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DTPACE Followed by Tandem Transplant With Melphalan (MEL) 200 Versus MEL/Dexamethasone/Thalidomide (DT) Platinol/Adriamycin/Etoposide (PACE) Hybrid and DTPACE Consolidation

Primary Purpose

Multiple Myeloma

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Cisplatin
Cyclophosphamide
Adriamycin
Etoposide
Melphalan
Thalidomide
Dexamethasone
Sponsored by
University of Arkansas
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring Multiple Myeloma, DTPACE, Tandem Transplant, Cisplatin, Cyclophosphamide, Dexamethasone, Doxorubicin, Etoposide, Sargramostim, Thalidomide, Melphalan

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients must have active multiple myeloma requiring treatment. Patients that have received >450 mg/m2 of prior Adriamycin therapy are eligible, however, Adriamycin will be deleted from the DT PACE regimen in these patients, unless the left ventricular ejection fraction is > 55% on Multi-gated Acquisition Scan (MUGA) or Echocardiogram (ECHO). If the patient has had > 450 mg/m2 of prior adriamycin, the LVEF must be evaluated prior to every cycle of DT PACE and it must be > 55% for patient to continue to receive adriamycin. All necessary baseline studies for determining eligibility must be obtained within 35 days prior to registration. Patients must have a performance status of 0-2 based on Southwest Oncology Group (SWOG) criteria. Patients with a poor performance status (3-4), based solely on bone pain, will be eligible. Patients must have a platelet count greater than or equal to 100,000/microliters. Patients with platelet count <100,000/microliters may be enrolled if it is felt to be due to extensive marrow plasmacytosis. Patients must have a creatinine <3 mg/dl and a creatinine clearance greater than or equal to 30 ml/minute. Patients with a creatinine clearance of 30-50 ml will only receive a 50% cisplatin dose. Patients must have adequate hepatic function defined as serum transaminases < 2 x Upper limit of normal (ULN) and direct bilirubin < 2.0 mg/dl. Patients must be able to receive full doses of DT PACE, in the opinion of the treating investigator, with some exception of: Patients that have received prior adriamycin > 450 mg/m2 and left ventricular ejection fraction (LVEF) < 55% or patients with a creatinine clearance 30 - 50 ml/minute, who will receive 50% of the cisplatin dose. All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines. Exclusion Criteria: Patients must not have significant co-morbid medical conditions or uncontrolled life threatening infection. Patients must not have received a prior autotransplant or allograft. Patients with recent (less than or equal to 6 months) myocardial infarction, unstable angina, difficult to control congestive heart failure, uncontrolled hypertension, or difficult to control cardiac arrythmias are ineligible. Ejection fraction by ECHO or must be greater than or equal to 50% and must be performed within 60 days prior to registration, unless the patient has received chemotherapy within that period of time (dexamethasone and thalidomide excluded), in which case the LVEF must be repeated. Patients must not have a history of chronic obstructive or chronic restrictive pulmonary disease. No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease free for at least three years.Prior malignancy is acceptable provided there has been no evidence of disease within the three-year interval. Pregnant or nursing women may not participate. Patients must not have significant co-morbid medical conditions or uncontrolled life threatening infection. Patients must not have a history of chronic obstructive or chronic restrictive pulmonary disease. Patients must have adequate pulmonary function studies greater than or equal to 50% of predicted on mechanical aspects (FEV1, forced vital capacity (FVC) and diffusion capacity (DLCO) greater than or equal to 50% of predicted. Patients unable to complete pulmonary function tests due to myeloma related pain or fracture must have a high resolution CT scan of the chest and must also have acceptable arterial blood gases defined as P02 greater than 70.

