UARK 2012-02 Trial For High-Risk Myeloma Evaluating Accelerating and Sustaining Complete Remission

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02128230
Recruitment Status : Recruiting
First Posted : May 1, 2014
Last Update Posted : October 16, 2018
Information provided by (Responsible Party):
University of Arkansas

April 29, 2014
May 1, 2014
October 16, 2018
August 2014
May 2025   (Final data collection date for primary outcome measure)
The remission rate for participants with high-risk myeloma [ Time Frame: 132 months ]
To determine the remission rate for participants with high-risk myeloma [ Time Frame: 132 months ]
Complete list of historical versions of study NCT02128230 on Archive Site
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UARK 2012-02 Trial For High-Risk Myeloma Evaluating Accelerating and Sustaining Complete Remission
A Phase II Trial For High-Risk Myeloma Evaluating Accelerating and Sustaining Complete Remission (AS-CR) by Applying Non-Host -Exhausting and Timely Dose-Reduced Mel-80-CFZ-TD-Pace Transplant(s) With Interspersed Mel-20-CFZ-TD-Pace With CFZ-RD and CFZ-D Maintenance
The purpose of this study is to improve the clinical outcomes of research subjects with high-risk multiple myeloma in the context of the immediately preceding Total therapy 5 trial 2008-02 and Total therapy 3 trials 2003-33 and 2006-66.

Total therapy 5B will attempt to accelerate and sustain, at 2 years from starting therapy, the proportion of subjects in complete remission by reducing host-imposed toxicity and facilitating timely completion of highly synergistic 8-drug combination therapy, including the next generation proteasome inhibitor, Carfilzomib. This will result in avoiding multiple myeloma re-growth that, we postulate, ensued in Total therapy 3 during recovery phases from severe de-conditioning. It is speculated that the incidence of positive minimal residual disease will be reduced with the addition of one cycle of consolidation therapy. The following approach will be implemented:

  • apply a 4-day fractionated lower dose melphalan (80 mg/m2) together with CFZ-TD-PACE regimen in MEL80-CFZ-TD (carfilzomib, thalidomide, dexamethasone) PACE as a hopefully less toxic and more effective transplant regimen
  • interspersed with 1 cycle of non-transplant supported MEL-20-CFZ-TD (carfilzomib, thalidomide, dexamethasone) PACE (in lower doses than with transplant) inter-therapy (reduced from two cycles due to prolonged thrombocytopenia)
  • followed by CFZ-TD (carfilzomib, thalidomide, dexamethasone) PACE consolidation therapy post transplant #2
  • CFZ-RD (carfilzomib, lenalidomide and dexamethasone) maintenance for 1 year followed by CFZ-D for an additional year
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Multiple Myeloma
Melphalan and Carfilzomib will be given into a central venous catheter. Dexamethasone is a pill that is taken by mouth daily for 4 days. Thalidomide is a capsule taken by mouth for 4 days. Cisplatin, Adriamycin, Cyclophosphamide and Etoposide are all given into the vein (IV) by a continuous infusion through a central catheter for 4 days. After completion of the four days of continuous chemotherapy, a drug G-CSF will be given. This is a shot just under the skin to help the bone marrow and blood counts recover more quickly after chemotherapy.
Other Names:
  • Melphalan
  • Carfilzomib-CFZ
  • Thalidomide
  • Dexamethasone
  • Cisplatin
  • Adriamycin
  • Cyclophosphamide
  • Etoposide
  • G-CSF
Experimental: Study Treatment
Intervention: Drug: MEL-CFZ-TD-PACE
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*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Same as current
May 2025
May 2025   (Final data collection date for primary outcome measure)

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 high-risk disease, as defined by GEP70 risk score of ≥ 0.66
  • Zubrod ≤ 2, unless solely due to symptoms of MM-related bone disease.
  • Patients must have a platelet count of ≥ 50,000/μL, unless lower levels are explained by extensive bone marrow plasmacytosis.
  • 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 scan ≥ 45%
  • 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:

  • Does not have high-risk disease
  • 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.
  • Patients must not have prior malignancy, 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 for one year prior to enrollment. Other cancers will only be acceptable if the patient's life expectancy exceeds five years.
  • Pregnant or nursing women may not participate. Women of childbearing potential must have a negative pregnancy documented within one week of registration. Subjects of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
Sexes Eligible for Study: All
18 Years to 75 Years   (Adult, Older Adult)
Contact: Nathan M Petty 501-526-6990 ext 2435
Contact: David Avery 501-526-6990 ext 2431
United States
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University of Arkansas
University of Arkansas
Principal Investigator: Frits Van Rhee, MD, Ph.D University of Arkansas
University of Arkansas
October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP