S1304, Carfilzomib and Dexamethasone for Treating Patients With Relapsed or Refractory Myeloma

Sponsor
Southwest Oncology Group (Other)
Overall Status
Completed
CT.gov ID
NCT01903811
Collaborator
National Cancer Institute (NCI) (NIH)
143
485
2
65.1
0.3
0

Study Details

Study Description

Brief Summary

This randomized phase II trial compares how well two different doses of carfilzomib work when given with dexamethasone in treating patients with multiple myeloma that has come back after a period of improvement or has not responded to treatment. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving carfilzomib together with dexamethasone may kill more cancer cells. It is not yet known whether a higher or lower dose of carfilzomib works better when given with dexamethasone.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

PRIMARY OBJECTIVES:
  1. To evaluate and compare progression free survival (PFS) of two different doses of carfilzomib with dexamethasone in multiple myeloma (MM) patients with relapsed and/or refractory disease.
SECONDARY OBJECTIVES:
  1. To evaluate and compare response rates (RR) for each arm. II. To evaluate response rates (RR) for patients that relapse on low dose carfilzomib and subsequently cross-over to high dose carfilzomib.

  2. To evaluate the safety of this combination for this patient population. IV. To evaluate overall survival (OS).

TERTIARY OBJECTIVES:
  1. To explore the molecular variability in MM cells obtained from extramedullary bone marrow relapse sites.

  2. To explore the role of positron emission tomography (PET) scanning in assessing disease burden and as a tool to assess treatment response.

  3. To explore changes in left ventricular ejection fraction (LVEF) in patients with relapsed or refractory multiple myeloma treated with low dose carfilzomib or high dose carfilzomib plus dexamethasone.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive dexamethasone intravenously (IV) and low-dose carfilzomib IV over 2-10 minutes on days 1, 2, 8, 9, 15, and 16. Patients with progression cross-over to Arm II.

ARM II: Patients receive dexamethasone IV and high-dose carfilzomib IV over 30 minutes on days 1, 2, 8, 9, 15, and 16.

Note that for the first course of treatment on both arms carfilzomib is given at a reduced rate to assess toxicity.

In both arms, treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 3 years from initial registration.

Study Design

Study Type:
Interventional
Actual Enrollment :
143 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Randomized Study Comparing Two Doses of Carfilzomib (NSC-756640) With Dexamethasone for Multiple Myeloma Patients With Relapsed or Refractory Disease
Study Start Date :
Oct 1, 2013
Actual Primary Completion Date :
Nov 1, 2017
Actual Study Completion Date :
Mar 7, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm I (dexamethasone, low-dose carfilzomib)

Patients receive dexamethasone IV and low-dose carfilzomib IV over 2-10 minutes on days 1, 2, 8, 9, 15, and 16. (Note that course 1 is given at a reduced dose.) Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients with progression cross-over to Arm II.

Drug: Carfilzomib
Given IV
Other Names:
  • Kyprolis
  • PR-171
  • Drug: Dexamethasone
    Given IV
    Other Names:
  • Aacidexam
  • Adexone
  • Aknichthol Dexa
  • Alba-Dex
  • Alin
  • Alin Depot
  • Alin Oftalmico
  • Amplidermis
  • Anemul mono
  • Auricularum
  • Auxiloson
  • Baycuten
  • Baycuten N
  • Cortidexason
  • Cortisumman
  • Decacort
  • Decadrol
  • Decadron
  • Decalix
  • Decameth
  • Decasone R.p.
  • Dectancyl
  • Dekacort
  • Deltafluorene
  • Deronil
  • Desamethasone
  • Desameton
  • Dexa-Mamallet
  • Dexa-Rhinosan
  • Dexa-Scheroson
  • Dexa-sine
  • Dexacortal
  • Dexacortin
  • Dexafarma
  • Dexafluorene
  • Dexalocal
  • Dexamecortin
  • Dexameth
  • Dexamethasonum
  • Dexamonozon
  • Dexapos
  • Dexinoral
  • Dexone
  • Dinormon
  • Fluorodelta
  • Fortecortin
  • Gammacorten
  • Hexadecadrol
  • Hexadrol
  • Lokalison-F
  • Loverine
  • Methylfluorprednisolone
  • Millicorten
  • Mymethasone
  • Orgadrone
  • Spersadex
  • Visumetazone
  • Other: Laboratory Biomarker Analysis
    Correlative studies

    Experimental: Arm II (dexamethasone, high-dose carfilzomib)

    Patients receive dexamethasone IV and high-dose carfilzomib IV over 30 minutes on days 1, 2, 8, 9, 15, and 16. (Note that course 1 is given at a reduced dose over 2-10 minutes.) Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

    Drug: Carfilzomib
    Given IV
    Other Names:
  • Kyprolis
  • PR-171
  • Drug: Dexamethasone
    Given IV
    Other Names:
  • Aacidexam
  • Adexone
  • Aknichthol Dexa
  • Alba-Dex
  • Alin
  • Alin Depot
  • Alin Oftalmico
  • Amplidermis
  • Anemul mono
  • Auricularum
  • Auxiloson
  • Baycuten
  • Baycuten N
  • Cortidexason
  • Cortisumman
  • Decacort
  • Decadrol
  • Decadron
  • Decalix
  • Decameth
  • Decasone R.p.
  • Dectancyl
  • Dekacort
  • Deltafluorene
  • Deronil
  • Desamethasone
  • Desameton
  • Dexa-Mamallet
  • Dexa-Rhinosan
  • Dexa-Scheroson
  • Dexa-sine
  • Dexacortal
  • Dexacortin
  • Dexafarma
  • Dexafluorene
  • Dexalocal
  • Dexamecortin
  • Dexameth
  • Dexamethasonum
  • Dexamonozon
  • Dexapos
  • Dexinoral
  • Dexone
  • Dinormon
  • Fluorodelta
  • Fortecortin
  • Gammacorten
  • Hexadecadrol
  • Hexadrol
  • Lokalison-F
  • Loverine
  • Methylfluorprednisolone
  • Millicorten
  • Mymethasone
  • Orgadrone
  • Spersadex
  • Visumetazone
  • Other: Laboratory Biomarker Analysis
    Correlative studies

    Outcome Measures

    Primary Outcome Measures

    1. Progression-free Survival [From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 2 years]

      Assessed in each arm using the method of Kaplan Meier and compared between arms using the stratified long-rank test. Progression is defined using the International Uniform Response Criteria for Multiple Myeloma as new or increase in size of existing bone lesions or soft tissue plasmacytomas; or development of hypercalcemia attributable solely to MM; or ≥ 25% increase from baseline or lowest response level of either serum M protein, urine M protein, difference in involved & uninvolved serum free light chain level or bone marrow plasma cell percentage.

    Secondary Outcome Measures

    1. Overall Survival [From date of registration to date of death due to any cause, assessed up to 3 years]

      Assessed in each arm using the method of Kaplan Meier and compared between arms using the stratified log-rank test.

    2. Best Overall Response - Partial Response (PR), Very Good Partial Response (VGPR), Unconfirmed PR (uPR), Stable Disease (SD) Progression (PROG) [From date of registration to date of best response while on study treatment]

      Per International Uniform Response Criteria for Multiple Myeloma PR- ≥ 50% reduction in size of soft tissue plasmacytomas & plasma cells; ≥ 50% decrease in serum & reduction in urine M protein ≥ 90% or to < 200 mg/24hr or ≥ 50% decrease in difference in uninvolved & involved serum free light chain levels; VGPR- PR + Serum and urine M proteins detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M protein & urine M protein < 100 mg/24 hrs; uPR- 1 objective status of PR, but confirmation studies are not done, or do not meet the requirements necessary to confirm response; SD- does not meet criteria for sCR, CR, VGPR, PR or PROG; PROG- new or increase in size of existing bone lesions or soft tissue plasmacytomas/ development of hypercalcemia attributable solely to MM/ ≥ 25% increase from baseline/ lowest response level of either serum or Urine M protein, difference in involved & uninvolved serum free light chain level or bone marrow plasma cell percentage.

    3. Progression-free Survival of Crossover Group [From date of crossover to date of subsequent documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 3 years from randomization]

      Assessed in the crossover arm using the method of Kaplan Meier. Progression is defined using the International Uniform Response Criteria for Multiple Myeloma as new or increase in size of existing bone lesions or soft tissue plasmacytomas; or development of hypercalcemia attributable solely to MM; or ≥ 25% increase from baseline or lowest response level of either serum M protein, urine M protein, difference in involved & uninvolved serum free light chain level or bone marrow plasma cell percentage.

    4. Overall Survival Crossover Group [From date of crossover to date of death due to any cause, assessed up to 3 years from randomization]

      Assessed in the crossover arm using the method of Kaplan Meier.

    Other Outcome Measures

    1. Gene Expression Profiles [Up to 3 years]

      Bone marrow compared to that of an aspirate taken at the site of the EMP. Data will be log-transformed before analysis. Exploratory analyses will examine underlying distributions using boxplots, density plots, scatter plots, etc. For differential expression analysis of the two sample types t-tests will be conducted on genes. False discovery rate will be used to control the average false positive proportions among selected genes. Genes will be ranked by their q-value and pathway analysis conducted upon selected genes to determine biological plausibility and relevance to molecular functionality.