Sites / Locations

  • University of Arkansas for Medical Sciences/MIRT

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Auto Transplant w/ High Dose Melphalan

Auto Transplant w/ Melphalan + DT Pace

Arm Description

Autologous transplant with High Dose Melphalan alone

Melphalan plus Dexamethasone, Thalidomide, CisPlatinum, Adriamycin, Cyclophosphamide, and Etoposide

Outcomes

Primary Outcome Measures

Transplant With DT PACE-Melphalan Regimen of Chemotherapy vs. Transplant With Melphalan Alone.
Compare a new regimen of chemotherapy called DT PACE-Melphalan (new experimental therapy) is better than transplant with Melphalan alone (standard therapy)

Secondary Outcome Measures

Full Information

First Posted
June 3, 2004
Last Updated
October 17, 2017
Sponsor
University of Arkansas
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1. Study Identification

Unique Protocol Identification Number
NCT00083915
Brief Title
DTPACE Followed by Tandem Transplant With Melphalan (MEL) 200 Versus MEL/Dexamethasone/Thalidomide (DT) Platinol/Adriamycin/Etoposide (PACE) Hybrid and DTPACE Consolidation
Official Title
University of Arkansas (UARK 2001-12), A Phase III Study of DTPACE Followed by Tandem Transplant With MEL 200 Versus MEL/DTPACE Hybrid and DTPACE Consolidation in Patients With Active Multiple Myeloma
Study Type
Interventional

2. Study Status

Record Verification Date
October 2017
Overall Recruitment Status
Completed
Study Start Date
June 2001 (undefined)
Primary Completion Date
June 2010 (Actual)
Study Completion Date
June 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Arkansas

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to find out if transplant with a new regimen of chemotherapy called DT PACE-Melphalan is better than transplant with Melphalan alone. DT-PACE refers to a chemotherapy regimen for multiple myeloma consisting of Dexamethasone, Thalidomide, Cisplatin or Platinol, Adriamycin or doxorubicin, Cyclophosphamide, and Etoposide. Another purpose of this study is to find out if there will be fewer side effects with the new regimen of DT PACE-Melphalan, compared to melphalan alone.
Detailed Description
To evaluate, in a randomized phase III clinical trial in previously treated multiple myeloma patients, whether angio-chemotherapy with D.T. PACE followed by tandem transplant with MEL-DTPACE Hybrid may be equivalent or superior to tandem transplant with high dose melphalan in terms of complete remission (CR)/near CR/very good partial remission (VGPR) rate and event-free and overall survival.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Multiple Myeloma, DTPACE, Tandem Transplant, Cisplatin, Cyclophosphamide, Dexamethasone, Doxorubicin, Etoposide, Sargramostim, Thalidomide, Melphalan

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
97 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Auto Transplant w/ High Dose Melphalan
Arm Type
Active Comparator
Arm Description
Autologous transplant with High Dose Melphalan alone
Arm Title
Auto Transplant w/ Melphalan + DT Pace
Arm Type
Active Comparator
Arm Description
Melphalan plus Dexamethasone, Thalidomide, CisPlatinum, Adriamycin, Cyclophosphamide, and Etoposide
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Other Intervention Name(s)
Cisplatinum, cis-diamminedichloroplatinum, Platinol, Platinol-injectable (AQ)
Intervention Description
20mg/m2 continuous infusion days -3 and -2.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Endoxan, Cytoxan, Neosar, Procytox, Revimmune
Intervention Description
800 mg/m2 continuous infusion days -3 and -2.
Intervention Type
Drug
Intervention Name(s)
Adriamycin
Other Intervention Name(s)
hydroxydaunorubicin, Doxorubicin
Intervention Description
20mg/m2 continuous infusion -3 and -2.
Intervention Type
Drug
Intervention Name(s)
Etoposide
Other Intervention Name(s)
Eposin, Etopophos, Vepesid
Intervention Description
80mg/m2 continuous infusion -3 and -2.
Intervention Type
Drug
Intervention Name(s)
Melphalan
Other Intervention Name(s)
alkeran
Intervention Description
200 mg/m2 IV over <20 minutes on -1 on Arm 1. 50mg/m2 IV over 20 minutes days -3 and -2 on Arm 2.
Intervention Type
Drug
Intervention Name(s)
Thalidomide
Other Intervention Name(s)
Thalomid
Intervention Description
200mg PO Continuing to Day +5, then hold until platelets >50 thousand (K).
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Other Intervention Name(s)
Decadron
Intervention Description
40 mg po days 1 - 4 (4 days)
Primary Outcome Measure Information:
Title
Transplant With DT PACE-Melphalan Regimen of Chemotherapy vs. Transplant With Melphalan Alone.
Description
Compare a new regimen of chemotherapy called DT PACE-Melphalan (new experimental therapy) is better than transplant with Melphalan alone (standard therapy)
Time Frame
3 years depending on start date

