UARK 2006-15: A Study of Tandem Transplants With or Without Bortezomib and Thalidomide

NCT ID: NCT00574080

Last Updated: 2017-11-20

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-07-31

Study Completion Date

2011-03-31

Brief Summary

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Add three drugs, bortezomib, thalidomide, and dexamethasone (VTD) to the high dose chemotherapy regimen immediately before transplant (DPACE/Melphalan) to try to improve myeloma response and acquire longer survival for participants.

Detailed Description

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Conditions

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Multiple Myeloma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A

DPACE Induction, Melphalan/DPACE Transplant 1, BEAM Transplant 2, DPACE Consolidation, Dexamethasone Maintenance with Interim dexamethasone between treatment phases

Group Type EXPERIMENTAL

Interim/Maintenance Dexamethasone

Intervention Type DRUG

20 mg Days 1-4 every 3 weeks in the interim between treatment phases and during maintenance

Induction/Consolidation Dexamethasone

Intervention Type DRUG

40 mg Days 1-4

Induction/Consolidation Cisplatin

Intervention Type DRUG

10 mg/m2 by continuous infusion Days 1-4

Induction/Consolidation Adriamycin

Intervention Type DRUG

10 mg/m2 by continuous infusion Days 1-4

InductionConsolidation Cyclophosphamide

Intervention Type DRUG

400 mg/m2 by continuous infusion Days 1-4

Induction/Consolidation Etoposide

Intervention Type DRUG

40 mg/m2 by continuous infusion Days 1-4

Induction Pegfilgrastim

Intervention Type DRUG

6 mg Days 6 and 13

Transplant 1 Dexamethasone

Intervention Type DRUG

20 mg Days -4, -3, -2, -1 and +4, +5, +6, and +7

Transplant 1 Cisplatin

Intervention Type DRUG

20 mg/m2 by continuous infusion Days -3 and -2

Transplant 1 Adriamycin

Intervention Type DRUG

20 mg/m2 by continuous infusion Days -3 and -2

Transplant 1 Cyclophosphamide

Intervention Type DRUG

800 mg/m2 by continuous infusion Days -3 and -2

Transplant 1 Etoposide

Intervention Type DRUG

80 mg/m2 by continuous infusion Days -3 and -2

Transplant 1 Melphalan

Intervention Type DRUG

50 mg/m2 Days -2 and -1

Transplant 1 and 2 Pegfilgrastim

Intervention Type DRUG

6 mg Day +6

Autologous Peripheral Blood Stem Cell Transplant (ASCT)

Intervention Type PROCEDURE

Day 0

Transplant 2 Carmustine

Intervention Type DRUG

300 mg/m2 Day -5

Transplant 2 Etoposide

Intervention Type DRUG

200 mg/m2 Days -5, -4, -3, -2

Transplant 2 Cytarabine

Intervention Type DRUG

400 mg/m2 Days -5, -4, -3, -2

Transplant 2 Melphalan

Intervention Type DRUG

140 mg/m2 Day -1

Transplant 2 Dexamethasone

Intervention Type DRUG

20 mg Days -5, -4, -3, -2, +4, +5, +6, +7

Arm B

DPACE Induction, Melphalan/DPACE + VTD Transplant 1, BEAM + VTD Transplant 2, DPACE Consolidation, Dexamethasone Maintenance with Interim dexamethasone between treatment phases

Group Type EXPERIMENTAL

Interim/Maintenance Dexamethasone

Intervention Type DRUG

20 mg Days 1-4 every 3 weeks in the interim between treatment phases and during maintenance

