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

NCT02128230 | Terminated Phase 2 Results DMC FDA Drug FDA Device

• 1 other identifier: 134668
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Multiple Myeloma

Keywords

High-Risk; Carfilzomib

Outcome Measures

Primary Outcomes (1)

• The Remission Rate for Participants With High-risk Myeloma

  Toward improving the clinical outcomes of research subjects with high-risk MM (HR-MM) in the context of the immediately preceding TT5 trial 2008-02 and TT3 trials 2003-33 and 2006-66, TT5B will attempt to accelerate and sustain, at 2 years from starting therapy, the proportion of subjects in complete remission (AS-CR-2) by reducing host-imposed toxicity and thus facilitating timely completion of highly synergistic 8-drug combination therapy, including the next generation proteasome inhibitor, Carfilzomib (CFZ). This will result in avoiding MM re-growth that, we postulate, ensued in TT3 during recovery phases from severe de-conditioning. Furthermore, we speculate that the incidence of positive minimal residual disease (MRD) will be reduced with the addition of one cycle of consolidation therapy.

  from baseline to either death or study completion for each subject (up to approximately 48 months)

Study Arms (1)

Total Therapy 5b

EXPERIMENTAL

Induction, optional bridging, first transplant, optional bridging, inter-therapy, optional bridging, second transplant, optional bridging, consolidation, maintenance

Device: myPRS; Drug: Induction 1 - MEL-10+CFZ-TD-PACE; Drug: First Transplant - MEL-80+CFZ-TD-PACE + PBSC (biologic); Drug: Inter-Therapy - MEL-20+CFZ-TD-PACE (75%); Drug: Second Transplant - MEL-80+CFZ-TD-PACE + PBSC (biologic); Drug: Consolidation - CFZ-TD-PACE; Drug: Maintenance - CFZ-R(T)-D

Interventions

myPRS DEVICE

Genome expression profiling used to identify high-risk and low-risk multiple myeloma

Also known as: Gep70

Total Therapy 5b

Induction 1 - MEL-10+CFZ-TD-PACE DRUG

Melphalan (MEL) and Carfilzomib (CFZ) will be given into a central venous catheter. Thalidomide (T) is a capsule and Dexamethasone (D) is a pill; both will be taken by mouth. Cisplatin (P), Adriamycin (A), Cyclophosphamide (C) and Etoposide (E) are all given into the vein (IV) by a continuous infusion through a central catheter. After completion of the continuous chemotherapy, Granulocyte colony-stimulating factor (G-CSF), a shot just under the skin to help the bone marrow and blood counts recover more quickly after chemotherapy, will be given. Regimen: CFZ 20 mg/m2 on days 1, 5, \& 6; MEL 10mg/m2 on day 3; T 200 mg/d, D 40 mg/d, P 10 mg/m2/d, A 10 mg/m2/d, C 400 mg/m2/d, and E 40 mg/m2/d on days 5-8; G-CSF 10 mcg/kg/day from day 11 through end of Peripheral Blood Stem Cell (PBSC) collection. Optional Bridging with T 50 mg/d and D 20 mg on day 1-4 every 21 days until 1st transplant.

Also known as: Melphalan (Alkeran™), Carfilzomib (Kyprolis®), Thalidomide (Thalomid®), Dexamethasone (Decadron®), Cisplatin (CDDP) (Platinol®), Doxorubicin (Adriamycin®), Cyclophosphamide (Cytoxan®), Etoposide (VP-16) (Vepesid®), Granulocyte colony-stimulating factor (G-CSF), filgrastim (Neupogen®)

Total Therapy 5b

First Transplant - MEL-80+CFZ-TD-PACE + PBSC (biologic) DRUG

Melphalan (MEL) and Carfilzomib (CFZ) will be given into a central venous catheter. Thalidomide (T) is a capsule and Dexamethasone (D) is a pill; both will be taken by mouth. Cisplatin (P), Adriamycin (A), Cyclophosphamide (C) and Etoposide (E) are all given into the vein (IV) by a continuous infusion through a central catheter. After completion of the continuous chemotherapy, Granulocyte colony-stimulating factor (G-CSF), a shot just under the skin to help the bone marrow and blood counts recover more quickly after chemotherapy, will be given. Regimen: CFZ 20 mg/m2 on days -5 \& -4; MEL 20 mg/m2/d, T 200 mg/d, D 40 mg/d, P 10 mg/m2/d, A 10 mg/m2/d, C 100 mg/m2/d, and E 80 mg/m2/d on days -5 \& -2; PBSC transplant on day 0. Optional Bridging with T 50 mg/d and D 20 mg on day 1-4 every 21 days until inter-therapy.

Also known as: Autologous Peripheral Blood Stem Cell Transplant, Melphalan (Alkeran™), Carfilzomib (Kyprolis®), Thalidomide (Thalomid®), Dexamethasone (Decadron®), Cisplatin (CDDP) (Platinol®), Doxorubicin (Adriamycin®), Cyclophosphamide (Cytoxan®), Etoposide (VP-16) (Vepesid®)

Total Therapy 5b

Inter-Therapy - MEL-20+CFZ-TD-PACE (75%) DRUG

Melphalan (MEL) and Carfilzomib (CFZ) will be given into a central venous catheter. Thalidomide (T) is a capsule and Dexamethasone (D) is a pill; both will be taken by mouth. Cisplatin (P), Adriamycin (A), Cyclophosphamide (C) and Etoposide (E) are all given into the vein (IV) by a continuous infusion through a central catheter. After completion of the continuous chemotherapy, Granulocyte colony-stimulating factor (G-CSF), a shot just under the skin to help the bone marrow and blood counts recover more quickly after chemotherapy, will be given. Regimen: CFZ 27 mg/m2 on days 1-2; MEL 5 mg/m2/d, T 200 mg/d, D 20 mg/d, P 7.5 mg/m2/d, A 7.5 mg/m2/d, C 75 mg/m2/d, and E 60 mg/m2/d on days 1-4. Optional Bridging with T 50 mg/d and D 20 mg on day 1-4 every 21 days until 2nd transplant.