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have active multiple myeloma requiring treatment. Patients that have received >450 mg/m2 of prior Adriamycin therapy are eligible, however, Adriamycin will be deleted from the DT PACE regimen in these patients, unless the left ventricular ejection fraction is > 55% on Multi-gated Acquisition Scan (MUGA) or Echocardiogram (ECHO). If the patient has had > 450 mg/m2 of prior adriamycin, the LVEF must be evaluated prior to every cycle of DT PACE and it must be > 55% for patient to continue to receive adriamycin. All necessary baseline studies for determining eligibility must be obtained within 35 days prior to registration. Patients must have a performance status of 0-2 based on Southwest Oncology Group (SWOG) criteria. Patients with a poor performance status (3-4), based solely on bone pain, will be eligible. Patients must have a platelet count greater than or equal to 100,000/microliters. Patients with platelet count <100,000/microliters may be enrolled if it is felt to be due to extensive marrow plasmacytosis. Patients must have a creatinine <3 mg/dl and a creatinine clearance greater than or equal to 30 ml/minute. Patients with a creatinine clearance of 30-50 ml will only receive a 50% cisplatin dose. Patients must have adequate hepatic function defined as serum transaminases < 2 x Upper limit of normal (ULN) and direct bilirubin < 2.0 mg/dl. Patients must be able to receive full doses of DT PACE, in the opinion of the treating investigator, with some exception of: Patients that have received prior adriamycin > 450 mg/m2 and left ventricular ejection fraction (LVEF) < 55% or patients with a creatinine clearance 30 - 50 ml/minute, who will receive 50% of the cisplatin dose. All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines. Exclusion Criteria: Patients must not have significant co-morbid medical conditions or uncontrolled life threatening infection. Patients must not have received a prior autotransplant or allograft. Patients with recent (less than or equal to 6 months) myocardial infarction, unstable angina, difficult to control congestive heart failure, uncontrolled hypertension, or difficult to control cardiac arrythmias are ineligible. Ejection fraction by ECHO or must be greater than or equal to 50% and must be performed within 60 days prior to registration, unless the patient has received chemotherapy within that period of time (dexamethasone and thalidomide excluded), in which case the LVEF must be repeated. Patients must not have a history of chronic obstructive or chronic restrictive pulmonary disease. No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease free for at least three years.Prior malignancy is acceptable provided there has been no evidence of disease within the three-year interval. Pregnant or nursing women may not participate. Patients must not have significant co-morbid medical conditions or uncontrolled life threatening infection. Patients must not have a history of chronic obstructive or chronic restrictive pulmonary disease. Patients must have adequate pulmonary function studies greater than or equal to 50% of predicted on mechanical aspects (FEV1, forced vital capacity (FVC) and diffusion capacity (DLCO) greater than or equal to 50% of predicted. Patients unable to complete pulmonary function tests due to myeloma related pain or fracture must have a high resolution CT scan of the chest and must also have acceptable arterial blood gases defined as P02 greater than 70.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Frits van Rhee, M.D., Ph.D.
Organizational Affiliation
UAMS
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Arkansas for Medical Sciences/MIRT
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States

12. IPD Sharing Statement

Links:
URL
http://myeloma.uams.edu
Description
Myeloma Institute for Research & Therapy website

Learn more about this trial

DTPACE Followed by Tandem Transplant With Melphalan (MEL) 200 Versus MEL/Dexamethasone/Thalidomide (DT) Platinol/Adriamycin/Etoposide (PACE) Hybrid and DTPACE Consolidation

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