Combination Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Sarcoma

Phase 2

Completed

• Conditions: Sarcoma
• Interventions: Biological: filgrastim; Drug: cisplatin; Drug: doxorubicin hydrochloride; Drug: ifosfamide; Drug: melphalan; Procedure: peripheral blood stem cell transplantation

• Registration Number: NCT00002601
• Lead Sponsor: City of Hope Medical Center

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of high-dose combination chemotherapy and peripheral stem cell transplantation in treating patients who have advanced or recurrent sarcoma.

Detailed Description

OBJECTIVES: I. Determine the feasibility of sequential high-dose chemotherapy with ifosfamide and doxorubicin followed by melphalan and cisplatin, each followed by autologous peripheral blood stem cell support, in patients with high-risk or advanced sarcomas. II. Determine the toxic effects of this regimen in these patients. III. Determine response rate and disease-free and overall survival in these patients treated with this regimen.

OUTLINE: Beginning at least 4 weeks prior to the start of chemotherapy, patients receive filgrastim (G-CSF) subcutaneously daily until the completion of peripheral blood stem cell (PBSC) harvesting. Beginning 5 days after the start of G-CSF, PBSCs are collected over several days. Patients who do not mobilize sufficient cells undergo bone marrow harvest. Regimen A: Patients receive high-dose ifosfamide IV and doxorubicin IV continuously over 96 hours on days -8 to -4. 12.5% of PBSCs or bone marrow are reinfused on day -2 and 37.5% are reinfused on day 0. Patients receive G-CSF IV beginning on day 0 and continuing until blood counts recover. Regimen B: Beginning at least 4 weeks after day 1 of Regimen A, patients receive high-dose melphalan IV followed immediately by cisplatin IV on days -11 and -4. Patients receive G-CSF IV on days -10 to -6. 12.5% of PBSCs or bone marrow are reinfused on day -3 and the remaining 37.5% are reinfused on day 0. Patients receive G-CSF IV beginning on day 0 and continuing until blood counts recover. Patients are followed monthly for 1 year, every 3 months for 1 year, and then as needed for 3 years.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study within 3 years.

Study Timeline

• Study Start: 1994-09
• Study First Submitted: 1999-11-01
• Study First Submitted QC: 2004-03-10
• Study First Posted: 2004-03-11
• Primary Completion: 2014-09
• Study Completion: 2014-09
• Results First Submitted: 2016-11-21
• Results First Submitted QC: 2016-11-21
• Status Verified: 2017-01
• Last Update Submitted: 2017-01-18
• Results First Posted: 2017-01-19
• Last Update Posted: 2017-03-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 13

