Clinical Trials /

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

NCT00734877

Description:

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.

Related Conditions:
  • Multiple Myeloma
  • Smoldering Plasma Cell Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 103668
  • NCT ID: NCT00734877

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
M-VTD-PACEMelphalan, Velcade, Thalidomide, Dexamethasone, Cisplatin, Adriamycin, Cyclophosphamide, EtoposideARM A
TT3-LITE Regimen (L-TT3)Velcade (bortezomib), Melphalan, Dexamethasone, Thalidomide, Cisplatin, Adriamycin, Cyclophosphamide, EtoposideARM B

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
ARM AActive ComparatorThe 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.
  • M-VTD-PACE
ARM BExperimentalThe TT3-LITE Regimen (L-TT3) will employ only 1 cycle of induction therapy with MVTD- PACE
  • TT3-LITE Regimen (L-TT3)

Eligibility Criteria

        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.
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival rate
Time Frame:3 years from study enrollment
Safety Issue:
Description:Percentage of subjects without disease progression (per IMWG definition) at 3 years from initial registration

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Arkansas

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