Expired Study
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Tampa, Florida 33612


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.


Study summary:

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.


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


Study is Available At:


Original ID:

MCC-11752


NCT ID:

NCT00005792


Secondary ID:

MCC-11752


Study Acronym:


Brief Title:

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


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


Overall Status:

Completed


Study Phase:

Phase 1


Genders:

N/A


Minimum Age:

15 Years


Maximum Age:

69 Years


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

H. Lee Moffitt Cancer Center and Research Institute


Oversight Authority:

United States: Food and Drug Administration


Reasons Why Stopped:


Study Type:

Interventional


Study Design:


Number of Arms:

1


Number of Groups:

0


Total Enrollment:

131


Enrollment Type:

Actual


Overall Contact Information

Official Name:Daniel M. Sullivan, M.D.
Study Chair
H. Lee Moffitt Cancer Center and Research Institute

Study Dates

Start Date:June 2, 1998
Completion Date:November 1, 2018
Completion Type:Actual
Primary Completion Date:July 1, 2006
Primary Completion Type:Actual
Verification Date:November 2019
Last Changed Date:November 6, 2019
First Received Date:June 2, 2000

Study Outcomes

Outcome Type:Primary Outcome
Measure:Incidence of mucositis
Time Frame:5 years
Safety Issues:False
Description:To determine the incidence and duration of CTCAE v3, grade 3 or 4 mucositis for modified dose level four.

Study Interventions

Intervention Type:Drug
Name:etoposide phosphate
Description: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
Arm Name:MTV
Other Name:Topotecan
Intervention Type:Drug
Name:melphalan
Description:Melphalan 50 mg/m^2/day IV over 30 minutes (total dose 150 mg/m^2), followed immediately by topotecan. Days -7, -6, -5
Arm Name:MTV
Other Name:Alkeran(R)
Intervention Type:Drug
Name:topotecan
Description: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
Arm Name:MTV
Intervention Type:Procedure
Name:Autologous Stem Cell Rescue
Description:reinfusion of stem cells, Day 0
Arm Name:MTV
Other Name:Autologous stem cell transplant

Study Arms

Study Arm Type:Experimental
Arm Name:MTV
Description:Melphalan Topotecan Etoposide VP-16 Phosphate autologous stem cell transplant

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:H. Lee Moffitt Cancer Center and Research Institute
Agency Class:Industry
Agency Type:Collaborator
Agency Name:SmithKline Beecham

Sample and Retention Information

There are no available Sample and Retention Information

Study References

There are no available Study References

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

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