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S0833, Modified Total Therapy 3 (TT3) for Newly Diagnosed Patients With Multiple Myeloma (MM): A Phase II SWOG Trial for Patients Aged ≤ 65 Years


Phase 2
18 Years
65 Years
Not Enrolling
Both
Multiple Myeloma, Plasma Cell Myeloma

Thank you

Trial Information

S0833, Modified Total Therapy 3 (TT3) for Newly Diagnosed Patients With Multiple Myeloma (MM): A Phase II SWOG Trial for Patients Aged ≤ 65 Years


OBJECTIVES:

Primary

- To assess progression-free survival (PFS) at 3 years in patients with newly diagnosed
multiple myeloma (MM) treated with modified Total Therapy 3 (TT3).

Secondary

- To estimate the frequency and severity of toxicities associated with this treatment
strategy in these patients.

Correlative

- To perform gene expression profiling on CD138+ purified MM cells and unseparated bone
marrow biopsy samples to identify the bone marrow micro-environment signature.

- To determine whether the 70-gene model, developed in the Arkansas Total Therapy 2 (TT2)
and validated in the Arkansas TT3 study, also applies to the cooperative group setting.

- Determine whether the novel finding in TT3 of the prognostically favorable suppression
of a micro-environment-associated gene, MAG1, also applies to the cooperative group
setting.

- Once in complete remission, determine whether the MAG signatures can return to a normal
individual's signature as an indication of profound tumor cytoreduction with durable
PFS.

OUTLINE: This is a multicenter study.

- Induction therapy: Patients receive bortezomib IV on days 1, 4, 8, and 11; oral
thalidomide and oral dexamethasone on days 1-4; and cisplatin IV continuously,
doxorubicin hydrochloride IV continuously, cyclophosphamide IV continuously, and
etoposide IV continuously on days 1-4.

- Peripheral blood stem cell (PBSC) collection: Beginning within 2 months after
completion of induction therapy, patients undergo PBSC collection until an adequate
number of cells are collected. Patients with persistent disease after completion of
induction therapy proceed to bridging therapy after adequate stem cells are collected.
Patients not requiring bridging therapy proceed directly to transplant.

- Bridging therapy: Patients receive oral thalidomide on days 1-21 and oral dexamethasone
on days 1, 8, and 15. Treatment repeats every 21 days for 1-2 courses in the absence of
disease progression or unacceptable toxicity. Patients then proceed to transplant.

- First autologous PBSC transplantation: Beginning within 6 weeks to 3 months after
completion of induction therapy (or ≥ 1 week after completion of bridging therapy),
patients receive bortezomib IV on days -4 and -1 and melphalan IV, oral thalidomide,
and oral dexamethasone on days -4 to -1. Patients undergo autologous PBSC
transplantation on day 0.

- Inter-transplant bridging therapy: Patients with persistent disease after completion of
the first autologous PBSC transplant receive bridging therapy as above and then proceed
to the second transplant. Patients not requiring bridging therapy proceed directly to
the second transplant.

- Second autologous PBSC transplantation: Beginning within 6 months after the first PBSC
transplant, patients receive bortezomib, melphalan, thalidomide, and dexamethasone and
undergo autologous PBSC as in the first transplant. Patients who skip the second
transplant (due to medical or insurance reasons or refusal) proceed to consolidation
therapy.

- Consolidation therapy: Beginning within 6 months after the last transplant, patients
receive bortezomib, thalidomide, dexamethasone, cisplatin, doxorubicin hydrochloride,
cyclophosphamide, and etoposide as in induction therapy.

- Post-consolidation bridging therapy: Patients with persistent disease after completion
of consolidation therapy receive oral thalidomide on days 1-21 and oral dexamethasone
on days 1, 8, and 15. Patients then proceed to maintenance therapy. Patients not
requiring bridging therapy proceed directly to maintenance therapy.

- Maintenance therapy: Beginning within 4 months after completion of consolidation
therapy or post-consolidation bridging therapy, patients receive bortezomib IV and oral
dexamethasone on days 1, 8, 15, and 22 and oral lenalidomide on days 1-20. Courses
repeat every 28 days for up to 3 years in the absence of disease progression or
unacceptable toxicity.

Blood and bone marrow samples may be collected at baseline and periodically during study for
gene expression profile analysis.

