Amifostine and Melphalan in Treating Patients With Primary Systemic Amyloidosis Who Are Undergoing Peripheral Stem Cell Transplantation

This study has been terminated.
(Slow accrual and changes in clinical practice)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier:
NCT00052884
First received: January 24, 2003
Last updated: November 30, 2012
Last verified: November 2012
  Purpose

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of plasma cells, either by killing the cells or by stopping them from dividing. Having a peripheral stem cell transplant to replace the blood-forming cells destroyed by chemotherapy, allows higher dose of chemotherapy to be given so that more plasma cells are killed. Giving a chemoprotective drug such as amifostine may protect kidney cells from the side effects of chemotherapy.

PURPOSE: This phase I trial is studying the side effects and best dose of melphalan given together with amifostine in treating patients who are undergoing peripheral stem cell transplant for primary systemic amyloidosis.


Condition Intervention Phase
Drug/Agent Toxicity by Tissue/Organ
Multiple Myeloma and Plasma Cell Neoplasm
Biological: filgrastim
Drug: amifostine trihydrate
Drug: melphalan
Procedure: bone marrow ablation with stem cell support
Procedure: peripheral blood stem cell transplantation
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Amifostine Followed by High-Dose Escalation of Melphalan With Stem Cell Reconstitution for Patients With Primary Systemic Amyloidosis

Resource links provided by NLM:


Further study details as provided by Eastern Cooperative Oncology Group:

Primary Outcome Measures:
  • Maximum Tolerated Dose [ Time Frame: Assessed over 30 days ] [ Designated as safety issue: Yes ]
    The maximum tolerated dose is the highest dose level at which fewer than 1 of 3 or 2 of 6 patients experience dose-limiting toxicity, defined as any grade 3 or higher toxicity of any of the following: renal failure, alkaline phosphatase elevation, GI bleeding, and cardiac rhythm disturbances, assessed using NCI Common Toxicity Criteria, version 2.0.


Enrollment: 8
Study Start Date: October 2003
Study Completion Date: March 2011
Primary Completion Date: September 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Amifostine, Melphalan, and Stem Cell Reconstitution
Amifostine, Melphalan, and Stem Cell Reconstitution. Doses of Melphalan tested included 100 mg/m2 and 120 mg/m2
Biological: filgrastim Drug: amifostine trihydrate Drug: melphalan Procedure: bone marrow ablation with stem cell support Procedure: peripheral blood stem cell transplantation

Detailed Description:

OBJECTIVES:

  • Determine the maximum tolerated dose (MTD) of high-dose melphalan administered with amifostine in patients with primary systemic amyloidosis undergoing autologous peripheral blood stem cell transplantation.
  • Determine the toxicity of high-dose melphalan when administered at the MTD in these patients.
  • Determine the response rate in patients treated with this regimen.

OUTLINE: This is a nonrandomized, multicenter, dose-escalation study of melphalan.

Patients receive filgrastim (G-CSF) subcutaneously once daily until peripheral blood stem cell (PBSC) collection is complete. Apheresis begins on day 5 of G-CSF administration and continues until the target number of PBSCs are collected.

Within 6 weeks of PBSC collection, patients receive amifostine IV over 5 minutes on days -2 and -1 and high-dose melphalan IV over 30-60 minutes on day -1. Patients undergo autologous PBSC infusion on day 0.

Cohorts of 3-6 patients receive escalating doses of melphalan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional 10 patients are treated at that dose.

Patients are followed approximately 3 months following transplantation, then every 6 months for 5 years.

PROJECTED ACCRUAL: A total of 3-46 patients will be accrued for this study within 2.3 years.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed amyloidosis

    • No secondary familial or localized amyloidosis
  • Presence of monoclonal protein by immunoelectrophoresis or immunofixation of serum or urine
  • No primary amyloidosis manifested only by carpal tunnel syndrome or purpura
  • Amyloid deposits in a plasmacytoma or in bone marrow vessels in an asymptomatic individual not considered an amyloid syndrome

    • Amyloid syndromes include any of the following:

      • Hepatomegaly
      • Cardiomyopathy
      • Nephrotic range proteinuria
      • Peripheral or autonomic neuropathy
  • No multiple myeloma defined by 1 of the following:

    • Presence of lytic bone disease
    • More than 30% bone marrow plasma cells

PATIENT CHARACTERISTICS:

Age

  • 18 to 70

Performance status

  • ECOG 0-1

Life expectancy

  • Not specified

Hematopoietic

  • Platelet count at least 100,000/mm^3

Hepatic

  • See Disease Characteristics
  • Total or direct bilirubin no greater than 2.0 mg/dL
  • Alkaline phosphatase no greater than 4 times upper limit of normal

Renal

  • See Disease Characteristics
  • Creatinine less than 3.0 mg/dL

Cardiovascular

  • See Disease Characteristics
  • Ejection fraction at least 45% by echocardiogram
  • No New York Heart Association class III or IV heart disease
  • Systolic blood pressure ≥ 90 mmHg

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No active infection
  • No other malignancy within the past 5 years except surgically treated carcinoma in situ of the cervix, nonmelanoma skin cancer, or indolent prostate cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • At least 4 weeks since prior interferon

Chemotherapy

  • At least 4 weeks since prior melphalan
  • Lifetime total melphalan dose less than 150 mg/m^2 (based on ideal body weight)

Endocrine therapy

  • At least 4 weeks since prior dexamethasone

Radiotherapy

  • No prior radiotherapy for amyloidosis

Surgery

  • Not specified

Other

  • No antihypertensive medications for at least 24 hours prior to, during, and for 1 hour after amifostine administration
  • No other prior treatment
  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: NCT00052884

Locations
United States, Arizona
Mayo Clinic Scottsdale
Scottsdale, Arizona, United States, 85259-5499
United States, Indiana
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202-5289
United States, Minnesota
Fairview Ridges Hospital
Burnsville, Minnesota, United States, 55337
Mercy and Unity Cancer Center at Mercy Hospital
Coon Rapids, Minnesota, United States, 55433
Fairview Southdale Hospital
Edina, Minnesota, United States, 55435
Mercy and Unity Cancer Center at Unity Hospital
Fridley, Minnesota, United States, 55432
Minnesota Oncology Hematology, PA - Maplewood
Maplewood, Minnesota, United States, 55109
Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
Minneapolis, Minnesota, United States, 55407
Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center
Robbinsdale, Minnesota, United States, 55422-2900
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
CCOP - Metro-Minnesota
Saint Louis Park, Minnesota, United States, 55416
Park Nicollet Cancer Center
St. Louis Park, Minnesota, United States, 55416
United Hospital
St. Paul, Minnesota, United States, 55102
Ridgeview Medical Center
Waconia, Minnesota, United States, 55387
Minnesota Oncology Hematology, PA - Woodbury
Woodbury, Minnesota, United States, 55125
United States, Ohio
Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106-5065
Sponsors and Collaborators
Eastern Cooperative Oncology Group
Investigators
Study Chair: Morie A. Gertz, MD Mayo Clinic
  More Information

No publications provided

Responsible Party: Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT00052884     History of Changes
Other Study ID Numbers: CDR0000258785, U10CA021115, ECOG-E2A01
Study First Received: January 24, 2003
Last Updated: November 30, 2012
Health Authority: United States: Federal Government

Keywords provided by Eastern Cooperative Oncology Group:
drug/agent toxicity by tissue/organ
primary systemic amyloidosis

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Amyloidosis
Plasmacytoma
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Proteostasis Deficiencies
Metabolic Diseases
Melphalan
Amifostine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 30, 2014