    2. Incidence of CR by PET, Defined as the Disappearance of All Focal Lesions and the Resolution of EMD [Up to week 45]

      Univariate and multivariate logistic regression will be used to determine the impact of biochemical CR on CR by PET. In the multivariate analysis adjustment for standard prognostic factors such as age, albumin, beta-2 microglobulin, serum creatinine, c-reactive protein and lactate dehydrogenase will be included.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • REGISTRATION STEP 1: INITIAL RANDOMIZATION

    • Patients must have a confirmed diagnosis of symptomatic multiple myeloma and must be currently relapsed or refractory; all tests for establishing disease status must be completed within 28 days prior to registration and documented on the Baseline Tumor Assessment Form for Multiple Myeloma

    • Patients must have measurable disease within 28 days prior to registration

    • Patients must have received at least one prior regimen of chemotherapy for symptomatic multiple myeloma; patients may not have more than six (6) previous regimens of therapy for the disease; prior chemotherapy must have been completed at least 21 days prior to registration; for study purposes, a regimen is defined as follows:

    • An anti-myeloma therapy used at the time of initial diagnosis or documented disease progression which is given with the intent to decrease disease burden

    • Any maintenance therapy used after an Induction should be considered part of that Induction regimen

    • Use of any agent or combination of agents more than once during the patient's disease history for separate documented disease progressions will be counted as separate regimens (e.g., if a patient receives lenalidomide/bortezomib at initial diagnosis and achieves response, but then progresses and receives lenalidomide/bortezomib after progression, these count as 2 separate regimens)

    • In cases of allogeneic or autologous stem cell transplant, the entire induction + stem cell mobilization + conditioning + planned maintenance should be considered one regimen

    • Patients may not have received any prior carfilzomib treatment

    • Patients must not be receiving any other concurrent therapy considered to be investigational; patients must not be planning to receive any radiotherapy (except localized radiation for palliative care); patients must not be planning to receive any concurrent chemotherapy, immunotherapy, radiotherapy or other treatment with curative intent

    • Patients must have complete history and physical examination within 28 days prior to registration

    • Patients must have baseline PET scan within 28 days prior to registration; note that images are submitted centrally for review

    • Patients with non-secretory MM or known primary amyloidosis are not eligible

    • Patients must have Zubrod performance status 0-2

    • Patients must not have clinically significant illness including uncontrolled, active infection requiring intravenous antibiotics, New York Heart Association (NYHA) class III or class IV heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, or >= grade 3 cardiac arrhythmias

    • Patients must have undergone an electrocardiogram (EKG) within 28 days prior to registration

    • Patients must have either echocardiogram (ECHO) with ejection fraction >= 45% within 28 days prior to registration

    • Patients must not have > grade 2 neuropathy and/or POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)

    • Total bilirubin =< 1.5 x upper limit of normal (ULN)

    • Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) =< 3 x ULN

    • Absolute neutrophil count (ANC) >= 1,000 cell/mm^3 without growth factor support within 14 days prior to registration

    • Platelets >= 50,000 cells/mm3 for patients who have bone marrow plasmacytosis < 50% or >= 30,000 cells/mm3 for patients who have bone marrow plasmacytosis of >= 50% within 14 days prior to registration

    • Calculated or measured creatinine clearance >= 30 ml/min within 14 days prior to registration

    • Patients who are known to be human immunodeficiency virus positive (HIV+) are eligible providing they meet all of the following additional criteria within 28 days prior to registration:

    • Cluster of differentiation (CD)4 cells >= 500/mm^3

    • Viral load of < 50 copies HIV messenger ribonucleic acid (mRNA)/mm^3 if on combination antiretroviral therapy (cART) or < 25,000 copies HIV mRNA if not on cART

    • No zidovudine or stavudine as part of cART

    • Patients who are HIV+ and do not meet all of these criteria are not eligible for this study

    • Patients with known hepatitis B or hepatitis C infection must have viral load < 800,000 IU/L within 28 days prior to registration

    • Patients must have baseline skeletal survey to document lytic lesions, osteopenia or compression fracture within 28 days prior to registration

    • Patients may have received palliative external beam radiation therapy (XRT) for local disease control with no curative intent. XRT must be completed at least 7 days prior to registration

    • Patients must be offered participation in specimen submission for translational medicine studies and banking; with patient consent, specimens must be submitted

    • Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures

    • No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for three years

    • Patients or their legally authorized representative must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines

    • As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

    • REGISTRATION STEP 2: CROSSOVER

    • Patient must have been eligible for and initially randomized to Arm 1 (low dose carfilzomib), begun cycle 2 of treatment, and progressed prior to completing 12 cycles of protocol therapy

    • At least 14 days and no more than 28 days must have elapsed between the last day of treatment on Arm 1 and registration to Arm 3

    • Patients must have recovered from all non-hematologic toxicities to =< grade 2 and from all hematologic toxicities to =< grade 3 prior to registration

    • Patients must have begun cycle 2 (carfilzomib - 27 mg/m^2) and must not have received any dose reduction for toxicity in the last cycle of treatment, immediately preceding progression

    • Patients must have serum protein electrophoresis (SPEP) and kappa and lambda light chain testing performed within 14 days prior to registration in order to establish baseline measurements

    • Patients must not have ejection fraction decrease > 10% from baseline (as determined by ECHO) or other ejection fraction decrease accompanied by other clinical signs/symptoms of New York Heart Association (NYHA) class III or IV heart failure, measured within 28 days prior to registration; if any question exists regarding individual patient eligibility in this situation, contact the study chair for determination