After completion of study therapy, patients are followed up periodically for up to 7 years.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Newly diagnosed active multiple myeloma (MM)

- Measurable disease

- Non-secretory disease allowed provided patient has ≥ 20% plasmacytosis or
multiple (> 3) focal plasmacytomas on skeletal survey and/or MRI

PATIENT CHARACTERISTICS:

- Zubrod performance status (PS) 0-2 (Zubrod PS 3-4 allowed if based solely on bone
pain)

- ANC ≥ 1,500/mm^3*

- Platelet count ≥ 150,000/mm^3*

- Serum creatinine clearance of ≥ 60 mL/min

- Patients with creatinine clearance of < 60 mL/min receive a lower dose of
melphalan

- No patients receiving or planning to receive dialysis

- Total bilirubin ≤ 1.5 times upper limit of normal

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Must be fully aware of the teratogenic potential of thalidomide

- Must be willing to comply with the FDA-mandated S.T.E.P.S. program

- Ejection fraction > 40% as measured by MUGA scan or two-dimensional ECHO

- No peripheral neuropathy ≥ grade 2 per CTCAE v. 4.0

- No known hypersensitivity to bortezomib, boron, or mannitol

- No uncontrolled diabetes defined as fasting glucose level > 200 mg/dL on at least
more than two occasions or more that two serum random blood levels > 300 mg/dL
despite adequate treatment

- Patients with a history of diabetes mellitus requiring treatment should be on a
stable regimen and have their blood glucose closely monitored

- No other malignancy within the past 5 years 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 within the past year NOTE: *Unless myeloma-related
marrow infiltration is documented, defined as ≥ 30% marrow cellularity with 50% of
the cells being malignant plasma cells.

PRIOR CONCURRENT THERAPY:

- At least 4 weeks since prior chemotherapy or radiotherapy

- No more than 1 prior course of chemotherapy for MM

- Prior chemotherapy must not have included melphalan

- No prior radiotherapy to large area of the pelvis (more than half of the pelvis)

- Prior radiotherapy for symptomatic localized bone lesions or impending cord
compression allowed

Type of Study:

Interventional

Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival at 3 years

Outcome Time Frame:

3 years

Safety Issue:

No

Principal Investigator

Muneer H. Abidi, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Barbara Ann Karmanos Cancer Institute

Authority:

United States: Federal Government

Study ID:

CDR0000663952

NCT ID:

NCT01055301

Start Date:

July 2011

Completion Date:

July 2011

Related Keywords:

  • Multiple Myeloma
  • Plasma Cell Myeloma
  • stage I multiple myeloma
  • stage II multiple myeloma
  • stage III multiple myeloma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell

Name

Location

Fred Hutchinson Cancer Research CenterSeattle, Washington  98109
Barbara Ann Karmanos Cancer InstituteDetroit, Michigan  48201
Swedish Cancer Institute at Swedish Medical Center - First Hill CampusSeattle, Washington  98104
Olympic Hematology and OncologyBremerton, Washington  98310
Skagit Valley Hospital Cancer Care CenterMt. Vernon, Washington  98273
University Cancer Center at University of Washington Medical CenterSeattle, Washington  98195
Harborview Medical CenterSeattle, Washington  98104
Group Health Central HospitalSeattle, Washington  98104
North Puget Oncology at United General HospitalSedro-Wooley, Washington  98284
Cancer Care Northwest - Spokane SouthSpokane, Washington  99202
Tulane Cancer Center Office of Clinical ResearchAlexandria, Louisiana  71315-3198
University of Mississippi Cancer ClinicJackson, Mississippi  39216-4505
Minor and James Medical, PLLCSeattle, Washington  98104
St. Joseph Cancer CenterBellingham, Washington  98225
Columbia Basin HematologyKennewick, Washington  99336
Harrison Poulsbo Hematology and OnocologyPoulsbo, Washington  98370
Evergreen Hematology and Oncology, PSSpokane, Washington  99218
Wenatchee Valley Medical CenterWenatchee, Washington  98801-2028
Hematology-Oncology ClinicBaton Rouge, Louisiana  70808
Island Hospital Cancer Care Center at Island HospitalAnacortes, Washington  98221
Highline Medical Center Cancer CenterBurien, Washington  98166