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

June 14, 2023 updated by: Eastern Cooperative Oncology Group

A Phase I Study of Amifostine Followed by High-Dose Escalation of Melphalan With Stem Cell Reconstitution for Patients With Primary Systemic Amyloidosis

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

8

Phase

  • Phase 1

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

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

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 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

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: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
Drug: amifostine trihydrate
Procedure: peripheral blood stem cell transplantation
Biological: filgrastim
Drug: melphalan
Procedure: bone marrow ablation with stem cell support

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Tolerated Dose
Time Frame: Assessed over 30 days
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.
Assessed over 30 days

Collaborators and Investigators

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

Sponsor

Eastern Cooperative Oncology Group

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Morie A. Gertz, MD, Mayo Clinic

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 (Actual)

January 22, 2004

Primary Completion (Actual)

September 1, 2007

Study Completion (Actual)

March 1, 2011

Study Registration Dates

First Submitted

January 24, 2003

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimated)

January 27, 2003

Study Record Updates

Last Update Posted (Estimated)

June 16, 2023

Last Update Submitted That Met QC Criteria

June 14, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000258785
  • U10CA021115 (U.S. NIH Grant/Contract)
  • ECOG-E2A01

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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