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Fairbanks Memorial Hospital Fairbanks Alaska United States 99701
    2 University of Arizona Cancer Center-North Campus Tucson Arizona United States 85719
    3 The University of Arizona Medical Center-University Campus Tucson Arizona United States 85724
    4 Kaiser Permanente-Anaheim Anaheim California United States 92807
    5 Kaiser Permanente-Deer Valley Medical Center Antioch California United States 94531
    6 Sutter Auburn Faith Hospital Auburn California United States 95602
    7 Sutter Cancer Centers Radiation Oncology Services-Auburn Auburn California United States 95603
    8 Kaiser Permanente-Baldwin Park Baldwin Park California United States 91706
    9 Kaiser Permanente-Bellflower Bellflower California United States 90706
    10 Alta Bates Summit Medical Center-Herrick Campus Berkeley California United States 94704
    11 Mills - Peninsula Hospitals Burlingame California United States 94010
    12 Sutter Cancer Centers Radiation Oncology Services-Cameron Park Cameron Park California United States 95682
    13 Eden Hospital Medical Center Castro Valley California United States 94546
    14 John Muir Medical Center-Concord Campus Concord California United States 94520
    15 Sutter Davis Hospital Davis California United States 95616
    16 Kaiser Permanente Hospital Fontana California United States 92335
    17 Kaiser Permanente-Fremont Fremont California United States 94538
    18 Kaiser Permanente Fresno California United States 93720
    19 Kaiser Permanente - Harbor City Harbor City California United States 90710
    20 Kaiser Permanente-Irvine Irvine California United States 92618
    21 Kaiser Permanente Los Angeles Medical Center Los Angeles California United States 90027
    22 Los Angeles County-USC Medical Center Los Angeles California United States 90033
    23 USC / Norris Comprehensive Cancer Center Los Angeles California United States 90033
    24 Kaiser Permanente-Cadillac Los Angeles California United States 90034
    25 Fremont - Rideout Cancer Center Marysville California United States 95901
    26 Memorial Medical Center Modesto California United States 95355
    27 Kaiser Permanente-Modesto Modesto California United States 95356
    28 Palo Alto Medical Foundation-Camino Division Mountain View California United States 94040
    29 Palo Alto Medical Foundation-Gynecologic Oncology Mountain View California United States 94040
    30 USC Norris Oncology/Hematology-Newport Beach Newport Beach California United States 92663
    31 Sutter Cancer Research Consortium Novato California United States 94945
    32 Kaiser Permanente-Oakland Oakland California United States 94611
    33 UC Irvine Health/Chao Family Comprehensive Cancer Center Orange California United States 92868
    34 Palo Alto Medical Foundation Health Care Palo Alto California United States 94301
    35 Kaiser Permanente - Panorama City Panorama City California United States 91402
    36 Kaiser Permanente-Redwood City Redwood City California United States 94063
    37 Kaiser Permanente-Richmond Richmond California United States 94801
    38 Kaiser Permanente-Riverside Riverside California United States 92505
    39 Kaiser Permanente-Roseville Roseville California United States 95661
    40 Sutter Cancer Centers Radiation Oncology Services-Roseville Roseville California United States 95661
    41 Sutter Roseville Medical Center Roseville California United States 95661
    42 Sutter General Hospital Sacramento California United States 95816
    43 University of California Davis Comprehensive Cancer Center Sacramento California United States 95817
    44 Kaiser Permanente-South Sacramento Sacramento California United States 95823
    45 Kaiser Permanente - Sacramento Sacramento California United States 95825
    46 Kaiser Permanente-San Diego Mission San Diego California United States 92108
    47 Kaiser Permanente-San Diego Zion San Diego California United States 92120
    48 California Pacific Medical Center-Pacific Campus San Francisco California United States 94115
    49 Kaiser Permanente-San Francisco San Francisco California United States 94115
    50 Kaiser Permanente-Santa Teresa-San Jose San Jose California United States 95119
    51 Kaiser Permanente San Leandro San Leandro California United States 94577
    52 Kaiser Permanente-San Marcos San Marcos California United States 92069
    53 Kaiser Permanente-San Rafael San Rafael California United States 94903
    54 Kaiser Permanente Medical Center - Santa Clara Santa Clara California United States 95051
    55 Palo Alto Medical Foundation-Santa Cruz Santa Cruz California United States 95065
    56 Kaiser Permanente-Santa Rosa Santa Rosa California United States 95403
    57 Sutter Pacific Medical Foundation Santa Rosa California United States 95403
    58 Kaiser Permanente-South San Francisco South San Francisco California United States 94080
    59 Kaiser Permanente-Stockton Stockton California United States 95210
    60 Palo Alto Medical Foundation-Sunnyvale Sunnyvale California United States 94086
    61 Gene Upshaw Memorial Tahoe Forest Cancer Center Truckee California United States 96161
    62 Sutter Cancer Centers Radiation Oncology Services-Vacaville Vacaville California United States 95687
    63 Kaiser Permanente Medical Center-Vacaville Vacaville California United States 95688
    64 Kaiser Permanente-Vallejo Vallejo California United States 94589
    65 Sutter Solano Medical Center/Cancer Center Vallejo California United States 94589
    66 Kaiser Permanente-Walnut Creek Walnut Creek California United States 94596
    67 John Muir Medical Center-Walnut Creek Walnut Creek California United States 94598
    68 Kaiser Permanente Woodland Hills California United States 91367
    69 Smilow Cancer Hospital-Derby Care Center Derby Connecticut United States 06418
    70 Smilow Cancer Hospital Care Center-Fairfield Fairfield Connecticut United States 06824
    71 Medical Oncology and Hematology Group PC-Guilford Guilford Connecticut United States 06437
    72 Smilow Cancer Hospital Care Center at Saint Francis Hartford Connecticut United States 06105
    73 Yale University New Haven Connecticut United States 06520
    74 Yale-New Haven Hospital North Haven Medical Center North Haven Connecticut United States 06473
    75 Smilow Cancer Hospital-Orange Care Center Orange Connecticut United States 06477
    76 Charlotte Hungerford Hospital Center for Cancer Care Torrington Connecticut United States 06790
    77 Smilow Cancer Hospital Care Center-Trumbull Trumbull Connecticut United States 06611
    78 Smilow Cancer Hospital-Waterbury Care Center Waterbury Connecticut United States 06708
    79 Beebe Medical Center Lewes Delaware United States 19958
    80 Christiana Gynecologic Oncology LLC Newark Delaware United States 19713
    81 Delaware Clinical and Laboratory Physicians PA Newark Delaware United States 19713
    82 Helen F Graham Cancer Center Newark Delaware United States 19713
    83 Medical Oncology Hematology Consultants PA Newark Delaware United States 19713
    84 Regional Hematology and Oncology PA Newark Delaware United States 19713
    85 Christiana Care Health System-Christiana Hospital Newark Delaware United States 19718
    86 Beebe Health Campus Rehoboth Beach Delaware United States 19971
    87 Nanticoke Memorial Hospital Seaford Delaware United States 19973
    88 Christiana Care Health System-Wilmington Hospital Wilmington Delaware United States 19801
    89 MedStar Georgetown University Hospital Washington District of Columbia United States 20007
    90 MedStar Washington Hospital Center Washington District of Columbia United States 20010
    91 University of Florida Gainesville Florida United States 32610
    92 Mayo Clinic in Florida Jacksonville Florida United States 32224-9980
    93 Florida Hospital Orlando Orlando Florida United States 32803
    94 Lewis Cancer and Research Pavilion at Saint Joseph's/Candler Savannah Georgia United States 31405
    95 Hawaii Oncology Inc-Pali Momi 'Aiea Hawaii United States 96701
    96 Pali Momi Medical Center 'Aiea Hawaii United States 96701
    97 Hawaii Cancer Care Inc-POB II Honolulu Hawaii United States 96813
    98 Queen's Medical Center Honolulu Hawaii United States 96813
    99 Straub Clinic and Hospital Honolulu Hawaii United States 96813
    100 University of Hawaii Cancer Center Honolulu Hawaii United States 96813
    101 Hawaii Cancer Care Inc-Liliha Honolulu Hawaii United States 96817
    102 Hawaii Oncology Inc-Kuakini Honolulu Hawaii United States 96817
    103 Kuakini Medical Center Honolulu Hawaii United States 96817
    104 Kaiser Permanente Moanalua Medical Center Honolulu Hawaii United States 96819
    105 Castle Medical Center Kailua Hawaii United States 96734
    106 Wilcox Memorial Hospital and Kauai Medical Clinic Lihue Hawaii United States 96766
    107 Saint Alphonsus Cancer Care Center-Boise Boise Idaho United States 83706
    108 Kootenai Medical Center Coeur d'Alene Idaho United States 83814
    109 Kootenai Cancer Center Post Falls Idaho United States 83854
    110 Kootenai Cancer Clinic Sandpoint Idaho United States 83864
    111 Rush - Copley Medical Center Aurora Illinois United States 60504
    112 Saint Joseph Medical Center Bloomington Illinois United States 61701
    113 Illinois CancerCare-Bloomington Bloomington Illinois United States 61704
    114 Illinois CancerCare-Canton Canton Illinois United States 61520
    115 Memorial Hospital of Carbondale Carbondale Illinois United States 62902
    116 Illinois CancerCare-Carthage Carthage Illinois United States 62321
    117 Centralia Oncology Clinic Centralia Illinois United States 62801
    118 Carle on Vermilion Danville Illinois United States 61832
    119 Cancer Care Center of Decatur Decatur Illinois United States 62526
    120 Decatur Memorial Hospital Decatur Illinois United States 62526
    121 Carle Physician Group-Effingham Effingham Illinois United States 62401
    122 Crossroads Cancer Center Effingham Illinois United States 62401
    123 Illinois CancerCare-Eureka Eureka Illinois United States 61530
    124 Illinois CancerCare-Galesburg Galesburg Illinois United States 61401
    125 Western Illinois Cancer Treatment Center Galesburg Illinois United States 61401
    126 Hinsdale Hematology Oncology Associates Incorporated Hinsdale Illinois United States 60521
    127 Illinois CancerCare-Kewanee Clinic Kewanee Illinois United States 61443
    128 Illinois CancerCare-Macomb Macomb Illinois United States 61455
    129 Carle Physician Group-Mattoon/Charleston Mattoon Illinois United States 61938
    130 Loyola University Medical Center Maywood Illinois United States 60153
    131 Garneau, Stewart C MD (UIA Investigator) Moline Illinois United States 61265
    132 Porubcin, Michael MD (UIA Investigator) Moline Illinois United States 61265
    133 Spector, David MD (UIA Investigator) Moline Illinois United States 61265
    134 Trinity Medical Center Moline Illinois United States 61265
    135 Illinois CancerCare-Monmouth Monmouth Illinois United States 61462
    136 Good Samaritan Regional Health Center Mount Vernon Illinois United States 62864
    137 Community Cancer Center Foundation Normal Illinois United States 61761
    138 Illinois CancerCare-Ottawa Clinic Ottawa Illinois United States 61350
    139 Radiation Oncology of Northern Illinois Ottawa Illinois United States 61350
    140 Illinois CancerCare-Pekin Pekin Illinois United States 61554
    141 OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center Pekin Illinois United States 61554
    142 Methodist Medical Center of Illinois Peoria Illinois United States 61603
    143 Illinois CancerCare-Peoria Peoria Illinois United States 61615
    144 OSF Saint Francis Radiation Oncology at Peoria Cancer Center Peoria Illinois United States 61615
    145 OSF Saint Francis Medical Center Peoria Illinois United States 61637
    146 Illinois CancerCare-Peru Peru Illinois United States 61354
    147 Valley Radiation Oncology Peru Illinois United States 61354
    148 Illinois CancerCare-Princeton Princeton Illinois United States 61356
    149 SwedishAmerican Regional Cancer Center/ACT Rockford Illinois United States 61114
    150 Central Illinois Hematology Oncology Center Springfield Illinois United States 62702
    151 Southern Illinois University School of Medicine Springfield Illinois United States 62702
    152 Springfield Clinic Springfield Illinois United States 62702
    153 Memorial Medical Center Springfield Illinois United States 62781
    154 Cancer Care Specialists of Illinois-Swansea Swansea Illinois United States 62226
    155 Carle Cancer Center Urbana Illinois United States 61801
    156 The Carle Foundation Hospital Urbana Illinois United States 61801
    157 Rush-Copley Healthcare Center Yorkville Illinois United States 60560
    158 Franciscan Saint Anthony Health-Michigan City Michigan City Indiana United States 46360
    159 Woodland Cancer Care Center Michigan City Indiana United States 46360