Induction/Consolidation Dexamethasone

Intervention Type DRUG

40 mg Days 1-4

Induction/Consolidation Cisplatin

Intervention Type DRUG

10 mg/m2 by continuous infusion Days 1-4

Induction/Consolidation Adriamycin

Intervention Type DRUG

10 mg/m2 by continuous infusion Days 1-4

InductionConsolidation Cyclophosphamide

Intervention Type DRUG

400 mg/m2 by continuous infusion Days 1-4

Induction/Consolidation Etoposide

Intervention Type DRUG

40 mg/m2 by continuous infusion Days 1-4

Induction Pegfilgrastim

Intervention Type DRUG

6 mg Days 6 and 13

Transplant 1 Dexamethasone

Intervention Type DRUG

20 mg Days -4, -3, -2, -1 and +4, +5, +6, and +7

Transplant 1 Cisplatin

Intervention Type DRUG

20 mg/m2 by continuous infusion Days -3 and -2

Transplant 1 Adriamycin

Intervention Type DRUG

20 mg/m2 by continuous infusion Days -3 and -2

Transplant 1 Cyclophosphamide

Intervention Type DRUG

800 mg/m2 by continuous infusion Days -3 and -2

Transplant 1 Etoposide

Intervention Type DRUG

80 mg/m2 by continuous infusion Days -3 and -2

Transplant 1 Melphalan

Intervention Type DRUG

50 mg/m2 Days -2 and -1

Transplant 1 and 2 Pegfilgrastim

Intervention Type DRUG

6 mg Day +6

Autologous Peripheral Blood Stem Cell Transplant (ASCT)

Intervention Type PROCEDURE

Day 0

Transplant 2 Carmustine

Intervention Type DRUG

300 mg/m2 Day -5

Transplant 2 Etoposide

Intervention Type DRUG

200 mg/m2 Days -5, -4, -3, -2

Transplant 2 Cytarabine

Intervention Type DRUG

400 mg/m2 Days -5, -4, -3, -2

Transplant 2 Melphalan

Intervention Type DRUG

140 mg/m2 Day -1

Transplant 2 Dexamethasone

Intervention Type DRUG

20 mg Days -5, -4, -3, -2, +4, +5, +6, +7

Transplant 1 and 2 Bortezomib

Intervention Type DRUG

1 mg/m2 Days -4, -1, +3, +7

Transplant 1 and 2 Thalidomide

Intervention Type DRUG

200 mg Days -4 to +5

Interventions

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Interim/Maintenance Dexamethasone

20 mg Days 1-4 every 3 weeks in the interim between treatment phases and during maintenance

Intervention Type DRUG

Induction/Consolidation Dexamethasone

40 mg Days 1-4

Intervention Type DRUG

Induction/Consolidation Cisplatin

10 mg/m2 by continuous infusion Days 1-4

Intervention Type DRUG

Induction/Consolidation Adriamycin

10 mg/m2 by continuous infusion Days 1-4

Intervention Type DRUG

InductionConsolidation Cyclophosphamide

400 mg/m2 by continuous infusion Days 1-4

Intervention Type DRUG

Induction/Consolidation Etoposide

40 mg/m2 by continuous infusion Days 1-4

Intervention Type DRUG

Induction Pegfilgrastim

6 mg Days 6 and 13

Intervention Type DRUG

Transplant 1 Dexamethasone

20 mg Days -4, -3, -2, -1 and +4, +5, +6, and +7

Intervention Type DRUG

Transplant 1 Cisplatin

20 mg/m2 by continuous infusion Days -3 and -2

Intervention Type DRUG

Transplant 1 Adriamycin

20 mg/m2 by continuous infusion Days -3 and -2

Intervention Type DRUG

Transplant 1 Cyclophosphamide

800 mg/m2 by continuous infusion Days -3 and -2

Intervention Type DRUG

Transplant 1 Etoposide

80 mg/m2 by continuous infusion Days -3 and -2

Intervention Type DRUG

Transplant 1 Melphalan

50 mg/m2 Days -2 and -1

Intervention Type DRUG

Transplant 1 and 2 Pegfilgrastim

6 mg Day +6

Intervention Type DRUG

Autologous Peripheral Blood Stem Cell Transplant (ASCT)

