Multiple MyelomaPhase 3TT4BNCT00734877
UARK 2013-13, Total Therapy 4B - Formerly 2008-01 - A Phase III Trial for Low Risk Myeloma
A Phase 3 study testing M-VTD-PACE and TT3-LITE Regimen (L-TT3) in people with Multiple Myeloma, run by University of Arkansas at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- M-VTD-PACE and TT3-LITE Regimen (L-TT3)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 382 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2008to Sep 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 13Show fewer
- 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.
Who cannot join
- 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.
Show all 13Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Arkansas for Medical Sciences, Myeloma Institute for Research and Therapy
Little Rock, Arkansas, 72205
About this study
Official title: UARK 2013-13, Total Therapy 4B - Formerly 2008-01 - A Phase III Trial for Low Risk Myeloma Ages 65 and Under: A Trial Enrolling Subjects to Standard Total Therapy 3 (S-TT3)
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.
Read the detailed description
The major treatment-related toxicities in TT3 pertained to the high-dose melphalan 200mg/m2 (MEL200)-based tandem transplant approach, consisting of mucosal and other toxicities.
For the TT4 trial, we are proposing to compare standard TT3 (S-TT3) to TT3-Lite (L-TT3). L-TT3 will employ various strategies aimed at improving the therapeutic Index of S-TT3 by reducing toxicities while maintaining the superior results reported for S-TT3 in terms of frequency and duration of CR, EFS, and. The following strategies will be utilized in L-TT3:
- Applying only 1 instead of 2 cycles of induction and consolidation therapy prior to and after tandem transplant. This is supported by the well known association between prior exposure to mucotoxic therapies4, 5 and worse post-transplant mucositis, particularly when etoposide is used in the mobilizing regimen6 such as in VDTPACE.
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
- Being tested
- M-VTD-PACE, TT3-LITE Regimen (L-TT3)
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
M-VTD-PACEDrug
Also called Melphalan, Velcade, Thalidomide, Dexamethasone
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.
TT3-LITE Regimen (L-TT3)Drug
Also called Velcade (bortezomib), Melphalan, Dexamethasone, Thalidomide
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: M-VTD-PACE |
| ARM B | Experimental | The TT3-LITE Regimen (L-TT3) will employ only 1 cycle of induction therapy with MVTD- PACE Receives: Drug: TT3-LITE Regimen (L-TT3) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival rate
Percentage of subjects without disease progression (per IMWG definition) at 3 years from initial registration
Measured: 3 years from study enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2008 (estimated)
- Study startJul 2008
- Primary completionSep 2027 (estimated)
- Study completionSep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by University of ArkansasThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 382 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Arkansas
- Sponsor type
- University, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Responsible party
- Sponsor
- Investigators
- Maurizio Zangari, MD, Principal investigator, UAMSMaurizio Zangari, MD, Study director, UAMS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00734877
- Sponsor's protocol ID
- 103668
- Acronym
- TT4B
- Status last verified
- May 2026
- First submitted
- 12 Aug 2008
- Last updated
- 22 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 40501401Davies 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.
PubMed 29567784Usmani 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.
PubMed 22689675
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- UARK 2013-13, Total Therapy 4B - Formerly 2008-01 - A Phase III Trial for Low Risk Myeloma Ages 65 and Under: A Trial Enrolling Subjects to Standard Total Therapy 3 (S-TT3)
- ClinicalTrials.gov ID
- NCT00734877
- Acronym / sponsor ID
- TT4B / 103668
- Conditions
- Multiple Myeloma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 382 participants (actual)
- Lead sponsor
- University of ArkansasUniversity, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Study start
- Jul 2008 (actual)
- Primary completion
- Sep 2027 (estimated)
- Study completion
- Sep 2028 (estimated)
- First posted
- 14 Aug 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The major treatment-related toxicities in TT3 pertained to the high-dose melphalan 200mg/m2 (MEL200)-based tandem transplant approach, consisting of mucosal and other toxicities.
For the TT4 trial, we are proposing to compare standard TT3 (S-TT3) to TT3-Lite (L-TT3). L-TT3 will employ various strategies aimed at improving the therapeutic Index of S-TT3 by reducing toxicities while maintaining the superior results reported for S-TT3 in terms of frequency and duration of CR, EFS, and. The following strategies will be utilized in L-TT3:
- Applying only 1 instead of 2 cycles of induction and consolidation therapy prior to and after tandem transplant. This is supported by the well known association between prior exposure to mucotoxic therapies4, 5 and worse post-transplant mucositis, particularly when etoposide is used in the mobilizing regimen6 such as in VDTPACE.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ARM A | Active comparator | Drug: M-VTD-PACEThe 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. |
| ARM B | Experimental | Drug: TT3-LITE Regimen (L-TT3)The TT3-LITE Regimen (L-TT3) will employ only 1 cycle of induction therapy with MVTD- PACE |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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:
- 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.
Key exclusion criteria (13 listed)
- High risk disease defined by high-risk gene array features as determined by any of the following:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| M-VTD-PACEAlso: Melphalan, Velcade, Thalidomide, Dexamethasone2 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 | ARM A |
| TT3-LITE Regimen (L-TT3)Also: Velcade (bortezomib), Melphalan, Dexamethasone, ThalidomideThe 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. | Drug | ARM B |
Primary outcome
Progression-free survival rate
Time frame: 3 years from study enrollment
Percentage of subjects without disease progression (per IMWG definition) at 3 years from initial registration
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2026.
- Derived from this study: PubMed 40501401Ling 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.
- Derived from this study: PubMed 29567784Davies 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.
- Derived from this study: PubMed 22689675Usmani 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.
- UAMS Myeloma CenterLink provided by the sponsor.
Related trials for Multiple Myeloma
RecruitingObservational study
Family Study of Lymphoproliferative Disorders
Lymphoma, Non-Hodgkin, Leukemia, Lymphocytic, Chronic, B-Cell
RecruitingPhase 1
ELEVATE-MM: Elotuzumab, Iberdomide and Dexamethasone Post Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma
Myeloma, Multiple Myeloma
Not yet recruiting
A Randomized Controlled Trial of a Wearable Core Body Temperature Sensor Versus Standard Temperature Monitoring for Early Detection of Cytokine Release Syndrome in Patients Undergoing CAR T-Cell Therapy in an Outpatient Setting
Myeloma
RecruitingObservational study
Long-term Evaluation and Follow-up Care of Patients Treated With Stem Cell Transplants
Graft-versus-leukemia, Graft vs Host Disease
Not yet recruiting
Monitoring for CardioToxicity Using WeArable deVices While Undergoing cancEr Treatments (MCT-WAVE)
Cardiotoxicity, Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Maurizio Zangari, MD principal investigator
UAMS
Maurizio Zangari, MD study director
UAMS
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing M-VTD-PACE and TT3-LITE Regimen (L-TT3) in people with Multiple Myeloma, run by University of Arkansas at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 22 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival rate (time frame: 3 years from study enrollment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00734877, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2026.