    160 Reid Health Richmond Indiana United States 47374
    161 Mary Greeley Medical Center Ames Iowa United States 50010
    162 McFarland Clinic PC-William R Bliss Cancer Center Ames Iowa United States 50010
    163 Constantinou, Costas L MD (UIA Investigator) Bettendorf Iowa United States 52722
    164 Hematology Oncology Associates-Quad Cities Bettendorf Iowa United States 52722
    165 McFarland Clinic PC-Boone Boone Iowa United States 50036
    166 Medical Oncology and Hematology Associates-West Des Moines Clive Iowa United States 50325
    167 Mercy Cancer Center-West Lakes Clive Iowa United States 50325
    168 Genesis Medical Center - East Campus Davenport Iowa United States 52803
    169 Iowa Methodist Medical Center Des Moines Iowa United States 50309
    170 Iowa-Wide Oncology Research Coalition NCORP Des Moines Iowa United States 50309
    171 Medical Oncology and Hematology Associates-Des Moines Des Moines Iowa United States 50309
    172 Medical Oncology and Hematology Associates-Laurel Des Moines Iowa United States 50314
    173 Mercy Medical Center - Des Moines Des Moines Iowa United States 50314
    174 Iowa Lutheran Hospital Des Moines Iowa United States 50316
    175 McFarland Clinic PC-Trinity Cancer Center Fort Dodge Iowa United States 50501
    176 McFarland Clinic PC-Jefferson Jefferson Iowa United States 50129
    177 McFarland Clinic PC-Marshalltown Marshalltown Iowa United States 50158
    178 Siouxland Regional Cancer Center Sioux City Iowa United States 51101
    179 Mercy Medical Center-Sioux City Sioux City Iowa United States 51104
    180 Saint Luke's Regional Medical Center Sioux City Iowa United States 51104
    181 Methodist West Hospital West Des Moines Iowa United States 50266-7700
    182 Mercy Medical Center-West Lakes West Des Moines Iowa United States 50266
    183 Cancer Center of Kansas - Chanute Chanute Kansas United States 66720
    184 Cancer Center of Kansas - Dodge City Dodge City Kansas United States 67801
    185 Cancer Center of Kansas - El Dorado El Dorado Kansas United States 67042
    186 Cancer Center of Kansas - Fort Scott Fort Scott Kansas United States 66701
    187 Cancer Center of Kansas-Independence Independence Kansas United States 67301
    188 Cancer Center of Kansas-Kingman Kingman Kansas United States 67068
    189 Lawrence Memorial Hospital Lawrence Kansas United States 66044
    190 Cancer Center of Kansas-Liberal Liberal Kansas United States 67905
    191 Cancer Center of Kansas-Manhattan Manhattan Kansas United States 66502
    192 Cancer Center of Kansas - McPherson McPherson Kansas United States 67460
    193 Cancer Center of Kansas - Newton Newton Kansas United States 67114
    194 Cancer Center of Kansas - Parsons Parsons Kansas United States 67357
    195 Cancer Center of Kansas - Pratt Pratt Kansas United States 67124
    196 Cancer Center of Kansas - Salina Salina Kansas United States 67401
    197 Cancer Center of Kansas - Wellington Wellington Kansas United States 67152
    198 Associates In Womens Health Wichita Kansas United States 67208
    199 Cancer Center of Kansas-Wichita Medical Arts Tower Wichita Kansas United States 67208
    200 Cancer Center of Kansas - Wichita Wichita Kansas United States 67214
    201 Via Christi Regional Medical Center Wichita Kansas United States 67214
    202 Wichita NCI Community Oncology Research Program Wichita Kansas United States 67214
    203 Cancer Center of Kansas - Winfield Winfield Kansas United States 67156
    204 Oncology Hematology Care Inc-Crestview Crestview Hills Kentucky United States 41017
    205 LSU Health Baton Rouge-North Clinic Baton Rouge Louisiana United States 70805
    206 Hematology/Oncology Clinic LLP Baton Rouge Louisiana United States 70809
    207 Louisiana Hematology Oncology Associates LLC Baton Rouge Louisiana United States 70809
    208 Mary Bird Perkins Cancer Center Baton Rouge Louisiana United States 70809
    209 Medical Oncology LLC Baton Rouge Louisiana United States 70809
    210 Mary Bird Cancer Center/Saint Tammany Parish Covington Louisiana United States 70433
    211 Mary Bird Perkins Cancer Center/Terrebonne General Medical Center Houma Louisiana United States 70360
    212 Tulane University Health Sciences Center New Orleans Louisiana United States 70112
    213 Harold Alfond Center for Cancer Care Augusta Maine United States 04330
    214 Eastern Maine Medical Center Bangor Maine United States 04401
    215 Central Maine Medical Center Lewiston Maine United States 04240
    216 Penobscot Bay Medical Center Rockport Maine United States 04856
    217 Peninsula Regional Medical Center Salisbury Maryland United States 21801
    218 Beverly Hospital Beverly Massachusetts United States 01915
    219 Boston Medical Center Boston Massachusetts United States 02118
    220 Lahey Hospital and Medical Center Burlington Massachusetts United States 01805
    221 Addison Gilbert Hospital Gloucester Massachusetts United States 01930
    222 Bixby Medical Center Adrian Michigan United States 49221
    223 Hickman Cancer Center Adrian Michigan United States 49221
    224 Saint Joseph Mercy Hospital Ann Arbor Michigan United States 48106-0995
    225 Michigan Cancer Research Consortium NCORP Ann Arbor Michigan United States 48106
    226 Beaumont Hospital-Dearborn Dearborn Michigan United States 48124
    227 Wayne State University/Karmanos Cancer Institute Detroit Michigan United States 48201
    228 Henry Ford Hospital Detroit Michigan United States 48202
    229 Saint John Hospital and Medical Center Detroit Michigan United States 48236
    230 Green Bay Oncology - Escanaba Escanaba Michigan United States 49829
    231 Weisberg Cancer Treatment Center Farmington Hills Michigan United States 48334
    232 Hurley Medical Center Flint Michigan United States 48502
    233 Genesys Hurley Cancer Institute Flint Michigan United States 48503
    234 Green Bay Oncology - Iron Mountain Iron Mountain Michigan United States 49801
    235 Allegiance Health Jackson Michigan United States 49201
    236 Borgess Medical Center Kalamazoo Michigan United States 49001
    237 Bronson Methodist Hospital Kalamazoo Michigan United States 49007
    238 West Michigan Cancer Center Kalamazoo Michigan United States 49007
    239 Sparrow Hospital Lansing Michigan United States 48912
    240 Saint Mary Mercy Hospital Livonia Michigan United States 48154
    241 Mercy Memorial Hospital Monroe Michigan United States 48162
    242 Toledo Clinic Cancer Centers-Monroe Monroe Michigan United States 48162
    243 Saint Joseph Mercy Oakland Pontiac Michigan United States 48341
    244 Lake Huron Medical Center Port Huron Michigan United States 48060
    245 Saint Mary's of Michigan Saginaw Michigan United States 48601
    246 Providence Hospital-Southfield Cancer Center Southfield Michigan United States 48075
    247 Saint John Macomb-Oakland Hospital Warren Michigan United States 48093
    248 Sanford Clinic North-Bemidgi Bemidji Minnesota United States 56601
    249 Fairview Ridges Hospital Burnsville Minnesota United States 55337
    250 Mercy Hospital Coon Rapids Minnesota United States 55433
    251 Fairview-Southdale Hospital Edina Minnesota United States 55435
    252 Unity Hospital Fridley Minnesota United States 55432
    253 Hutchinson Area Health Care Hutchinson Minnesota United States 55350
    254 Minnesota Oncology Hematology PA-Maplewood Maplewood Minnesota United States 55109
    255 Saint John's Hospital - Healtheast Maplewood Minnesota United States 55109
    256 Abbott-Northwestern Hospital Minneapolis Minnesota United States 55407
    257 Hennepin County Medical Center Minneapolis Minnesota United States 55415
    258 Health Partners Inc Minneapolis Minnesota United States 55454
    259 New Ulm Medical Center New Ulm Minnesota United States 56073
    260 North Memorial Medical Health Center Robbinsdale Minnesota United States 55422
    261 Mayo Clinic Rochester Minnesota United States 55905
    262 Metro Minnesota Community Oncology Research Consortium Saint Louis Park Minnesota United States 55416
    263 Park Nicollet Clinic - Saint Louis Park Saint Louis Park Minnesota United States 55416
    264 Regions Hospital Saint Paul Minnesota United States 55101
    265 United Hospital Saint Paul Minnesota United States 55102
    266 Saint Francis Regional Medical Center Shakopee Minnesota United States 55379
    267 Lakeview Hospital Stillwater Minnesota United States 55082
    268 Ridgeview Medical Center Waconia Minnesota United States 55387
    269 Rice Memorial Hospital Willmar Minnesota United States 56201
    270 Minnesota Oncology Hematology PA-Woodbury Woodbury Minnesota United States 55125
    271 University of Mississippi Medical Center Jackson Mississippi United States 39216
    272 Central Care Cancer Center-Carrie J Babb Cancer Center Bolivar Missouri United States 65613
    273 Parkland Health Center-Bonne Terre Bonne Terre Missouri United States 63628
    274 CoxHealth Cancer Center Branson Missouri United States 65616
    275 Saint Francis Medical Center Cape Girardeau Missouri United States 63703
    276 Southeast Cancer Center Cape Girardeau Missouri United States 63703
    277 Saint Luke's Hospital Chesterfield Missouri United States 63017
    278 Capital Region Medical Center-Goldschmidt Cancer Center Jefferson City Missouri United States 65109
    279 Freeman Health System Joplin Missouri United States 64804
    280 Delbert Day Cancer Institute at PCRMC Rolla Missouri United States 65401
    281 Saint John's Clinic-Rolla-Cancer and Hematology Rolla Missouri United States 65401
    282 Saint Louis Cancer and Breast Institute-South City Saint Louis Missouri United States 63109
    283 Missouri Baptist Medical Center Saint Louis Missouri United States 63131
    284 Mercy Hospital Saint Louis Saint Louis Missouri United States 63141
    285 Sainte Genevieve County Memorial Hospital Sainte Genevieve Missouri United States 63670
    286 Cancer Research for the Ozarks NCORP Springfield Missouri United States 65804
    287 Mercy Hospital Springfield Springfield Missouri United States 65804
    288 CoxHealth South Hospital Springfield Missouri United States 65807
    289 Missouri Baptist Sullivan Hospital Sullivan Missouri United States 63080
    290 Missouri Baptist Outpatient Center-Sunset Hills Sunset Hills Missouri United States 63127
    291 Billings Clinic Cancer Center Billings Montana United States 59101
    292 Montana Cancer Consortium NCORP Billings Montana United States 59101
    293 Saint Vincent Healthcare Billings Montana United States 59101
    294 Bozeman Deaconess Hospital Bozeman Montana United States 59715
    295 Saint James Community Hospital and Cancer Treatment Center Butte Montana United States 59701
    296 Benefis Healthcare- Sletten Cancer Institute Great Falls Montana United States 59405
    297 Saint Peter's Community Hospital Helena Montana United States 59601
    298 Kalispell Regional Medical Center Kalispell Montana United States 59901
    299 Saint Patrick Hospital - Community Hospital Missoula Montana United States 59802
    300 Community Medical Hospital Missoula Montana United States 59804
    301 Cancer and Blood Specialists-Henderson Henderson Nevada United States 89052
    302 Comprehensive Cancer Centers of Nevada - Henderson Henderson Nevada United States 89052
    303 Las Vegas Cancer Center-Henderson Henderson Nevada United States 89052
    304 21st Century Oncology - Henderson Henderson Nevada United States 89074
    305 Comprehensive Cancer Centers of Nevada-Southeast Henderson Henderson Nevada United States 89074
    306 University Medical Center of Southern Nevada Las Vegas Nevada United States 89102
    307 Cancer and Blood Specialists-Shadow Las Vegas Nevada United States 89106
    308 Nevada Cancer Research Foundation CCOP Las Vegas Nevada United States 89106
    309 Radiation Oncology Centers of Nevada Central Las Vegas Nevada United States 89106
    310 21st Century Oncology Las Vegas Nevada United States 89109
    311 HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway Las Vegas Nevada United States 89109
    312 HealthCare Partners Medical Group Oncology/Hematology-San Martin Las Vegas Nevada United States 89113
    313 Radiation Oncology Centers of Nevada Southeast Las Vegas Nevada United States 89119
    314 Cancer Therapy and Integrative Medicine Las Vegas Nevada United States 89121
    315 Cancer and Blood Specialists-Tenaya Las Vegas Nevada United States 89128
    316 Comprehensive Cancer Centers of Nevada - Northwest Las Vegas Nevada United States 89128
    317 HealthCare Partners Medical Group Oncology/Hematology-Tenaya Las Vegas Nevada United States 89128
    318 Comprehensive Cancer Centers of Nevada-Summerlin Las Vegas Nevada United States 89144
    319 Las Vegas Cancer Center-Medical Center Las Vegas Nevada United States 89148-2405
    320 21st Century Oncology - Fort Apache Las Vegas Nevada United States 89148
    321 Cancer and Blood Specialists-Fort Apache Las Vegas Nevada United States 89148
    322 Comprehensive Cancer Centers of Nevada Las Vegas Nevada United States 89148