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Doxorubicin/Ifosfamide + Melphalan/CDDP + PSCT	filgrastim	Cycle 1 Day -8 through Day -4 (96h) Doxorubicin 150 mg/m2 (CI) + Ifosfamide 14 g/m2 mixed with mesna (CI) Day -3 Mesna 3.5 g/m2 over 24 h Day -2 12.5% of stem cell reinfused. Cycle2 Day -11 Melphalan 75 mg/m2 + Cisplatin 100 mg/m2 Day -10 thru Day -6 G-CSF 5ug/kg Day -4 Melphalan 75 mg/m2 + Cisplatin 100 mg/m2 Day -3 12.5% if stem cell reinfused Day 0 37.5% of stem cell reinfused
Doxorubicin/Ifosfamide + Melphalan/CDDP + PSCT	peripheral blood stem cell transplantation	Cycle 1 Day -8 through Day -4 (96h) Doxorubicin 150 mg/m2 (CI) + Ifosfamide 14 g/m2 mixed with mesna (CI) Day -3 Mesna 3.5 g/m2 over 24 h Day -2 12.5% of stem cell reinfused. Cycle2 Day -11 Melphalan 75 mg/m2 + Cisplatin 100 mg/m2 Day -10 thru Day -6 G-CSF 5ug/kg Day -4 Melphalan 75 mg/m2 + Cisplatin 100 mg/m2 Day -3 12.5% if stem cell reinfused Day 0 37.5% of stem cell reinfused
Doxorubicin/Ifosfamide + Melphalan/CDDP + PSCT	cisplatin	Cycle 1 Day -8 through Day -4 (96h) Doxorubicin 150 mg/m2 (CI) + Ifosfamide 14 g/m2 mixed with mesna (CI) Day -3 Mesna 3.5 g/m2 over 24 h Day -2 12.5% of stem cell reinfused. Cycle2 Day -11 Melphalan 75 mg/m2 + Cisplatin 100 mg/m2 Day -10 thru Day -6 G-CSF 5ug/kg Day -4 Melphalan 75 mg/m2 + Cisplatin 100 mg/m2 Day -3 12.5% if stem cell reinfused Day 0 37.5% of stem cell reinfused
Doxorubicin/Ifosfamide + Melphalan/CDDP + PSCT	doxorubicin hydrochloride	Cycle 1 Day -8 through Day -4 (96h) Doxorubicin 150 mg/m2 (CI) + Ifosfamide 14 g/m2 mixed with mesna (CI) Day -3 Mesna 3.5 g/m2 over 24 h Day -2 12.5% of stem cell reinfused. Cycle2 Day -11 Melphalan 75 mg/m2 + Cisplatin 100 mg/m2 Day -10 thru Day -6 G-CSF 5ug/kg Day -4 Melphalan 75 mg/m2 + Cisplatin 100 mg/m2 Day -3 12.5% if stem cell reinfused Day 0 37.5% of stem cell reinfused
Doxorubicin/Ifosfamide + Melphalan/CDDP + PSCT	ifosfamide	Cycle 1 Day -8 through Day -4 (96h) Doxorubicin 150 mg/m2 (CI) + Ifosfamide 14 g/m2 mixed with mesna (CI) Day -3 Mesna 3.5 g/m2 over 24 h Day -2 12.5% of stem cell reinfused. Cycle2 Day -11 Melphalan 75 mg/m2 + Cisplatin 100 mg/m2 Day -10 thru Day -6 G-CSF 5ug/kg Day -4 Melphalan 75 mg/m2 + Cisplatin 100 mg/m2 Day -3 12.5% if stem cell reinfused Day 0 37.5% of stem cell reinfused
Doxorubicin/Ifosfamide + Melphalan/CDDP + PSCT	melphalan	Cycle 1 Day -8 through Day -4 (96h) Doxorubicin 150 mg/m2 (CI) + Ifosfamide 14 g/m2 mixed with mesna (CI) Day -3 Mesna 3.5 g/m2 over 24 h Day -2 12.5% of stem cell reinfused. Cycle2 Day -11 Melphalan 75 mg/m2 + Cisplatin 100 mg/m2 Day -10 thru Day -6 G-CSF 5ug/kg Day -4 Melphalan 75 mg/m2 + Cisplatin 100 mg/m2 Day -3 12.5% if stem cell reinfused Day 0 37.5% of stem cell reinfused

Primary Outcome Measures

Name	Time	Method
Toxicities Counts	2 months after completion of second cycle of treatment.	Number of patients with grade 3 and 4 toxicities observed during cycles 1 \& 2 using the Common Toxicity Criteria Version for Chemotherapy.
Number of Participants With Grade 3 Bilirubin	2 years after completion of treatment	Criteria for early termination of this feasibility study: \> 2 patients experience grade 4 or 5 hematologic toxicity or more that 3 patients experience grade 3 hematologic toxicity; \> 2 patients experience grade 3 hepatic or gastrointestinal toxicity or \> 3 patients are unable to receive the second cycle of treatment; \> 2 patients experience grade 5 toxicity related to treatment regimen.

Secondary Outcome Measures

Name	Time	Method
5-year Progression-free Survival	Until disease progression, up to 5 Years	Estimated using the product-limit method of Kaplan and Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 25% increase in the sum of the longest diameter of target lesions, or the appearance of new lesions.
5-year Overall Survival	Until death from any cause, up to 5 years	Estimated using the product-limit method of Kaplan and Meier.

Trial Locations

Locations (1)

Cancer Center and Beckman Research Institute, City of Hope; 🇺🇸 Duarte, California, United States