NCT00081939 · REGISTRY CONDITION SEARCH

UARK 2003-33, Total Therapy III

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE2
Status at capture: COMPLETED
Registry last update: 2017-10-17

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Percentage of Participants With Progression-Free Survival (PFS) at 3 Years From Initiation of Study Treatment

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: 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.
healthy Volunteers: false
maximum Age: 75 Years
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
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.
intervention Names
Drug: Velcade
Drug: Thalidomide
label
Study Treatment
type
EXPERIMENTAL

interventions

arm Group Labels
Study Treatment
description
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.
name
Velcade
type
DRUG
arm Group Labels
Study Treatment
description
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.
name
Thalidomide
type
DRUG

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 303
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
Percentage of Participants With Progression-Free Survival (PFS) at 3 Years From Initiation of Study Treatment
time Frame
3 years

Full study description

brief Summary: 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.
detailed Description: 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.

Source references

references

citation
Ling W, Zangari M, Van Rhee F, Barlogie B, Yaccoby S. Altered mesenchymal and endothelial subsets in interstitial bone marrow and focal lesions in myeloma patients and SCID-hu mice. Haematologica. 2025 Nov 1;110(11):2740-2751. doi: 10.3324/haematol.2025.287717. Epub 2025 Jun 12.
pmid
40501401
type
DERIVED
citation
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.
pmid
40471585
type
DERIVED
citation
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.
pmid
33357481
type
DERIVED
citation
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.
pmid
27581518
type
DERIVED
citation
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.
pmid
23603914
type
DERIVED
citation
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.
pmid
23305732
type
DERIVED
citation
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.
pmid
22733020
type
DERIVED
citation
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.
pmid
22689675
type
DERIVED
citation
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.
pmid
22674807
type
DERIVED