    323 HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills Las Vegas Nevada United States 89149
    324 Comprehensive Cancer Centers of Nevada - Central Valley Las Vegas Nevada United States 89169
    325 21st Century Oncology - Vegas Tenaya Las Vegas Nevada United States 89182
    326 Inspira Medical Center Vineland Vineland New Jersey United States 08360
    327 Inspira Medical Center Woodbury Woodbury New Jersey United States 08096
    328 Orange Regional Medical Center Middletown New York United States 10940
    329 Randolph Hospital Asheboro North Carolina United States 27203
    330 Cone Health Cancer Center at Alamance Regional Burlington North Carolina United States 27215
    331 UNC Lineberger Comprehensive Cancer Center Chapel Hill North Carolina United States 27599
    332 Southeastern Medical Oncology Center-Clinton Clinton North Carolina United States 28328
    333 Southeastern Medical Oncology Center-Goldsboro Goldsboro North Carolina United States 27534
    334 Wayne Memorial Hospital Goldsboro North Carolina United States 27534
    335 Cone Health Cancer Center Greensboro North Carolina United States 27403
    336 Hendersonville Hematology and Oncology at Pardee Hendersonville North Carolina United States 28791
    337 Margaret R Pardee Memorial Hospital Hendersonville North Carolina United States 28791
    338 Southeastern Medical Oncology Center-Jacksonville Jacksonville North Carolina United States 28546
    339 Kinston Medical Specialists PA Kinston North Carolina United States 28501
    340 Cone Heath Cancer Center at Mebane Mebane North Carolina United States 27302
    341 Annie Penn Memorial Hospital Reidsville North Carolina United States 27320
    342 Iredell Memorial Hospital Statesville North Carolina United States 28677
    343 Southeastern Medical Oncology Center-Wilson Wilson North Carolina United States 27893
    344 Wake Forest University Health Sciences Winston-Salem North Carolina United States 27157
    345 Sanford Bismarck Medical Center Bismarck North Dakota United States 58501
    346 Roger Maris Cancer Center Fargo North Dakota United States 58122
    347 Sanford Clinic North-Fargo Fargo North Dakota United States 58122
    348 Sanford Medical Center-Fargo Fargo North Dakota United States 58122
    349 Strecker Cancer Center-Belpre Belpre Ohio United States 45714
    350 Toledo Clinic Cancer Centers-Bowling Green Bowling Green Ohio United States 43402
    351 Aultman Health Foundation Canton Ohio United States 44710
    352 Miami Valley Hospital South Centerville Ohio United States 45459
    353 Adena Regional Medical Center Chillicothe Ohio United States 45601
    354 Oncology Hematology Care Inc-Eden Park Cincinnati Ohio United States 45202
    355 Oncology Hematology Care Inc-Mercy West Cincinnati Ohio United States 45211
    356 Oncology Hematology Care Inc - Anderson Cincinnati Ohio United States 45230
    357 Oncology Hematology Care Inc-Kenwood Cincinnati Ohio United States 45236
    358 Oncology Hematology Care Inc-Blue Ash Cincinnati Ohio United States 45242
    359 Mount Carmel East Hospital Columbus Ohio United States 43213
    360 Columbus Oncology and Hematology Associates Inc Columbus Ohio United States 43214
    361 Riverside Methodist Hospital Columbus Ohio United States 43214
    362 Columbus NCI Community Oncology Research Program Columbus Ohio United States 43215
    363 Grant Medical Center Columbus Ohio United States 43215
    364 The Mark H Zangmeister Center Columbus Ohio United States 43219
    365 Mount Carmel Health Center West Columbus Ohio United States 43222
    366 Doctors Hospital Columbus Ohio United States 43228
    367 Good Samaritan Hospital - Dayton Dayton Ohio United States 45406
    368 Miami Valley Hospital Dayton Ohio United States 45409
    369 Samaritan North Health Center Dayton Ohio United States 45415
    370 Dayton NCI Community Oncology Research Program Dayton Ohio United States 45420
    371 Delaware Health Center-Grady Cancer Center Delaware Ohio United States 43015
    372 Delaware Radiation Oncology Delaware Ohio United States 43015
    373 Grady Memorial Hospital Delaware Ohio United States 43015
    374 Oncology Hematology Care Inc-Healthplex Fairfield Ohio United States 45014
    375 Blanchard Valley Hospital Findlay Ohio United States 45840
    376 Atrium Medical Center-Middletown Regional Hospital Franklin Ohio United States 45005-1066
    377 Wayne Hospital Greenville Ohio United States 45331
    378 Kettering Medical Center Kettering Ohio United States 45429
    379 Fairfield Medical Center Lancaster Ohio United States 43130
    380 Lancaster Radiation Oncology Lancaster Ohio United States 43130
    381 Lima Memorial Hospital Lima Ohio United States 45804
    382 Marietta Memorial Hospital Marietta Ohio United States 45750
    383 OneHealth Marion General Hospital Marion Ohio United States 43302
    384 Toledo Clinic Cancer Centers-Maumee Maumee Ohio United States 43537
    385 Toledo Radiation Oncology at Northwest Ohio Onocolgy Center Maumee Ohio United States 43537
    386 Knox Community Hospital Mount Vernon Ohio United States 43050
    387 Licking Memorial Hospital Newark Ohio United States 43055
    388 Newark Radiation Oncology Newark Ohio United States 43055
    389 Saint Charles Hospital Oregon Ohio United States 43616
    390 Toledo Clinic Cancer Centers-Oregon Oregon Ohio United States 43616
    391 Southern Ohio Medical Center Portsmouth Ohio United States 45662
    392 Springfield Regional Cancer Center Springfield Ohio United States 45504
    393 Springfield Regional Medical Center Springfield Ohio United States 45505
    394 Flower Hospital Sylvania Ohio United States 43560
    395 Mercy Hospital of Tiffin Tiffin Ohio United States 44883
    396 The Toledo Hospital/Toledo Children's Hospital Toledo Ohio United States 43606
    397 Saint Vincent Mercy Medical Center Toledo Ohio United States 43608
    398 University of Toledo Toledo Ohio United States 43614
    399 Toledo Community Hospital Oncology Program CCOP Toledo Ohio United States 43617
    400 Mercy Saint Anne Hospital Toledo Ohio United States 43623
    401 Toledo Clinic Cancer Centers-Toledo Toledo Ohio United States 43623
    402 Upper Valley Medical Center Troy Ohio United States 45373
    403 Fulton County Health Center Wauseon Ohio United States 43567
    404 Saint Ann's Hospital Westerville Ohio United States 43081
    405 Wright-Patterson Medical Center Wright-Patterson Air Force Base Ohio United States 45433-5529
    406 Genesis Healthcare System Cancer Care Center Zanesville Ohio United States 43701
    407 University of Oklahoma Health Sciences Center Oklahoma City Oklahoma United States 73104
    408 Bryn Mawr Hospital Bryn Mawr Pennsylvania United States 19010
    409 Geisinger Medical Center Danville Pennsylvania United States 17822
    410 Geisinger Medical Center-Cancer Center Hazleton Hazleton Pennsylvania United States 18201
    411 Geisinger Medical Oncology-Lewisburg Lewisburg Pennsylvania United States 17837
    412 Lewistown Hospital Lewistown Pennsylvania United States 17044
    413 Riddle Memorial Hospital Media Pennsylvania United States 19063
    414 Paoli Memorial Hospital Paoli Pennsylvania United States 19301
    415 University of Pennsylvania/Abramson Cancer Center Philadelphia Pennsylvania United States 19104
    416 Geisinger Medical Oncology-Pottsville Pottsville Pennsylvania United States 17901
    417 Penn State Health Saint Joseph Medical Center Reading Pennsylvania United States 19605
    418 Grand View Hospital Sellersville Pennsylvania United States 18960
    419 Geisinger Medical Group State College Pennsylvania United States 16801
    420 Reading Hospital West Reading Pennsylvania United States 19611
    421 Geisinger Wyoming Valley/Henry Cancer Center Wilkes-Barre Pennsylvania United States 18711
    422 Lankenau Medical Center Wynnewood Pennsylvania United States 19096
    423 Main Line Health NCORP Wynnewood Pennsylvania United States 19096
    424 AnMed Health Cancer Center Anderson South Carolina United States 29621
    425 McLeod Regional Medical Center Florence South Carolina United States 29506
    426 Rapid City Regional Hospital Rapid City South Dakota United States 57701
    427 Sanford Cancer Center-Oncology Clinic Sioux Falls South Dakota United States 57104
    428 Sanford USD Medical Center - Sioux Falls Sioux Falls South Dakota United States 57117-5134
    429 M D Anderson Cancer Center Houston Texas United States 77030
    430 Fredericksburg Oncology Inc Fredericksburg Virginia United States 22401
    431 Virginia Mason Medical Center Seattle Washington United States 98101
    432 Pacific Medical Center-First Hill Seattle Washington United States 98104
    433 Aurora Cancer Care-Southern Lakes VLCC Burlington Wisconsin United States 53105
    434 Marshfield Clinic-Chippewa Center Chippewa Falls Wisconsin United States 54729
    435 Marshfield Clinic Cancer Center at Sacred Heart Eau Claire Wisconsin United States 54701
    436 Sacred Heart Hospital Eau Claire Wisconsin United States 54701
    437 Aurora Health Center-Fond du Lac Fond Du Lac Wisconsin United States 54937
    438 Aurora Health Care Germantown Health Center Germantown Wisconsin United States 53022
    439 Aurora Cancer Care-Grafton Grafton Wisconsin United States 53024
    440 Green Bay Oncology at Saint Vincent Hospital Green Bay Wisconsin United States 54301-3526
    441 Saint Vincent Hospital Cancer Center Green Bay Green Bay Wisconsin United States 54301
    442 Green Bay Oncology Limited at Saint Mary's Hospital Green Bay Wisconsin United States 54303
    443 Saint Vincent Hospital Cancer Center at Saint Mary's Green Bay Wisconsin United States 54303
    444 Aurora BayCare Medical Center Green Bay Wisconsin United States 54311
    445 Mercy Health System Janesville Wisconsin United States 53547
    446 Aurora Cancer Care-Kenosha South Kenosha Wisconsin United States 53142
    447 Holy Family Memorial Hospital Manitowoc Wisconsin United States 54221
    448 Bay Area Medical Center Marinette Wisconsin United States 54143
    449 Vince Lombardi Cancer Clinic-Marinette Marinette Wisconsin United States 54143
    450 Marshfield Clinic Marshfield Wisconsin United States 54449
    451 Saint Joseph's Hospital Marshfield Wisconsin United States 54449
    452 Aurora Cancer Care-Milwaukee Milwaukee Wisconsin United States 53209
    453 Aurora Saint Luke's Medical Center Milwaukee Wisconsin United States 53215
    454 Aurora Sinai Medical Center Milwaukee Wisconsin United States 53233
    455 Marshfield Clinic-Minocqua Center Minocqua Wisconsin United States 54548
    456 ProHealth D N Greenwald Center Mukwonago Wisconsin United States 53149
    457 Cancer Center of Western Wisconsin New Richmond Wisconsin United States 54017
    458 ProHealth Oconomowoc Memorial Hospital Oconomowoc Wisconsin United States 53066
    459 Green Bay Oncology - Oconto Falls Oconto Falls Wisconsin United States 54154
    460 Vince Lombardi Cancer Clinic - Oshkosh Oshkosh Wisconsin United States 54904
    461 Aurora Cancer Care-Racine Racine Wisconsin United States 53406
    462 Marshfield Clinic at James Beck Cancer Center Rhinelander Wisconsin United States 54501
    463 Saint Mary's Hospital Rhinelander Wisconsin United States 54501
    464 Lakeview Medical Center-Marshfield Clinic Rice Lake Wisconsin United States 54868
    465 Marshfield Clinic-Rice Lake Center Rice Lake Wisconsin United States 54868
    466 HSHS Saint Nicholas Hospital Sheboygan Wisconsin United States 53081
    467 Vince Lombardi Cancer Clinic-Sheboygan Sheboygan Wisconsin United States 53081
    468 Marshfield Clinic Cancer Care at Saint Michael's Hospital Stevens Point Wisconsin United States 54481
    469 Saint Michael's Hospital Stevens Point Wisconsin United States 54481
    470 Green Bay Oncology - Sturgeon Bay Sturgeon Bay Wisconsin United States 54235
    471 Aurora Medical Center in Summit Summit Wisconsin United States 53066
    472 Vince Lombardi Cancer Clinic-Two Rivers Two Rivers Wisconsin United States 54241
    473 Aurora Cancer Care-Waukesha Waukesha Wisconsin United States 53188
    474 ProHealth Waukesha Memorial Hospital Waukesha Wisconsin United States 53188
    475 UW Cancer Center at ProHealth Care Waukesha Wisconsin United States 53188
    476 Marshfield Clinic-Wausau Center Wausau Wisconsin United States 54401
    477 Aurora Cancer Care-Milwaukee West Wauwatosa Wisconsin United States 53226
    478 Aurora West Allis Medical Center West Allis Wisconsin United States 53227
    479 Marshfield Clinic - Weston Center Weston Wisconsin United States 54476
    480 Saint Clare's Hospital Weston Wisconsin United States 54476
    481 Marshfield Clinic - Wisconsin Rapids Center Wisconsin Rapids Wisconsin United States 54494
    482 Rocky Mountain Oncology Casper Wyoming United States 82609
    483 Big Horn Basin Cancer Center Cody Wyoming United States 82414
    484 Billings Clinic-Cody Cody Wyoming United States 82414
    485 Welch Cancer Center Sheridan Wyoming United States 82801

