Amifostine to Protect From Side Effects of PSCT in Treating Patients With Solid Tumors

November 27, 2017 updated by: Masonic Cancer Center, University of Minnesota

A Phase I Study of the Chemoprotectant Amifostine With Autologous Stem Cell Transplantation for High Risk or Relapsed Pediatric Solid Tumors and Brain Tumors

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Chemoprotective drugs such as amifostine may protect normal cells from the side effects of high-dose chemotherapy.

PURPOSE: Phase I trial to study the effectiveness of amifostine in protecting from the side effects of peripheral stem cell transplantation in treating patients who have high-risk or relapsed solid tumors.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Determine the dose-limiting toxicity of amifostine chemoprotection with peripheral blood stem cell transplantation plus chemotherapy in patients with high-risk or relapsed solid tumors or brain tumors.
  • Determine response or time to disease progression in patients treated with this regimen.

OUTLINE: This is a dose-escalation study of amifostine. Patients are stratified according to age (1 to 18 vs 19 to 45 years).

All patients receive filgrastim (G-CSF) IV for 1 week. On day 6 of G-CSF administration, patients undergo peripheral blood stem cell (PBSC) harvest followed by chemotherapy.

Patients receive oral busulfan every 6 hours on days -8 to -6 followed by melphalan IV over 30 minutes on days -5 and -4 and thiotepa IV over 2 hours on days -3 and -2. Patients receive amifostine IV over 5 minutes beginning 30 minutes prior to melphalan and thiotepa administration on days -5 to -1. PBSC are reinfused on day 0.

Cohorts of 3-6 patients receive escalating doses of amifostine until the maximum tolerated dose is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed on day 50; at 3, 6, and 9 months; and at 1, 2, and 3 years post PBSC transplantation.

PROJECTED ACCRUAL: A maximum of 60 patients (30 per stratum) will be accrued for this study within 3 years.

Study Type

Interventional

Enrollment (Actual)

13

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
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota 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

1 year to 45 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically confirmed high-risk or relapsed solid tumors or brain tumors, including:

    • Metastatic or relapsed Ewing's sarcoma
    • Metastatic or relapsed rhabdomyosarcoma
    • Refractory Wilms' tumor
    • Diffuse anaplastic Wilms' tumor
    • Stage III or IV neuroblastoma
    • Recurrent retinoblastoma
    • Metastatic or relapsed germ cell tumors
    • Metastatic or relapsed other soft tissue sarcomas
    • Small cell ovarian sarcoma
    • Metastatic or relapsed primitive neuroectodermal tumors of the bone
    • Recurrent brain tumors
    • Desmoplastic small round cell tumors
    • Recurrent or metastatic chordomas
    • Metastatic or relapsed hepatoblastoma
  • Patients receive peripheral blood stem cell transplantation only if in complete remission or in very good partial remission with no disease progression
  • Must have radiologic, nuclear image, or histologic verification of relapse
  • Age 1 to 45
  • Performance status:Karnofsky 70-100%
  • Absolute neutrophil count greater than 1,000/mm^3
  • Platelet count greater than 100,000/mm^3
  • Hemoglobin count at least 10 g/dL
  • Bilirubin less than 2 times upper limit of normal (ULN)
  • SGOT or SGPT less than 2.5 times ULN
  • Creatinine less than 2 times ULN
  • Creatinine clearance greater than 70 mL/min
  • Cardiac shortening fraction greater than 30%
  • Cardiac ejection fraction greater than 45%
  • At least 1 week since prior hematopoietic growth factor and recovered
  • At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered
  • Recovered from any prior therapy

Exclusion Criteria:

  • Osteogenic sarcoma
  • Less than 4 months
  • Uncontrolled bleeding
  • Congestive heart failure
  • Uncontrolled hypertension
  • Asthma
  • Pregnant or nursing
  • Uncontrolled metabolic disease
  • Active severe infection
  • Allergy to aminothiol compounds
  • Prior bone marrow transplantation
  • Other concurrent investigational agents

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: Supportive Care
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Solid/brain tumor patients (1-18 years)
Patients with solid tumor or brain tumor in the 1-18 years old stratum.
Drug: amifostine trihydrate

Patients receive amifostine intravenous (IV) over 5 minutes beginning 30 minutes prior to melphalan and thiotepa administration on days -5 to -1.

Cohorts of 3-6 patients receive escalating doses of amifostine until the maximum tolerated dose is determined.

Other Names:
  • Ethyol
Drug: busulfan
Patients receive oral busulfan every 6 hours on days -8 to -6.
Other Names:
  • Busulfex
Drug: filgrastim
All patients receive filgrastim (G-CSF) IV for 1 week.
Other Names:
  • G-CSF
  • granulocyte colony-stimulating factor
Drug: melphalan
melphalan intravenous (IV) over 30 minutes on days -5 and -4
Other Names:
  • Alkeran
Drug: thiotepa
thiotepa intravenous (IV) over 2 hours on days -3 and -2.
Other Names:
  • Thioplex
Procedure: peripheral blood stem cell transplantation (PBSC)
PBSC are reinfused on day 0
Other Names:
  • bone marrow transplant
Experimental: Solid/brain tumor patients (19-45 years)
Patients with solid tumor or brain tumor in the 19-45 years old stratum.
Drug: amifostine trihydrate

Patients receive amifostine intravenous (IV) over 5 minutes beginning 30 minutes prior to melphalan and thiotepa administration on days -5 to -1.

Cohorts of 3-6 patients receive escalating doses of amifostine until the maximum tolerated dose is determined.

Other Names:
  • Ethyol
Drug: busulfan
Patients receive oral busulfan every 6 hours on days -8 to -6.
Other Names:
  • Busulfex
Drug: filgrastim
All patients receive filgrastim (G-CSF) IV for 1 week.
Other Names:
  • G-CSF
  • granulocyte colony-stimulating factor
Drug: melphalan
melphalan intravenous (IV) over 30 minutes on days -5 and -4
Other Names:
  • Alkeran
Drug: thiotepa
thiotepa intravenous (IV) over 2 hours on days -3 and -2.
Other Names:
  • Thioplex
Procedure: peripheral blood stem cell transplantation (PBSC)
PBSC are reinfused on day 0
Other Names:
  • bone marrow transplant

Collaborators and Investigators

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

Sponsor

Masonic Cancer Center, University of Minnesota

Investigators

  • Study Chair: John P. Perentesis, MD, Masonic Cancer Center, University of Minnesota

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

November 1, 1998

Primary Completion (Actual)

August 1, 2002

Study Completion (Actual)

August 1, 2003

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

May 1, 2003

First Posted (Estimate)

May 2, 2003

Study Record Updates

Last Update Posted (Actual)

November 29, 2017

Last Update Submitted That Met QC Criteria

November 27, 2017

Last Verified

November 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1997LS053
  • UMN-MT-9713 (Other Identifier: Blood and Marrow Transplantation Program)
  • UMN-9712M00074 (Other Identifier: IRB, University of Minnesota)

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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