initial therapy
    • No plasma cell leukemia (greater than 10% circulating plasma cells)
    • No advanced myeloma refractory and unresponsive to at least 2 salvage chemotherapy regimens

PATIENT CHARACTERISTICS:

Age:

  • 70 and under

Performance status:

  • Age 65-70 years:

    • Karnofsky 80-100%
  • Under 65 years:

    • Not specified

Life expectancy:

  • Not specified

Hematopoietic:

  • Hemoglobin at least 8 g/dL (untransfused)
  • WBC at least 3,000/mm^3
  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3 (untransfused)

Hepatic:

  • Bilirubin less than 2.0 mg/dL
  • ALT less than 3 times upper limit of normal

Renal:

  • Age 65-70 years:

    • Creatinine clearance greater than 60 mL/min (if creatinine at least 1.5 mg/dL)
  • Under 65 years:

    • Creatinine less than 2 mg/dL

Cardiovascular:

  • Age 65-70 years:

    • LVEF at least 45%
  • Under 65 years:

    • No active ischemia
    • LVEF greater than 45% by MUGA

Pulmonary:

  • Age 65-70 years:

    • If history of smoking or respiratory symptoms, spirometry and DLCO must be greater than 50% of predicted
  • Under 65 years:

    • FEV_1 and FVC greater than 60% predicted
    • DLCO greater than 50% of predicted

Other:

  • No active or uncontrolled infection

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Not specified

Chemotherapy:

  • See Disease Characteristics

Endocrine therapy:

  • Not specified

Radiotherapy:

  • See Disease Characteristics

Surgery:

  • Not specified
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00005987

Locations
United States, Minnesota
University of Minnesota Cancer Center
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Study Chair: Daniel J. Weisdorf, MD Masonic Cancer Center, University of Minnesota
  More Information

No publications provided

Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT00005987     History of Changes
Other Study ID Numbers: 1996LS137, UMN-MT-9216, UMN-MT-1992-16
Study First Received: July 5, 2000
Last Updated: October 9, 2012
Health Authority: United States: Federal Government

Keywords provided by Masonic Cancer Center, University of Minnesota:
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
Cyclophosphamide
Dexamethasone
Interferon-alpha
Interferons
Lenograstim
Mitoxantrone
Adjuvants, Immunologic
Alkylating Agents
Analgesics
Anti-Infective Agents
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal

ClinicalTrials.gov processed this record on October 22, 2014