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

Multiple Myeloma Clinical Trial

Official title:

UARK 2006-15: A Phase III Randomized Study of Tandem Transplants With or Without Bortezomib (Velcade) and Thalidomide (Thalomid) to Evaluate Its Effect on Response Rate and Durability of Response in Multiple Myeloma Patients

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00574080
• Other study ID #: 2006-15
• Status: Terminated
• Phase: Phase 3
• First received: December 12, 2007
• Last updated: October 17, 2017
• Start date: July 2006
• Est. completion date: March 2011

Study information

• Verified date: October 2017
• Source: University of Arkansas
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 20
• Est. completion date: March 2011
• Est. primary completion date: March 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Interim/Maintenance Dexamethasone
20 mg Days 1-4 every 3 weeks in the interim between treatment phases and during maintenance
• Induction/Consolidation Dexamethasone
40 mg Days 1-4
• Induction/Consolidation Cisplatin
10 mg/m2 by continuous infusion Days 1-4
• Induction/Consolidation Adriamycin
10 mg/m2 by continuous infusion Days 1-4
• InductionConsolidation Cyclophosphamide
400 mg/m2 by continuous infusion Days 1-4
• Induction/Consolidation Etoposide
40 mg/m2 by continuous infusion Days 1-4
• Induction Pegfilgrastim
6 mg Days 6 and 13
• Transplant 1 Dexamethasone
20 mg Days -4, -3, -2, -1 and +4, +5, +6, and +7
• Transplant 1 Cisplatin
20 mg/m2 by continuous infusion Days -3 and -2
• Transplant 1 Adriamycin
20 mg/m2 by continuous infusion Days -3 and -2
• Transplant 1 Cyclophosphamide
800 mg/m2 by continuous infusion Days -3 and -2
• Transplant 1 Etoposide
80 mg/m2 by continuous infusion Days -3 and -2
• Transplant 1 Melphalan
50 mg/m2 Days -2 and -1
• Transplant 1 and 2 Pegfilgrastim
6 mg Day +6

Procedure:
• Autologous Peripheral Blood Stem Cell Transplant (ASCT)
Day 0

Drug:
• Transplant 2 Carmustine
300 mg/m2 Day -5
• Transplant 2 Etoposide
200 mg/m2 Days -5, -4, -3, -2
• Transplant 2 Cytarabine
400 mg/m2 Days -5, -4, -3, -2
• Transplant 2 Melphalan
140 mg/m2 Day -1
• Transplant 2 Dexamethasone
20 mg Days -5, -4, -3, -2, +4, +5, +6, +7
• Transplant 1 and 2 Bortezomib
1 mg/m2 Days -4, -1, +3, +7
• Transplant 1 and 2 Thalidomide
200 mg Days -4 to +5

Locations

Country	Name	City	State
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas

Sponsors (1)

Lead Sponsor	Collaborator
University of Arkansas

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event Free Survival	Time from study registration until disease progression or death.	Up to 3 years 8 months