Also known as: Melphalan (Alkeran™), Carfilzomib (Kyprolis®), Thalidomide (Thalomid®), Dexamethasone (Decadron®), Cisplatin (CDDP) (Platinol®), Doxorubicin (Adriamycin®), Cyclophosphamide (Cytoxan®), Etoposide (VP-16) (Vepesid®)

Total Therapy 5b

Second Transplant - MEL-80+CFZ-TD-PACE + PBSC (biologic) DRUG

Melphalan (MEL) and Carfilzomib (CFZ) will be given into a central venous catheter. Thalidomide (T) is a capsule and Dexamethasone (D) is a pill; both will be taken by mouth. Cisplatin (P), Adriamycin (A), Cyclophosphamide (C) and Etoposide (E) are all given into the vein (IV) by a continuous infusion through a central catheter. After completion of the continuous chemotherapy, Granulocyte colony-stimulating factor (G-CSF), a shot just under the skin to help the bone marrow and blood counts recover more quickly after chemotherapy, will be given. Regimen: CFZ 20 mg/m2 on days -5 \& -4; MEL 20 mg/m2/d, T 200 mg/d, D 40 mg/d, P 10 mg/m2/d, A 10 mg/m2/d, C 100 mg/m2/d, and E 80 mg/m2/d on days -5 \& -2; PBSC transplant on day 0. Optional Bridging with T 50mg/d and D 20 mg on day 1-4 every 21 days until consolidation.

Also known as: Autologous Peripheral Blood Stem Cell Transplant, Melphalan (Alkeran™), Carfilzomib (Kyprolis®), Thalidomide (Thalomid®), Dexamethasone (Decadron®), Cisplatin (CDDP) (Platinol®), Doxorubicin (Adriamycin®), Cyclophosphamide (Cytoxan®), Etoposide (VP-16) (Vepesid®)

Total Therapy 5b

Consolidation - CFZ-TD-PACE DRUG

Carfilzomib (CFZ) will be given into a central venous catheter. Thalidomide (T) is a capsule and dexamethasone (D) is a pill; both will be taken by mouth. Cisplatin (P), adriamycin (A), cyclophosphamide (C) and etoposide (E) are all given into the vein (IV) by a continuous infusion through a central catheter. Regimen: CFZ 27 mg/m2 on days 1-2; T 200 mg/d, D 40 mg/d, P 7.5 mg/m2/d, A 7.5 mg/m2/d, C 300 mg/m2/d, and E 30 mg/m2/d on days 1-4.

Also known as: Carfilzomib (Kyprolis®), Thalidomide (Thalomid®), Dexamethasone (Decadron®), Cisplatin (CDDP) (Platinol®), Doxorubicin (Adriamycin®), Cyclophosphamide (Cytoxan®), Etoposide (VP-16) (Vepesid®)

Total Therapy 5b

Maintenance - CFZ-R(T)-D DRUG

Carfilzomib (CFZ) will be given into a central venous catheter. Thalidomide (T) and lenalidomide (R) are capsules and dexamethasone (D) is a pill; all will be taken by mouth. Regimen: For Cycles 1-12 CFZ 27 mg/m2/wk and D 12 mg/wk on days 1, 8, 15, \& 22; lenalidomide (R) 15 mg/d on days 1-21. For Cycles 13-24 CFZ 27 mg/m2/wk and D 12 mg/wk on days 1, 8, 15, \& 22. T may be substituted for R at 100 mg/day at the treating physician's discretion.

Also known as: Carfilzomib (Kyprolis®), Lenalidomide (CC-5013) (Revlimid®), Dexamethasone (Decadron®), Thalidomide (Thalomid®)

Total Therapy 5b

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Arkansas: lead
• Amgen: collaborator

Study Sites (1)

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Related Publications (2)

• Pawlyn C. High-risk myeloma: a challenge to define and to determine the optimal treatment. Lancet Haematol. 2021 Jan;8(1):e4-e6. doi: 10.1016/S2352-3026(20)30361-6. Epub 2020 Dec 22. No abstract available.

  PMID: 33357481 DERIVED

• Davies 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.

  PMID: 29567784 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Melphalan; carfilzomib; Thalidomide; Dexamethasone; Calcium Dobesilate; Cisplatin; Doxorubicin; Cyclophosphamide; Etoposide; Granulocyte Colony-Stimulating Factor; Filgrastim; Biological Products; Lenalidomide

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Phosphoramides; Organophosphorus Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Proteins; Biological Factors; Complex Mixtures

Limitations and Caveats

The study was terminated early due to futility as determined by Amgen's Carfilzomib NASCR program in addition to low enrollment.

Results Point of Contact

• Title: Frits Van Rhee, MD
• Organization: University of Arkansas for Medical Sciences

vanrheefrits@uams.edu

501-526-2873

Study Officials

• Frits Van Rhee, MD, Ph.D

  University of Arkansas

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2014
• First Posted: May 1, 2014
• Study Start: June 10, 2014
• Primary Completion: February 19, 2019
• Study Completion: February 19, 2019
• Last Updated: June 22, 2021
• Results First Posted: June 22, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)