UARK 2013-13, Total Therapy 4B - Formerly 2008-01 - A Phase III Trial for Low Risk Myeloma (TT4B)

August 7, 2023 updated by: University of Arkansas

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

382

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • University of Arkansas for Medical Sciences, Myeloma Institute for Research and Therapy

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.
  • 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.

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: ARM A
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
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.
Other Names:
  • Velcade
  • Dexamethasone
  • Cisplatin
  • Cyclophosphamide
  • Adriamycin
  • Thalidomide
  • Etoposide
  • Melphalan
Experimental: ARM B
The TT3-LITE Regimen (L-TT3) will employ only 1 cycle of induction therapy with MVTD- PACE
Drug: TT3-LITE Regimen (L-TT3)
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.
Other Names:
  • Dexamethasone
  • Cisplatin
  • Cyclophosphamide
  • Adriamycin
  • Thalidomide
  • Etoposide
  • Melphalan
  • Velcade (bortezomib)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
3 years from study enrollment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Arkansas

Collaborators

Millennium Pharmaceuticals, Inc.

Investigators

  • Principal Investigator: Maurizio Zangari, MD, UAMS
  • Study Director: Maurizio Zangari, MD, UAMS

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2008

Primary Completion (Estimated)

September 1, 2024

Study Completion (Estimated)

September 1, 2024

Study Registration Dates

First Submitted

August 12, 2008

First Submitted That Met QC Criteria

August 13, 2008

First Posted (Estimated)

August 14, 2008

Study Record Updates

Last Update Posted (Actual)

August 9, 2023

Last Update Submitted That Met QC Criteria

August 7, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 103668

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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