UARK 2003-33, Total Therapy III

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Arkansas
ClinicalTrials.gov Identifier:
NCT00081939
First received: April 27, 2004
Last updated: September 18, 2015
Last verified: September 2015

April 27, 2004
September 18, 2015
January 2004
September 2014   (final data collection date for primary outcome measure)
Progression-Free Survival (PFS) at 3 Years From Initiation of Study Treatment. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
In patients with no confirmed Partial Response, Near Complete Response, or Complete Response, progression was defined as a >25% increase from baseline in myeloma protein production or other signs of disease progression such as hypercalcemia, etc. PFS was measured as the time from initial registration to progression/relapse of disease or death from any cause.
  • To determine, in a historical comparison with TT II (Thalidomide arm), whether two cycles of VDTPACE induction (instead of four induction cycles in TT II) followed by more timely MEL 200-based transplant with DEX + THAL between transplants can:
  • 1.1.1 Increase the CR frequency from 50% to 60% at 18 months from initiation of therapy;
  • 1.1.2 Increase > n-CR rate pre-transplant #1 from 20% to 40%;
  • 1.1.3 Raise 2-year EFS rates from 55% to 75% in patients with CA and from 80% to 95%, in patients without CA.
Complete list of historical versions of study NCT00081939 on ClinicalTrials.gov Archive Site
Not Provided
  • 1.2 To determine whether bortezomib can be safely incorporated into well tested DT-PACE induction (VDT-PACE) with PBSC mobilization, DT-PACE consolidation after MEL 200 tandem transplant and into DEX + THAL maintenance.
  • 1.2.1 To evaluate whether increasing dosing frequency of bortezomib 1.0 mg/m2 compromises PBSC procurement after DTPACE with a target yield of > 20 x 106 CD34 cells/kg.
  • 1.2.2 To evaluate whether DEX + THAL can be administered during ongoing hematopoietic recovery after first and second autotransplant without compromising subsequent VDTPACE tolerance.
Not Provided
Not Provided
 
UARK 2003-33, Total Therapy III
A Phase 2 Study Incorporating Bone Marrow Microenvironment (ME) Co-Targeting Bortezomib Into Tandem Melphalan-Based Autotransplants With DT PACE for Induction/Consolidation and Thalidomide + Dexamethasone for Maintenance

There have been two previous Total Therapy studies for multiple myeloma (MM) at the Myeloma Institute for Research and Therapy (MIRT): Total Therapy I (from 1989 through 1994) and Total Therapy II (from 1996 to 2004). Results have shown that patients treated on these studies had better outcomes (meaning patients have lived longer and had better responses to treatment) when compared to patients treated with standard chemotherapy.

With this new study, Total Therapy III, researchers will take what they have learned from the first two studies and add new treatment strategies to try to improve the outcomes even more, especially for patients with chromosome abnormalities.

1.1 To determine, in a historical comparison with TT II (Thalidomide arm), whether two cycles of VDTPACE induction (instead of four induction cycles in TT II) followed by more timely MEL 200-based transplant with DEX + THAL between transplants can:

