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Combination Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Multiple Myeloma
This study is ongoing, but not recruiting participants.
First Received: June 2, 2000   Last Updated: February 6, 2009   History of Changes
Sponsors and Collaborators: H. Lee Moffitt Cancer Center and Research Institute
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00005792
  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 and Plasma Cell Neoplasm
Drug: cyclophosphamide
Drug: etoposide phosphate
Drug: melphalan
Drug: topotecan hydrochloride
Procedure: peripheral blood stem cell transplantation
Phase I
Phase II

Genetics Home Reference related topics: aceruloplasminemia hemophilia
MedlinePlus related topics: Cancer Multiple Myeloma
Drug Information available for: Cyclophosphamide Etoposide Etoposide phosphate Topotecan hydrochloride Topotecan Melphalan Sarcolysin Melphalan hydrochloride
U.S. FDA Resources
Study Type: Interventional
Study Design: 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

Further study details as provided by National Cancer Institute (NCI):

Study Start Date: July 2000
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
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
Investigators
Study Chair: Daniel M. Sullivan, MD H. Lee Moffitt Cancer Center and Research Institute
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000067746, MCC-11752, MCC-IRB-4983, NCI-G00-1749
Study First Received: June 2, 2000
Last Updated: February 6, 2009
ClinicalTrials.gov Identifier: NCT00005792     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
refractory multiple myeloma
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma

Study placed in the following topic categories:
Melphalan
Immunoproliferative Disorders
Immunologic Factors
Blood Protein Disorders
Hematologic Diseases
Blood Coagulation Disorders
Vascular Diseases
Paraproteinemias
Cyclophosphamide
Hemostatic Disorders
Immunosuppressive Agents
Etoposide phosphate
Multiple Myeloma
Hemorrhagic Disorders
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Topotecan
Lymphoproliferative Disorders
Antineoplastic Agents, Phytogenic
Alkylating Agents
Etoposide
Neoplasms, Plasma Cell

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

ClinicalTrials.gov processed this record on May 07, 2009