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NCT02128230 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase
PHASE2
Status at capture
TERMINATED
Registry last update
2021-06-22

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

The Remission Rate for Participants With High-risk Myeloma

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
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 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.
healthy Volunteers
false
maximum Age
75 Years
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    Induction, optional bridging, first transplant, optional bridging, inter-therapy, optional bridging, second transplant, optional bridging, consolidation, maintenance
    intervention Names
    1. Device: myPRS
    2. Drug: Induction 1 - MEL-10+CFZ-TD-PACE
    3. Drug: First Transplant - MEL-80+CFZ-TD-PACE + PBSC (biologic)
    4. Drug: Inter-Therapy - MEL-20+CFZ-TD-PACE (75%)
    5. Drug: Second Transplant - MEL-80+CFZ-TD-PACE + PBSC (biologic)
    6. Drug: Consolidation - CFZ-TD-PACE
    7. Drug: Maintenance - CFZ-R(T)-D
    label
    Total Therapy 5b
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Total Therapy 5b
    description
    Genome expression profiling used to identify high-risk and low-risk multiple myeloma
    name
    myPRS
    other Names
    1. Gep70
    type
    DEVICE
  2. arm Group Labels
    1. Total Therapy 5b
    description
    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.
    name
    Induction 1 - MEL-10+CFZ-TD-PACE
    other Names
    1. Melphalan (Alkeran™)
    2. Carfilzomib (Kyprolis®)
    3. Thalidomide (Thalomid®)
    4. Dexamethasone (Decadron®)
    5. Cisplatin (CDDP) (Platinol®)
    6. Doxorubicin (Adriamycin®)
    7. Cyclophosphamide (Cytoxan®)
    8. Etoposide (VP-16) (Vepesid®)
    9. Granulocyte colony-stimulating factor (G-CSF), filgrastim (Neupogen®)
    type
    DRUG
  3. arm Group Labels
    1. Total Therapy 5b
    description
    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.
    name
    First Transplant - MEL-80+CFZ-TD-PACE + PBSC (biologic)
    other Names
    1. Autologous Peripheral Blood Stem Cell Transplant
    2. Melphalan (Alkeran™)
    3. Carfilzomib (Kyprolis®)
    4. Thalidomide (Thalomid®)
    5. Dexamethasone (Decadron®)
    6. Cisplatin (CDDP) (Platinol®)
    7. Doxorubicin (Adriamycin®)
    8. Cyclophosphamide (Cytoxan®)
    9. Etoposide (VP-16) (Vepesid®)
    type
    DRUG
  4. arm Group Labels
    1. Total Therapy 5b
    description
    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.
    name
    Inter-Therapy - MEL-20+CFZ-TD-PACE (75%)
    other Names
    1. Melphalan (Alkeran™)
    2. Carfilzomib (Kyprolis®)
    3. Thalidomide (Thalomid®)
    4. Dexamethasone (Decadron®)
    5. Cisplatin (CDDP) (Platinol®)
    6. Doxorubicin (Adriamycin®)
    7. Cyclophosphamide (Cytoxan®)
    8. Etoposide (VP-16) (Vepesid®)
    type
    DRUG
  5. arm Group Labels
    1. Total Therapy 5b
    description
    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.
    name
    Second Transplant - MEL-80+CFZ-TD-PACE + PBSC (biologic)
    other Names
    1. Autologous Peripheral Blood Stem Cell Transplant
    2. Melphalan (Alkeran™)
    3. Carfilzomib (Kyprolis®)
    4. Thalidomide (Thalomid®)
    5. Dexamethasone (Decadron®)
    6. Cisplatin (CDDP) (Platinol®)
    7. Doxorubicin (Adriamycin®)
    8. Cyclophosphamide (Cytoxan®)
    9. Etoposide (VP-16) (Vepesid®)
    type
    DRUG
  6. arm Group Labels
    1. Total Therapy 5b
    description
    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.
    name
    Consolidation - CFZ-TD-PACE
    other Names
    1. Carfilzomib (Kyprolis®)
    2. Thalidomide (Thalomid®)
    3. Dexamethasone (Decadron®)
    4. Cisplatin (CDDP) (Platinol®)
    5. Doxorubicin (Adriamycin®)
    6. Cyclophosphamide (Cytoxan®)
    7. Etoposide (VP-16) (Vepesid®)
    type
    DRUG
  7. arm Group Labels
    1. Total Therapy 5b
    description
    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.
    name
    Maintenance - CFZ-R(T)-D
    other Names
    1. Carfilzomib (Kyprolis®)
    2. Lenalidomide (CC-5013) (Revlimid®)
    3. Dexamethasone (Decadron®)
    4. Thalidomide (Thalomid®)
    type
    DRUG
Study design
allocation
NA
intervention Model
SINGLE_GROUP
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
20
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    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.
    measure
    The Remission Rate for Participants With High-risk Myeloma
    time Frame
    from baseline to either death or study completion for each subject (up to approximately 48 months)
Full study description
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.
detailed Description
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
Source references
references
  1. citation
    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
    type
    DERIVED
  2. citation
    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
    type
    DERIVED
Source notices and limitations
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    Preserved source evidence · Not medical advice