    Sponsors and Collaborators

    • Southwest Oncology Group
    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Sikander Ailawadhi, Southwest Oncology Group

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Southwest Oncology Group
    ClinicalTrials.gov Identifier:
    NCT01903811
    Other Study ID Numbers:
    • S1304
    • NCI-2013-00796
    • PS1304_A07PAMDREVW01
    • SWOG-S1304
    • S1304
    • S1304
    • U10CA180888
    • U10CA032102
    First Posted:
    Jul 19, 2013
    Last Update Posted:
    Apr 14, 2020
    Last Verified:
    Apr 1, 2020

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Arm I (Dexamethasone, Low-dose Carfilzomib) Arm II (Dexamethasone, High-dose Carfilzomib)
    Arm/Group Description Patients receive dexamethasone IV and low-dose carfilzomib IV over 2-10 minutes on days 1, 2, 8, 9, 15, and 16. (Note that course 1 is given at a reduced dose.) Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients with progression cross-over to Arm II. Carfilzomib: Given IV Dexamethasone: Given IV Laboratory Biomarker Analysis: Correlative studies Patients receive dexamethasone IV and high-dose carfilzomib IV over 30 minutes on days 1, 2, 8, 9, 15, and 16. (Note that course 1 is given at a reduced dose over 2-10 minutes.) Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Carfilzomib: Given IV Dexamethasone: Given IV Laboratory Biomarker Analysis: Correlative studies
    Period Title: Overall Study
    STARTED 72 71
    Crossover to Arm II 16 0
    COMPLETED 64 57
    NOT COMPLETED 8 14

