UARK 2006-66, Total Therapy 3B: An Extension of UARK 2003-33 Total Therapy

NCT00572169 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: 72023
• Study Type: interventional
• Target: 177
• Locations: 1 country
• Sites: 1

Brief Summary

With this study - Total Therapy IIIB - researchers are extending the findings of Total Therapy III based what they have learned from the first two studies (Total Therapy I and II), with new research strategies designed to explore why chromosome abnormalities found in persons with multiple myeloma affect the outcome of drug therapy used in this disease."

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• To find out if outcomes of participants in this study will be better when compared to individuals who participated in Total Therapy II, especially those with chromosome abnormalities.

  48 months

Secondary Outcomes (1)

• To find out if outcomes and incidence of toxicities of participants in this study will be better when compared to individuals who participated in Total Therapy III.

  48 months

Study Arms (1)

VDTPACE

EXPERIMENTAL

Velcade, Dexamethasone, Thalidomide, Cisplatinin, Adriamycin, Cyclophosphamide and Etoposide

Drug: Velcade; Drug: Thalidomide; Drug: Dexamethasone; Drug: Adriamycin; Drug: Cisplatin; Drug: Cyclophosphamide; Drug: Etoposide

Interventions

Velcade DRUG

Will be given in central venous catheter

Also known as: Bortezomib, PS-341

VDTPACE

Thalidomide DRUG

Capsule taken by mouth

Also known as: Thalomid

VDTPACE

Dexamethasone DRUG

A pill taken by mouth

Also known as: Decadron, NSC-34521

VDTPACE

Adriamycin DRUG

Given into the vein (IV) by a continuous infusion through a central catheter

Also known as: Doxorubicin, NSC-123127

VDTPACE

Cisplatin DRUG

Given into the vein (IV) by a continuous infusion through a central catheter

Also known as: Cis-diamminedichloroplatinum [CDDP], Platinol, NSC-119875

VDTPACE

Cyclophosphamide DRUG

Given into the vein (IV) by a continuous infusion through a central catheter

Also known as: Cytoxan, NSC-26271

VDTPACE

Etoposide DRUG

Given into the vein (IV) by a continuous infusion through a central catheter

Also known as: VP-16), Vepesid®, Ethylidene-Lignan P., NSC-141540

VDTPACE

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 serum M-component of IgG, IgA, IgD, or IgE; urinary kappa or lambda light chain; or serum free light chain (SFLC) levels in order to evaluate response. Non-secretory patients are eligible provided the patient has \> 20% plasmacytosis OR multiple (\>3) focal plasmacytomas or focal lesions 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 or one month of prior chemotherapy for this disease. Patients may have received prior radiotherapy provided approval has been obtained by the Principal Investigator.
• Patients must be \<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 \> 50% of predicted on mechanical aspects (FEV1, FVC, etc) and diffusion capacity (DLCO) \> 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, exception may be granted if the principal investigator documents 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.

You may not qualify if:

• Platelet count \< 30 x 109/L, unless myeloma-related.
• Grade \> 2 peripheral neuropathy.
• Hypersensitivity to bortezomib, boron, or mannitol.
• Uncontrolled diabetes.
• Recent (\< 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.
• Patients must not have light chain deposition disease or creatinine \> 3 mg/dl
• Patients must not have 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 not received treatment for one year prior to enrollment. Other cancers will only be acceptable if the patient's life expectancy exceeds five 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.

Sponsors & Collaborators

• University of Arkansas: lead

Study Sites (1)

University of Arkansas for Medical Sciences/Myeloma Institute

Little Rock, Arkansas, 72205, United States

Location

Related Publications (6)

• Al Hadidi S, Ababneh OE, Schinke CD, Thanendrarajan S, Bailey C, Smith R, Panozzo S, Alapat D, Cottler-Fox M, Tricot G, Shaughnessy JD Jr, Zhan F, Sawyer J, Barlogie B, Zangari M, van Rhee F. Three years of maintenance with VRD in multiple myeloma: results of total therapy IIIB with a 15-year follow-up. Blood Adv. 2024 Feb 13;8(3):703-707. doi: 10.1182/bloodadvances.2023011601.

  PMID: 38052037 DERIVED

• 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 DERIVED

• 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 DERIVED

• 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 DERIVED

• 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 DERIVED

• 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 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Bortezomib; Thalidomide; Dexamethasone; Calcium Dobesilate; Doxorubicin; Cisplatin; Cyclophosphamide; Etoposide

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Aminoglycosides; Glycosides; Carbohydrates; Chlorine Compounds; Nitrogen Compounds; Platinum Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides

Study Officials

• Gareth Morgan, MD, PhD

  UAMS Myeloma Institute for Research and Therapy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2007
• First Posted: December 12, 2007
• Study Start: November 1, 2006
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: February 5, 2026

Record last verified: 2026-02

Locations

US (1)