Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2
303 participants
INTERVENTIONAL
2004-01-31
2014-09-30
Brief Summary
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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.
Detailed Description
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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.
Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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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.
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.
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.
Interventions
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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.
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.
Eligibility Criteria
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Inclusion Criteria
* 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.
Exclusion Criteria
* 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.
18 Years
75 Years
ALL
No
Sponsors
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University of Arkansas
OTHER
Responsible Party
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Principal Investigators
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Bart Barlogie, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
UAMS
Locations
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University of Arkansas for Medical Sciences/MIRT
Little Rock, Arkansas, United States
Countries
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References
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Al Hadidi S, Ababneh OE, Schinke CD, Thanendrarajan S, Siegel ER, Bailey C, Smith R, Panozzo SB, Zangari M, Tricot G, Shaughnessy JD Jr, Zhan F, Sawyer J, Barlogie B, van Rhee F. Long-Term Follow-Up of Patients With Multiple Myeloma Treated on Earlier Total Therapy Protocols: A Secondary Analysis of 3 Clinical Trials. JAMA Oncol. 2025 Aug 1;11(8):910-915. doi: 10.1001/jamaoncol.2025.1394.
Pawlyn C. High-risk myeloma: a challenge to define and to determine the optimal treatment. Lancet Haematol. 2021 Jan;8(1):e4-e6. doi: 10.1016/S2352-3026(20)30361-6. Epub 2020 Dec 22. No abstract available.
Vatsveen TK, Sponaas AM, Tian E, Zhang Q, Misund K, Sundan A, Borset M, Waage A, Brede G. Erythropoietin (EPO)-receptor signaling induces cell death of primary myeloma cells in vitro. J Hematol Oncol. 2016 Aug 31;9(1):75. doi: 10.1186/s13045-016-0306-x.
Usmani SZ, Sawyer J, Rosenthal A, Cottler-Fox M, Epstein J, Yaccoby S, Sexton R, Hoering A, Singh Z, Heuck CJ, Waheed S, Chauhan N, Johann D, Abdallah AO, Muzaffar J, Petty N, Bailey C, Crowley J, van Rhee F, Barlogie B. Risk factors for MDS and acute leukemia following total therapy 2 and 3 for multiple myeloma. Blood. 2013 Jun 6;121(23):4753-7. doi: 10.1182/blood-2012-11-466961. Epub 2013 Apr 19.
Usmani SZ, Mitchell A, Waheed S, Crowley J, Hoering A, Petty N, Brown T, Bartel T, Anaissie E, van Rhee F, Barlogie B. Prognostic implications of serial 18-fluoro-deoxyglucose emission tomography in multiple myeloma treated with total therapy 3. Blood. 2013 Mar 7;121(10):1819-23. doi: 10.1182/blood-2012-08-451690. Epub 2013 Jan 10.
Waheed S, Mitchell A, Usmani S, Epstein J, Yaccoby S, Nair B, van Hemert R, Angtuaco E, Brown T, Bartel T, McDonald J, Anaissie E, van Rhee F, Crowley J, Barlogie B. Standard and novel imaging methods for multiple myeloma: correlates with prognostic laboratory variables including gene expression profiling data. Haematologica. 2013 Jan;98(1):71-8. doi: 10.3324/haematol.2012.066555. Epub 2012 Jun 24.
Usmani SZ, Heuck C, Mitchell A, Szymonifka J, Nair B, Hoering A, Alsayed Y, Waheed S, Haider S, Restrepo A, Van Rhee F, Crowley J, Barlogie B. Extramedullary disease portends poor prognosis in multiple myeloma and is over-represented in high-risk disease even in the era of novel agents. Haematologica. 2012 Nov;97(11):1761-7. doi: 10.3324/haematol.2012.065698. Epub 2012 Jun 11.
Usmani SZ, Sexton R, Hoering A, Heuck CJ, Nair B, Waheed S, Al Sayed Y, Chauhan N, Ahmad N, Atrash S, Petty N, van Rhee F, Crowley J, Barlogie B. Second malignancies in total therapy 2 and 3 for newly diagnosed multiple myeloma: influence of thalidomide and lenalidomide during maintenance. Blood. 2012 Aug 23;120(8):1597-600. doi: 10.1182/blood-2012-04-421883. Epub 2012 Jun 6.
Related Links
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Click here for more information about UAMS
Other Identifiers
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UARK 2003-33
Identifier Type: -
Identifier Source: org_study_id