A Study of Intensive-Dose Melphalan, Topotecan, and VP-16 Phosphate (MTV) Followed by Autologous Stem Cell Rescue in Patients With Multiple Myeloma
15 Years
69 Years
Both
Multiple Myeloma, Plasma Cell Neoplasm
Trial Information
A Study of Intensive-Dose Melphalan, Topotecan, and VP-16 Phosphate (MTV) Followed by Autologous Stem Cell Rescue in Patients With Multiple Myeloma
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Incidence of mucositis
Outcome Description:
to determine the incidence and duration of CTCAE v3, grade 3 or 4 mucositis for modified dose level four.
Outcome Time Frame:
5 years
Safety Issue:
Yes
Principal Investigator
Daniel M. Sullivan, MD
Investigator Role:
Study Chair
Investigator Affiliation:
H. Lee Moffitt Cancer Center and Research Institute
Authority:
United States: Food and Drug Administration
Study ID:
11752
NCT ID:
NCT00005792
Start Date:
June 1998
Completion Date:
June 2013
Related Keywords:
- Multiple Myeloma
- Plasma Cell Neoplasm
- refractory multiple myeloma
- stage I multiple myeloma
- stage II multiple myeloma
- stage III multiple myeloma
- Neoplasms
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Plasmacytoma
Name | Location |
|---|---|
| H. Lee Moffitt Cancer Center and Research Institute | Tampa, Florida 33612 |