    Baseline Characteristics

    Arm/Group Title Arm I (Dexamethasone, Low-dose Carfilzomib) Arm II (Dexamethasone, High-dose Carfilzomib) Total
    Arm/Group Description Patients receive dexamethasone IV and low-dose carfilzomib IV over 2-10 minutes on days 1, 2, 8, 9, 15, and 16. (Note that course 1 is given at a reduced dose.) Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients with progression cross-over to Arm II. Carfilzomib: Given IV Dexamethasone: Given IV Laboratory Biomarker Analysis: Correlative studies Patients receive dexamethasone IV and high-dose carfilzomib IV over 30 minutes on days 1, 2, 8, 9, 15, and 16. (Note that course 1 is given at a reduced dose over 2-10 minutes.) Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Carfilzomib: Given IV Dexamethasone: Given IV Laboratory Biomarker Analysis: Correlative studies Total of all reporting groups
    Overall Participants 64 57 121
    Age, Customized (Count of Participants)
    Age >= 65
    31
    48.4%
    32
    56.1%
    63
    52.1%
    Age < 65
    33
    51.6%
    25
    43.9%
    58
    47.9%
    Sex: Female, Male (Count of Participants)
    Female
    31
    48.4%
    24
    42.1%
    55
    45.5%
    Male
    33
    51.6%
    33
    57.9%
    66
    54.5%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    1
    1.6%
    0
    0%
    1
    0.8%
    Asian
    1
    1.6%
    4
    7%
    5
    4.1%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    11
    17.2%
    8
    14%
    19
    15.7%
    White
    51
    79.7%
    41
    71.9%
    92
    76%
    More than one race
    0
    0%
    1
    1.8%
    1
    0.8%
    Unknown or Not Reported
    0
    0%
    3
    5.3%
    3
    2.5%
    Zubrod performance status > 1 (Count of Participants)
    Count of Participants [Participants]
    2
    3.1%
    3
    5.3%
    5
    4.1%
    Beta-2-microglobulin >=3.5 mg/L (Count of Participants)
    Count of Participants [Participants]
    36
    56.3%
    31
    54.4%
    67
    55.4%
    CRP >= 8 mg/L (Count of Participants)
    Count of Participants [Participants]
    6
    9.4%
    6
    10.5%
    12
    9.9%
    Creatinine >= 2 mg/dl (Count of Participants)
    Count of Participants [Participants]
    1
    1.6%
    0
    0%
    1
    0.8%
    Creatinine clearance < 60 ml/min (Count of Participants)
    Count of Participants [Participants]
    23
    35.9%
    18
    31.6%
    41
    33.9%
    LDH >= 190 U/L (Count of Participants)
    Count of Participants [Participants]
    31
    48.4%
    26
    45.6%
    57
    47.1%
    Albumin < 3.5 g/dl (Count of Participants)
    Count of Participants [Participants]
    16
    25%
    14
    24.6%
    30
    24.8%
    ISS disease stage: Stage 1 (Count of Participants)
    Count of Participants [Participants]
    20
    31.3%
    22
    38.6%
    42
    34.7%
    ISS disease stage: Stage 2 (Count of Participants)
    Count of Participants [Participants]
    30
    46.9%
    19
    33.3%
    49
    40.5%
    ISS disease stage: Stage 3 (Count of Participants)
    Count of Participants [Participants]
    14
    21.9%
    16
    28.1%
    30
    24.8%
    Hemoglobin <10 g/dL (Count of Participants)
    Count of Participants [Participants]
    15
    23.4%
    6
    10.5%
    21
    17.4%
    Platelet count < 150 x 10^9/L (Count of Participants)
    Count of Participants [Participants]
    1
    1.6%
    1
    1.8%
    2
    1.7%
    4-6 Prior lines of therapy (Count of Participants)
    Count of Participants [Participants]
    14
    21.9%
    15
    26.3%
    29
    24%
    Refractory to Bortezomib (Count of Participants)
    Count of Participants [Participants]
    32
    50%
    28
    49.1%
    60
    49.6%
    Serum M spike >3 g/dL (Count of Participants)
    Count of Participants [Participants]
    13
    20.3%
    6
    10.5%
    19
    15.7%
    Bone marrow plasma cells > 60% (Count of Participants)
    Count of Participants [Participants]
    14
    21.9%
    11
    19.3%
    25
    20.7%
    sLFC Ratio >=100 (Count of Participants)
    Count of Participants [Participants]
    24
    37.5%
    19
    33.3%
    43
    35.5%
    Myeloma isotype: IgG (Count of Participants)
    Count of Participants [Participants]
    36
    56.3%
    24
    42.1%
    60
    49.6%
    Myeloma isotype: IgA (Count of Participants)
    Count of Participants [Participants]
    5
    7.8%
    12
    21.1%
    17
    14%
    Myeloma isotype: light chain only (Count of Participants)
    Count of Participants [Participants]
    9
    14.1%
    8
    14%
    17
    14%

    Outcome Measures

    1. Primary Outcome
    Title Progression-free Survival
    Description Assessed in each arm using the method of Kaplan Meier and compared between arms using the stratified long-rank test. Progression is defined using the International Uniform Response Criteria for Multiple Myeloma as new or increase in size of existing bone lesions or soft tissue plasmacytomas; or development of hypercalcemia attributable solely to MM; or ≥ 25% increase from baseline or lowest response level of either serum M protein, urine M protein, difference in involved & uninvolved serum free light chain level or bone marrow plasma cell percentage.
    Time Frame From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 2 years

    Outcome Measure Data

    Analysis Population Description
    Group of participants that were eligible and analyzable per protocol.
    Arm/Group Title Arm I (Dexamethasone, Low-dose Carfilzomib) Arm II (Dexamethasone, High-dose Carfilzomib)
    Arm/Group Description Patients receive 20 mg dexamethasone IV and low-dose (27 mg/m^2) carfilzomib IV over 2-10 minutes on days 1, 2, 8, 9, 15, and 16. (Note that course 1 is given at a reduced dose of 20 mg/m^2.) Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients with progression cross-over to Arm II. Carfilzomib: Given IV Dexamethasone: Given IV Laboratory Biomarker Analysis: Correlative studies Patients receive 20 mg dexamethasone IV and high-dose (56 mg/m^2) carfilzomib IV over 30 minutes on days 1, 2, 8, 9, 15, and 16. (Note that course 1 is given at a reduced dose of 20 mg/m^2 over 2-10 minutes.) Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Carfilzomib: Given IV Dexamethasone: Given IV Laboratory Biomarker Analysis: Correlative studies
    Measure Participants 64 57
    Median (95% Confidence Interval) [months]
    5
    8
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm I (Dexamethasone, Low-dose Carfilzomib), Arm II (Dexamethasone, High-dose Carfilzomib)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.384
    Comments Stratified by pre-specified randomization stratification factors: 1 - 3 prior therapies vs. 4-6 prior therapies and refractory to bortezomib vs. not refractory to bortezomib.
    Method Log Rank
    Comments One-sided stratified log rank test
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.061
    Confidence Interval (2-Sided) 80%
    0.821 to 1.370
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Overall Survival
    Description Assessed in each arm using the method of Kaplan Meier and compared between arms using the stratified log-rank test.
    Time Frame From date of registration to date of death due to any cause, assessed up to 3 years

    Outcome Measure Data

    Analysis Population Description
    Participants that were eligible and analyzable per protocol.
    Arm/Group Title Arm I (Dexamethasone, Low-dose Carfilzomib) Arm II (Dexamethasone, High-dose Carfilzomib)
    Arm/Group Description Patients receive 20 mg dexamethasone IV and low-dose (27 mg/m^2) carfilzomib IV over 2-10 minutes on days 1, 2, 8, 9, 15, and 16. (Note that course 1 is given at a reduced dose of 20 mg/m^2.) Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients with progression cross-over to Arm II. Carfilzomib: Given IV Dexamethasone: Given IV Laboratory Biomarker Analysis: Correlative studies Patients receive 20 mg dexamethasone IV and high-dose (56 mg/m^2) carfilzomib IV over 30 minutes on days 1, 2, 8, 9, 15, and 16. (Note that course 1 is given at a reduced dose of 20 mg/m^2 over 2-10 minutes.) Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Carfilzomib: Given IV Dexamethasone: Given IV Laboratory Biomarker Analysis: Correlative studies
    Measure Participants 64 57
    Median (95% Confidence Interval) [months]
    26
    22
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm I (Dexamethasone, Low-dose Carfilzomib), Arm II (Dexamethasone, High-dose Carfilzomib)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.284
    Comments Stratified by pre-specified randomization stratification factors: 1 - 3 prior therapies vs. 4-6 prior therapies and refractory to bortezomib vs. not refractory to bortezomib.
    Method Log Rank
    Comments One-sided stratified log rank test
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.149
    Confidence Interval (2-Sided) 80%
    0.841 to 1.571
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Best Overall Response - Partial Response (PR), Very Good Partial Response (VGPR), Unconfirmed PR (uPR), Stable Disease (SD) Progression (PROG)
    Description Per International Uniform Response Criteria for Multiple Myeloma PR- ≥ 50% reduction in size of soft tissue plasmacytomas & plasma cells; ≥ 50% decrease in serum & reduction in urine M protein ≥ 90% or to < 200 mg/24hr or ≥ 50% decrease in difference in uninvolved & involved serum free light chain levels; VGPR- PR + Serum and urine M proteins detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M protein & urine M protein < 100 mg/24 hrs; uPR- 1 objective status of PR, but confirmation studies are not done, or do not meet the requirements necessary to confirm response; SD- does not meet criteria for sCR, CR, VGPR, PR or PROG; PROG- new or increase in size of existing bone lesions or soft tissue plasmacytomas/ development of hypercalcemia attributable solely to MM/ ≥ 25% increase from baseline/ lowest response level of either serum or Urine M protein, difference in involved & uninvolved serum free light chain level or bone marrow plasma cell percentage.
    Time Frame From date of registration to date of best response while on study treatment

