UARK 2013-13, Total Therapy 4B - Formerly 2008-01 - A Phase III Trial for Low Risk Myeloma

NCT00734877 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: 103668
• Study Type: interventional
• Target: 382
• Locations: 1 country
• Sites: 1

Brief Summary

Toward improving the therapeutic index of standard TT3 (S-TT3), the investigators will employ a randomized Phase III trial design to determine whether S-TT3 treatment-related toxicities can be reduced by 50% in TT3-Lite (L-TT3). Note: Randomization has been discontinued and accrual is closed to the L-TT3 arm. This trial is currently enrolling as a single-arm trial for patients to receive S-TT3.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Progression-free survival rate

  Percentage of subjects without disease progression (per IMWG definition) at 3 years from initial registration

  3 years from study enrollment

Study Arms (2)

ARM A

ACTIVE COMPARATOR

The standard TT3 Regimen (S-TT3) will consist of 2 cycles of induction therapy with M-VTD-PACE and PBSC collection after the 1st cycle. MEL-based tandem transplant will be administered 6 weeks to 3 months apart, applying single dose MEL 200 mg/m2 with adjustments for age and renal function. Consolidation will consist of 2 cycles of dose-reduced VTD-PACE. Maintenance treatment will employ VRD for 3 years.

Drug: M-VTD-PACE

ARM B

EXPERIMENTAL

The TT3-LITE Regimen (L-TT3) will employ only 1 cycle of induction therapy with MVTD- PACE

Drug: TT3-LITE Regimen (L-TT3)

Interventions

M-VTD-PACE DRUG

2 cycles of induction therapy with M-VTD-PACE and PBSC collection after the 1st cycle. MEL-based tandem transplant will be administered 6 weeks to 3 months apart, applying single dose MEL 200 mg/m2 with adjustments for age and renal function. Consolidation will consist of 2 cycles of dose-reduced VTD-PACE. Maintenance treatment will employ VRD for 3 years.

Also known as: Melphalan, Velcade, Thalidomide, Dexamethasone, Cisplatin, Adriamycin, Cyclophosphamide, Etoposide

ARM A

TT3-LITE Regimen (L-TT3) DRUG

The TT3-LITE Regimen (L-TT3) will employ only 1 cycle of induction therapy with MVTD-PACE and, as in S-TT3, PBSC collection following recovery from this one and only induction treatment. MEL-based tandem transplant will be administered 6 weeks to 3 months apart, applying fractionated MEL200mg/m2 in 4 successive daily fractions of 50mg/m2 (MEL50 x 4) with addition of VTD with adjustments for age and renal function. Consolidation will consist of only 1 cycle of dose-reduced VTD-PACE. Maintenance treatment will employ VRD for 3 years.

Also known as: Velcade (bortezomib), Melphalan, Dexamethasone, Thalidomide, Cisplatin, Adriamycin, Cyclophosphamide, Etoposide

ARM B

Eligibility Criteria

• Age: 18 Years - 75 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.
• Patients must be either untreated or have not had more than one cycle of systemic MM therapy, excluding bisphosphonates and localized radiation.
• Participants must have low-risk disease, as defined by any of the following:
• GEP risk score of \< 0.66
• lack of GEP-defined TP53 deletion (Affymetrix signal \<727)
• No metaphase based abnormalities of 1q or 1p
• LDH \<360 U/L Rule out hemolysis, infection, and contact PI for Clarification
• Zubrod ≤ 2, unless solely due to symptoms of MM-related bone disease.
• Patients must be at least 18 years of age and not older than 75 years of age at the time of registration.
• Participants must have preserved renal function as defined by a serum creatinine level of \< 3 mg/dL.
• Participants must have an ejection fraction by ECHO or MUGA ≥ 40%
• Patients must have adequate pulmonary function studies \> 50% of predicted on mechanical aspects (FEV1, FVC, etc) and diffusion capacity (DLCO) \> 50% of predicted. 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 signed an IRB-approved informed consent indicating their understanding of the proposed treatment and understanding that the protocol has been approved by the IRB.

You may not qualify if:

• High risk disease defined by high-risk gene array features as determined by any of the following:
• GEP risk score of ≥ 0.66 or
• Presence of GEP-defined TP53 deletion, or
• Presence of abnormalities of chromosome 1 (amp1q, del 1p).
• 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.
• Platelet count \< 30 x 109/L, unless myeloma-related.
• Grade \> 2 peripheral neuropathy.
• Hypersensitivity to bortezomib, boron, or mannitol.
• 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
• 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.

Sponsors & Collaborators

• University of Arkansas: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (1)

University of Arkansas for Medical Sciences, Myeloma Institute for Research and Therapy

Little Rock, Arkansas, 72205, United States

Location

Related Publications (3)

• 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 DERIVED

• Davies FE, Rosenthal A, Rasche L, Petty NM, McDonald JE, Ntambi JA, Steward DM, Panozzo SB, van Rhee F, Zangari M, Schinke CD, Thanendrarajan S, Walker B, Weinhold N, Barlogie B, Hoering A, Morgan GJ. Treatment to suppression of focal lesions on positron emission tomography-computed tomography is a therapeutic goal in newly diagnosed multiple myeloma. Haematologica. 2018 Jun;103(6):1047-1053. doi: 10.3324/haematol.2017.177139. Epub 2018 Mar 22.

  PMID: 29567784 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

Related Links

• UAMS Myeloma Center

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Melphalan; Bortezomib; Thalidomide; Dexamethasone; Cisplatin; Doxorubicin; 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)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; 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; Chlorine Compounds; Nitrogen Compounds; Platinum Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Phosphoramides; Organophosphorus Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides

Study Officials

• Maurizio Zangari, MD

  UAMS

  PRINCIPAL INVESTIGATOR

• Maurizio Zangari, MD

  UAMS

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: August 12, 2008
• First Posted: August 14, 2008
• Study Start: July 1, 2008
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2027
• Last Updated: June 29, 2025

Record last verified: 2025-06

Locations

US (1)