Day 0

Intervention Type PROCEDURE

Transplant 2 Carmustine

300 mg/m2 Day -5

Intervention Type DRUG

Transplant 2 Etoposide

200 mg/m2 Days -5, -4, -3, -2

Intervention Type DRUG

Transplant 2 Cytarabine

400 mg/m2 Days -5, -4, -3, -2

Intervention Type DRUG

Transplant 2 Melphalan

140 mg/m2 Day -1

Intervention Type DRUG

Transplant 2 Dexamethasone

20 mg Days -5, -4, -3, -2, +4, +5, +6, +7

Intervention Type DRUG

Transplant 1 and 2 Bortezomib

1 mg/m2 Days -4, -1, +3, +7

Intervention Type DRUG

Transplant 1 and 2 Thalidomide

200 mg Days -4 to +5

Intervention Type DRUG

Other Intervention Names

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Dex Dexamethasone acetate Dex Dexamethasone acetate Ara-C Velcade

Eligibility Criteria

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Inclusion Criteria

* Patients with symptomatic multiple myeloma, sensitive or refractory to at least one prior line of chemotherapy.
* Karnofsky performance score \> 60%, unless due to MM.
* Patients must be \<75 years of age at the time of registration.
* Patient must not have had a prior auto- or allotransplant.
* Patient must have signed an IRB-approved informed consent and understand the investigational nature of the study.
* Negative serology for HIV.
* Baseline biopsies and laboratory studies are to be completed within 35 days of registration, within 60 days for scans and radiological studies; patients must not have a history of severe chronic obstructive or chronic restrictive pulmonary disease. Patients must have adequate pulmonary function studies \> 50% of predicted on mechanical aspects (FEV1, FVC, etc) and diffusion capacity (DLCO) \> 50% of predicted. Patients unable to complete pulmonary function tests because of myeloma-related chest pain, must have a high resolution CT scan of the chest and must also have acceptable arterial blood gases defined as P02 greater than 70.
* Patients with recent (\< 6 months) myocardial infarction, unstable angina, difficult to control congestive heart failure, uncontrolled hypertension, or difficult to control cardiac arrhythmias are ineligible. Ejection fraction by ECHO or MUGA must be \> 40% 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.
* 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 or if the malignancy is considered much less life threatening than the myeloma.
* Pregnant or nursing women may not participate. Women of childbearing potential must have a negative pregnancy documented within one week of registration. Women/men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
* Patients must be able to receive full doses of D PACE, in the opinion of the treating investigator, with the exception that patients with creatinine clearance 30-50 ml/min will receive only 50% of the cisplatin dose.

Exclusion Criteria

* Fever or active infection requiring intravenous antibiotic, defined as fever or antibiotics within 72 hours from baseline.
* Severe renal dysfunction, defined as a creatinine \> 3mg/dl or a creatinine clearance of \< 30ml/min.
* Significant neurotoxicity, defined as grade \> 3 neurotoxicity per NCI Common Toxicity Criteria (See Appendix).
* Platelet count \< 100,000/mm\^3, or ANC \< 1,000/μl
* POEMS Syndrome.
* Clinically significant hepatic dysfunction as noted by direct bilirubin or AST \>3 times the upper normal limit or clinically significant concurrent hepatitis.
* New York Hospital Association (NYHA) Class III or Class IV heart failure.
* Myocardial infarction within the last 6 months.
* Patients with a history of treatment for clinically significant ventricular cardiac arrhythmias.
* Poorly-controlled hypertension, diabetes mellitus, or other serious medical illness or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol.
* Prior adriamycin exposure \>450 mg/m\^2
* Prior exposure to thalidomide which resulted in severe toxicity requiring drug discontinuation.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Arkansas

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Frits van Rhee, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Arkansas

Locations

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University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

Countries

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United States

Other Identifiers

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2006-15

Identifier Type: -

Identifier Source: org_study_id