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

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Primary Purpose

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

etoposide phosphate

melphalan

topotecan

Autologous Stem Cell Rescue

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring refractory multiple myeloma, stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma

Eligibility Criteria

15 Years - 69 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

H. Lee Moffitt Cancer Center and Research Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

MTV

Arm Description

Melphalan Topotecan Etoposide VP-16 Phosphate autologous stem cell transplant

Outcomes

Primary Outcome Measures

Incidence of mucositis

To determine the incidence and duration of CTCAE v3, grade 3 or 4 mucositis for modified dose level four.

Secondary Outcome Measures

Full Information

NCT ID

NCT00005792

First Posted

June 2, 2000

Last Updated

November 6, 2019

Sponsor

H. Lee Moffitt Cancer Center and Research Institute

Collaborators

SmithKline Beecham, Bristol-Myers Squibb

1. Study Identification

Unique Protocol Identification Number

NCT00005792

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2019

Overall Recruitment Status

Completed

Study Start Date

June 2, 1998 (Actual)

Primary Completion Date

July 1, 2006 (Actual)

Study Completion Date

November 1, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

H. Lee Moffitt Cancer Center and Research Institute

Collaborators

SmithKline Beecham, Bristol-Myers Squibb

4. Oversight

Data Monitoring Committee

No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Myeloma, Plasma Cell Neoplasm

Keywords

refractory multiple myeloma, stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

131 (Actual)

8. Arms, Groups, and Interventions

Arm Title

MTV

Arm Type

Experimental

Arm Description

Melphalan Topotecan Etoposide VP-16 Phosphate autologous stem cell transplant

Intervention Type

Drug

Intervention Name(s)

etoposide phosphate

Other Intervention Name(s)

Topotecan

Intervention 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

Intervention Type

Drug

Intervention Name(s)

melphalan

Other Intervention Name(s)

Alkeran(R)

Intervention 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

Intervention Type

Drug

Intervention Name(s)

topotecan

Intervention 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

Intervention Type

Procedure

Intervention Name(s)

Autologous Stem Cell Rescue

Other Intervention Name(s)

Autologous stem cell transplant

Intervention Description

reinfusion of stem cells, Day 0

Primary Outcome Measure Information:

Title

Incidence of mucositis

Description

To determine the incidence and duration of CTCAE v3, grade 3 or 4 mucositis for modified dose level four.

Time Frame

5 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

15 Years

Maximum Age & Unit of Time

69 Years

Accepts Healthy Volunteers

No

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Daniel M. Sullivan, M.D.

Organizational Affiliation

H. Lee Moffitt Cancer Center and Research Institute

Official's Role

Study Chair

Facility Information:

Facility Name

H. Lee Moffitt Cancer Center and Research Institute

City

Tampa

State/Province

Florida

ZIP/Postal Code

33612-9497

Country

United States

12. IPD Sharing Statement

Links:

URL

https://moffitt.org/clinical-trials-research/

Description

Moffitt Cancer Center Clinical Trials website

Multiple Myeloma, Plasma Cell Neoplasm

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial