Combination Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Multiple Myeloma

NCT ID: NCT00005792

Last Updated: 2019-11-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 131 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1998-06-02
• Study Completion Date: 2018-11-01

Brief Summary

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.

PURPOSE: Phase I/II trial to study the effectiveness of combination chemotherapy plus peripheral stem cell transplantation in treating patients who have multiple myeloma.

Detailed Description

OBJECTIVES: I. Determine the toxicity and potential efficacy of intensive high dose chemotherapy consisting of melphalan, topotecan, and etoposide phosphate followed by autologous stem cell transplantation in patients with stage II or III multiple myeloma or stage I with evidence of progressive disease. II. Determine the maximum tolerated dose of topotecan in combination with melphalan and etoposide phosphate in this patient population. III. Determine response rates and time to treatment failure in these patients when treated with this regimen. IV. Determine the pharmacokinetic profiles of these drugs and investigate the pharmacodynamic relationships with respect to the efficacy and toxicity of this regimen in these patients. V. Determine whether the sequencing of this chemotherapy regimen is appropriate and optimal in these patients.

OUTLINE: This is a dose escalation study of topotecan. Patients are primed with cyclophosphamide IV over 2 hours for 2 days. Peripheral blood stem cells (PBSC) are collected. Approximately 4 weeks after PBSC collection, patients receive melphalan IV over 30 minutes and topotecan IV over 30 minutes on days -7 to -5. Etoposide phosphate IV is administered over 4 hours on days -4 and -3. PBSC are reinfused on day 0. Cohorts of 4-12 patients receive escalating doses of topotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 6 of 12 patients experience dose limiting toxicities. Patients are followed 2-3 times a week for approximately 1 month, then at 3, 6, and 12 months.

PROJECTED ACCRUAL: A total of 34-60 patients will be accrued for this study within 24-36 months.

Conditions

Multiple Myeloma; Plasma Cell Neoplasm

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MTV

Melphalan Topotecan Etoposide VP-16 Phosphate autologous stem cell transplant

Group Type: EXPERIMENTAL

etoposide phosphate

Intervention Type: DRUG

Etoposide phosphate 1363 mg/m\^2/day IV over 4 hours (total dose 2726 mg/m\^2, or 2400 mg/m\^2 etoposide equivalents), beginning 24 hours after the completion of the last infusion of topotecan Days -4, -3

melphalan

Intervention Type: DRUG

Melphalan 50 mg/m\^2/day IV over 30 minutes (total dose 150 mg/m\^2), followed immediately by topotecan. Days -7, -6, -5

topotecan

Intervention Type: DRUG

Topotecan 3.3 mg/m\^2/day (starting total dose = 10 mg/m\^2 for level 2) IV over 30 minutes. No topotecan will be administered on the first dose level Days -7, -6, -5

Autologous Stem Cell Rescue

Intervention Type: PROCEDURE

reinfusion of stem cells, Day 0

Interventions

etoposide phosphate

Etoposide phosphate 1363 mg/m\^2/day IV over 4 hours (total dose 2726 mg/m\^2, or 2400 mg/m\^2 etoposide equivalents), beginning 24 hours after the completion of the last infusion of topotecan Days -4, -3

Intervention Type: DRUG

melphalan

Melphalan 50 mg/m\^2/day IV over 30 minutes (total dose 150 mg/m\^2), followed immediately by topotecan. Days -7, -6, -5

Intervention Type: DRUG

topotecan

Topotecan 3.3 mg/m\^2/day (starting total dose = 10 mg/m\^2 for level 2) IV over 30 minutes. No topotecan will be administered on the first dose level Days -7, -6, -5

Intervention Type: DRUG

Autologous Stem Cell Rescue

reinfusion of stem cells, Day 0

Intervention Type: PROCEDURE

Other Intervention Names

Topotecan; Alkeran(R); Autologous stem cell transplant

Eligibility Criteria

Inclusion Criteria

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior total dose of doxorubicin or daunorubicin greater than 450 mg/m2 No prior topotecan or any other topoisomerase I inhibitor, etoposide, etoposide phosphate, or teniposide Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified Other: No concurrent nitroglycerin preparations for angina pectoris No concurrent antiarrhythmic drugs for major ventricular dysrhythmias

• Minimum Eligible Age: 15 Years
• Maximum Eligible Age: 69 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

SmithKline Beecham

INDUSTRY

Sponsor Role: collaborator

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

H. Lee Moffitt Cancer Center and Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Daniel M. Sullivan, M.D.

Role: STUDY_CHAIR

H. Lee Moffitt Cancer Center and Research Institute

Locations

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Countries

United States

Other Identifiers

MCC-11752

Identifier Type: OTHER

Identifier Source: secondary_id

IRB-4983

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-G00-1749

Identifier Type: OTHER

Identifier Source: secondary_id

MCC-11752

Identifier Type: -

Identifier Source: org_study_id