1.1.1 Increase the CR frequency from 50% to 60% at 18 months from initiation of therapy;

1.1.2 Increase > n-CR rate pre-transplant #1 from 20% to 40%;

1.1.3 Raise 2-year EFS rates from 55% to 75% in patients with CA and from 80% to 95%, in patients without CA.

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Multiple Myeloma
  • Drug: Velcade
    Two cycles of induction on days 1,4,8,11 at 1.0mg/m^2. Two cycles of consolidation on days 1,4,8,11 at 1.0mg/m^2. Maintenance year one 1.0mg/m^2 1,4,8,11 q 28 days.
  • Drug: Thalidomide
    Two cycles of VDTPACE 200mg thal days 4-7(cycle 1)and days 1-4 cycle 2 interim Thal 50mg qd between VTDPACE cycles and between cycle 2 and transplant. Thal 100mg between transplants d/c 7 days prior to each transplant. Consolidation therapy cycles 3 and 4 VDTPACE 200mg days 1-4 both cycles. Interim maintenance to maintenance 100mg qd. Maintenance year 1 thal 100mg qd. Maintenance years 2 and 3 Thal 100mg qd.
Experimental: Study Treatment
Two cycles of VDTPACE induction (Velcade days 1, 4, 8, and 11; DTPACE days 4-7) with interim thalidomide (50 mg QD) + Dex (20 mg QD x 4 days every 21 days) following each cycle. Induction followed by single or tandem MEL200 transplant (MEL140 mg/m2 for subjects > 70 years of age) with interim thalidomide (100mg QD) + Dex (20 mg QD x 4 days every 21 days) following each transplant. Transplants followed by two cycles of VDTPACE consolidation (Velcade days 1, 4, 8, and 11; DTPACE days 1-4) with interim thalidomide (100mg QD) + Dex (20 mg QD x 4 days every 21 days) following each cycle of VDTPACE. Consolidation followed by 3 years of maintenance therapy with VDT (velcade 1.0 mg/m2 days 1, 4, 8, 11 q 28 days; Thal 100 mg QD; and Dex 20mg days 1-4 and 8-11 q 28 days) during Year 1 and TD (Thal 100 mg QD and Dex 20 mg days 1-4, q 28 days) or VTD (velcade 1.0 mg/m2 weekly, Thal 100 mg QD, and Dex 20 mg weekly) during Years 2 and 3.
Interventions:
  • Drug: Velcade
  • Drug: Thalidomide

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
303
September 2014
September 2014   (final data collection date for primary outcome measure)

Induction Inclusion Criteria:

  • Patients must have newly diagnosed active MM requiring treatment. Patients with a previous history of smoldering myeloma will be eligible if there is evidence of progressive disease requiring chemotherapy.
  • Protein criteria must be present (quantifiable M-component of IgG, IgA, IgD, or IgE and/or urinary kappa or lambda light chain or Bence Jones protein) in order to evaluate response. Non-secretory patients are eligible provided the patient has > 20% plasmacytosis or multiple (>3) focal plasmacytomas on MRI or diffuse hyperintense signal on STIR images in the absence of hematopoietic growth factors.
  • Patients must have received no more than one cycle of prior chemotherapy for this disease. Patients may have received prior radiotherapy provided approval has been obtained by the Principal Investigator.
  • Patients must be < or = 75 years of age at the time of initial registration.
  • Ejection fraction by ECHO or MUGA >40% performed within 60 days prior to registration.
  • Patients must have adequate pulmonary function studies > or = 50% of predicted on mechanical aspects (FEV1, FVC, etc) and diffusion capacity (DLCO) > or =50% of predicted, within 60 days of registration. If the patient is unable to complete pulmonary function tests due to MM related pain or condition, there must be a pulmonary consult documenting that the patient is a candidate for high dose therapy.
  • Patients must have a performance status of 0-2 based on SWOG criteria. Patients with a poor performance status (3-4), based solely on bone pain, will be eligible.
  • All patients must be informed of the investigational nature of this study and must have signed an IRB-approved informed consent in accordance with institutional and federal guidelines.

Induction Exclusion Criteria:

  • Platelet count < 30 x 10^9/L, unless myeloma-related
  • ANC < 1.0 X 10^9/L, unless myeloma-related
  • Grade > or =2 peripheral neuropathy
  • Hypersensitivity to bortezomib, boron, or mannitol
  • Uncontrolled diabetes.
  • Recent (< or =6 months) myocardial infarction, unstable angina, difficult to control congestive heart failure, uncontrolled hypertension, or difficult to control cardiac arrhythmias.
  • Evidence of chronic obstructive or chronic restrictive pulmonary disease.
  • Prior malignancy, 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.
  • Patients must not have significant co-morbid medical conditions or uncontrolled life threatening infection.
  • Pregnant or nursing women. Women of child-bearing potential must have a negative pregnancy test documented within one week of registration. Women and men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
Both
18 Years to 75 Years   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00081939
UARK 2003-33
Yes
Not Provided
Not Provided
University of Arkansas
University of Arkansas
Not Provided
Principal Investigator: Bart Barlogie, MD, PhD UAMS
University of Arkansas
September 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP