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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
SmithKline Beecham
Bristol-Myers Squibb
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:
NCT00005792
First received: June 2, 2000
Last updated: June 11, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma
Plasma Cell Neoplasm
Drug: etoposide phosphate
Drug: melphalan
Drug: topotecan
Procedure: Autologous Stem Cell Rescue
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Study of Intensive-Dose Melphalan, Topotecan, and VP-16 Phosphate (MTV) Followed by Autologous Stem Cell Rescue in Patients With Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:
  • Incidence of mucositis [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
    To determine the incidence and duration of CTCAE v3, grade 3 or 4 mucositis for modified dose level four.


Enrollment: 131
Study Start Date: June 1998
Estimated Study Completion Date: December 2014
Primary Completion Date: September 2001 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MTV
Melphalan Topotecan Etoposide VP-16 Phosphate autologous stem cell transplant
Drug: etoposide phosphate
Etoposide phosphate 1363 mg/m2/day IV over 4 hours (total dose 2726 mg/m2, or 2400 mg/m2 etoposide equivalents), beginning 24 hours after the completion of the last infusion of topotecan Days -4, -3
Other Name: Topotecan
Drug: melphalan
Melphalan 50 mg/m2/day IV over 30 minutes (total dose 150 mg/m2), followed immediately by topotecan. Days -7, -6, -5
Other Name: Alkeran(R)
Drug: topotecan
Topotecan 3.3 mg/m2/day (starting total dose = 10 mg/m2 for level 2) IV over 30 minutes. No topotecan will be administered on the first dose level Days -7, -6, -5
Other Name: topotecan
Procedure: Autologous Stem Cell Rescue
reinfusion of stem cells, Day 0
Other Name: Autologous stem cell transplant

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.

  Eligibility

Ages Eligible for Study:   15 Years to 69 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS: Histologically confirmed multiple myeloma Newly diagnosed, drug sensitive (i.e., greater than 50% response to standard chemotherapy), and poor prognostic indicators (e.g., Salmon-Durie stage III, serum beta-2-microglobulin greater than 3.0 ug/L, high proliferative fraction, or hypodiploidy) OR Relapsed after a response to standard chemotherapy OR Primary refractory disease No active leptomeningeal involvement History of prior CSF tumor involvement without symptoms or signs allowed provided CSF is now free of disease on lumbar puncture and MRI of brain shows no tumor involvement No severe symptomatic CNS disease of any etiology

PATIENT CHARACTERISTICS: Age: 15 to 69 Performance status: ECOG 0-1 ECOG 3-4 secondary to bone pain or a potentially reversible disease related problem eligible at investigator's discretion Life expectancy: At least 12 weeks Hematopoietic: Not specified Hepatic: Bilirubin no greater than 2.0 mg/dL SGOT/SGPT no greater than 2.5 times upper limit of normal No history of severe hepatic dysfunction Renal: Creatinine no greater than 2.0 mg/dL OR Creatinine at least 40 mL/min No hemodialysis or peritoneal dialysis Cardiovascular: No evidence of severe cardiac dysfunction Ejection fraction at least 50% by MUGA scan No major heart disease Essential hypertension controlled with medications allowed Pulmonary: DLCO at least 50% of normal No symptomatic obstructive or restrictive pulmonary disease Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No psychosocial disorder that would preclude study compliance No active infections No uncontrolled insulin dependent diabetes mellitus No uncompensated major thyroid or adrenal dysfunction No other prior malignancy except for nonmelanoma skin cancer HIV negative

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

  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: NCT00005792

Locations
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612-9497
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
SmithKline Beecham
Bristol-Myers Squibb
Investigators
Study Chair: Daniel M. Sullivan, M.D. H. Lee Moffitt Cancer Center and Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT00005792     History of Changes
Other Study ID Numbers: MCC-11752, MCC-11752, IRB-4983, NCI-G00-1749
Study First Received: June 2, 2000
Last Updated: June 11, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
refractory multiple myeloma
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma

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

ClinicalTrials.gov processed this record on July 24, 2014