    Outcome Measure Data

    Analysis Population Description
    This population includes eligible and analyzable patients who had a follow-up response assessment.
    Arm/Group Title Arm I (Dexamethasone, Low-dose Carfilzomib) Arm II (Dexamethasone, High-dose Carfilzomib)
    Arm/Group Description Patients receive 20 mg dexamethasone IV and low-dose (27 mg/m^2) carfilzomib IV over 2-10 minutes on days 1, 2, 8, 9, 15, and 16. (Note that course 1 is given at a reduced dose of 20 mg/m^2.) Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients with progression cross-over to Arm II. Carfilzomib: Given IV Dexamethasone: Given IV Laboratory Biomarker Analysis: Correlative studies Patients receive 20 mg dexamethasone IV and high-dose (56 mg/m^2) carfilzomib IV over 30 minutes on days 1, 2, 8, 9, 15, and 16. (Note that course 1 is given at a reduced dose of 20 mg/m^2 over 2-10 minutes.) Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Carfilzomib: Given IV Dexamethasone: Given IV Laboratory Biomarker Analysis: Correlative studies
    Measure Participants 59 53
    Very Good Partial Response (VGPR)
    5
    7.8%
    14
    24.6%
    Partial Response (PR)
    18
    28.1%
    11
    19.3%
    Unconfirmed Partial Response (uPR)
    0
    0%
    2
    3.5%
    Stable Disease (SD)
    24
    37.5%
    19
    33.3%
    Progressive Disease
    12
    18.8%
    7
    12.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm I (Dexamethasone, Low-dose Carfilzomib), Arm II (Dexamethasone, High-dose Carfilzomib)
    Comments Compare the rate of confirmed PR or better between treatment arms.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1130
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    4. Secondary Outcome
    Title Progression-free Survival of Crossover Group
    Description Assessed in the crossover arm using the method of Kaplan Meier. Progression is defined using the International Uniform Response Criteria for Multiple Myeloma as new or increase in size of existing bone lesions or soft tissue plasmacytomas; or development of hypercalcemia attributable solely to MM; or ≥ 25% increase from baseline or lowest response level of either serum M protein, urine M protein, difference in involved & uninvolved serum free light chain level or bone marrow plasma cell percentage.
    Time Frame From date of crossover to date of subsequent documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 3 years from randomization

    Outcome Measure Data

    Analysis Population Description
    Patients on Arm 1 that progress after the start of course 2 and prior to completion of 12 courses receive high dose carfilzomib
    Arm/Group Title Arm III (Crossover Group)
    Arm/Group Description Patients on Arm 1 that progress after the start of course 2 and prior to completion of 12 courses receive 20 mg dexamethasone IV and high-dose (56 mg/m^2) carfilzomib IV over 30 minutes on days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days for up to 12 additional courses in the absence of disease progression or unacceptable toxicity. Carfilzomib: Given IV Dexamethasone: Given IV Laboratory Biomarker Analysis: Correlative studies
    Measure Participants 16
    Median (95% Confidence Interval) [months]
    3
    5. Secondary Outcome
    Title Overall Survival Crossover Group
    Description Assessed in the crossover arm using the method of Kaplan Meier.
    Time Frame From date of crossover to date of death due to any cause, assessed up to 3 years from randomization

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Crossover Arm
    Arm/Group Description Patients on Arm 1 that progress after the start of course 2 and prior to completion of 12 courses receive 20 mg dexamethasone IV and high-dose (56 mg/m^2) carfilzomib IV over 30 minutes on days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days for up to 12 additional courses in the absence of disease progression or unacceptable toxicity. Carfilzomib: Given IV Dexamethasone: Given IV Laboratory Biomarker Analysis: Correlative studies
    Measure Participants 16
    Median (95% Confidence Interval) [months]
    15
    6. Other Pre-specified Outcome
    Title Gene Expression Profiles
    Description Bone marrow compared to that of an aspirate taken at the site of the EMP. Data will be log-transformed before analysis. Exploratory analyses will examine underlying distributions using boxplots, density plots, scatter plots, etc. For differential expression analysis of the two sample types t-tests will be conducted on genes. False discovery rate will be used to control the average false positive proportions among selected genes. Genes will be ranked by their q-value and pathway analysis conducted upon selected genes to determine biological plausibility and relevance to molecular functionality.
    Time Frame Up to 3 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    7. Other Pre-specified Outcome
    Title Incidence of CR by PET, Defined as the Disappearance of All Focal Lesions and the Resolution of EMD
    Description Univariate and multivariate logistic regression will be used to determine the impact of biochemical CR on CR by PET. In the multivariate analysis adjustment for standard prognostic factors such as age, albumin, beta-2 microglobulin, serum creatinine, c-reactive protein and lactate dehydrogenase will be included.
    Time Frame Up to week 45

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description

    Adverse Events

    Time Frame For the duration of treatment, up to 12 cycles and maximum follow up of 3 years post-registration.
    Adverse Event Reporting Description Note that denominators differ from those reported in other Results sections as the AE data tables are pulled from the live database and thus reflect more current data while other Sections are based those data reported at the time of Primary Endpoint analyses.
    Arm/Group Title Arm I (Dexamethasone, Low-dose Carfilzomib) Arm II (Dexamethasone, High-dose Carfilzomib) Crossover Arm
    Arm/Group Description Patients receive dexamethasone and low dose carfilzomib. Includes all eligible and analyzable patients. Deaths for patients that registered Crossover arm are also counted in this arm. Patients receive dexamethasone and high dose carfilzomib. Includes all eligible and analyzable patients. Patients on Arm 1 that progress after the start of cycle 2 and prior to completion of 12 cycles receive high dose carfilzomib. Includes all eligible and analyzable patients. These patients are also included under "Arm I".
    All Cause Mortality
    Arm I (Dexamethasone, Low-dose Carfilzomib) Arm II (Dexamethasone, High-dose Carfilzomib) Crossover Arm
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 38/66 (57.6%) 40/57 (70.2%) 12/16 (75%)
    Serious Adverse Events
    Arm I (Dexamethasone, Low-dose Carfilzomib) Arm II (Dexamethasone, High-dose Carfilzomib) Crossover Arm
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 26/66 (39.4%) 27/57 (47.4%) 5/16 (31.3%)
    Blood and lymphatic system disorders
    Anemia 3/66 (4.5%) 6/57 (10.5%) 1/16 (6.3%)
    Febrile neutropenia 0/66 (0%) 1/57 (1.8%) 1/16 (6.3%)
    Cardiac disorders
    Acute coronary syndrome 0/66 (0%) 1/57 (1.8%) 0/16 (0%)
    Atrial flutter 0/66 (0%) 0/57 (0%) 1/16 (6.3%)
    Cardiac arrest 1/66 (1.5%) 0/57 (0%) 0/16 (0%)
    Chest pain - cardiac 1/66 (1.5%) 0/57 (0%) 0/16 (0%)
    Heart failure 2/66 (3%) 2/57 (3.5%) 0/16 (0%)
    Left ventricular systolic dysfunction 1/66 (1.5%) 0/57 (0%) 0/16 (0%)
    Restrictive cardiomyopathy 2/66 (3%) 0/57 (0%) 0/16 (0%)
    Sinus tachycardia 1/66 (1.5%) 0/57 (0%) 0/16 (0%)
    Supraventricular tachycardia 0/66 (0%) 0/57 (0%) 1/16 (6.3%)
    Eye disorders
    Blurred vision 2/66 (3%) 0/57 (0%) 0/16 (0%)
    Glaucoma 1/66 (1.5%) 0/57 (0%) 0/16 (0%)
    Gastrointestinal disorders
    Gastroesophageal reflux disease 0/66 (0%) 1/57 (1.8%) 0/16 (0%)
    Nausea 0/66 (0%) 1/57 (1.8%) 0/16 (0%)
    Vomiting 1/66 (1.5%) 1/57 (1.8%) 0/16 (0%)
    General disorders
    Chills 0/66 (0%) 1/57 (1.8%) 0/16 (0%)
    Death NOS 1/66 (1.5%) 1/57 (1.8%) 0/16 (0%)
    Edema limbs 1/66 (1.5%) 1/57 (1.8%) 0/16 (0%)
    Fatigue 2/66 (3%) 3/57 (5.3%) 0/16 (0%)
    Fever 2/66 (3%) 6/57 (10.5%) 0/16 (0%)
    Multi-organ failure 0/66 (0%) 1/57 (1.8%) 0/16 (0%)
    Non-cardiac chest pain 1/66 (1.5%) 1/57 (1.8%) 0/16 (0%)
    Sudden death NOS 1/66 (1.5%) 0/57 (0%) 0/16 (0%)
    Hepatobiliary disorders
    Cholecystitis 1/66 (1.5%) 0/57 (0%) 0/16 (0%)
    Infections and infestations
    Endocarditis infective 0/66 (0%) 1/57 (1.8%) 0/16 (0%)
    Infections and infestations-Other 2/66 (3%) 0/57 (0%) 0/16 (0%)
    Lung infection 3/66 (4.5%) 7/57 (12.3%) 1/16 (6.3%)
    Otitis media 1/66 (1.5%) 0/57 (0%) 0/16 (0%)
    Sepsis 2/66 (3%) 3/57 (5.3%) 2/16 (12.5%)
    Sinusitis 1/66 (1.5%) 0/57 (0%) 0/16 (0%)
    Urinary tract infection 1/66 (1.5%) 2/57 (3.5%) 0/16 (0%)
    Injury, poisoning and procedural complications
    Fall 1/66 (1.5%) 1/57 (1.8%) 0/16 (0%)
    Fracture 1/66 (1.5%) 1/57 (1.8%) 0/16 (0%)
    Injury, poison and procedural complications - Other 1/66 (1.5%) 0/57 (0%) 0/16 (0%)
    Investigations
    Creatinine increased 2/66 (3%) 2/57 (3.5%) 0/16 (0%)
    Ejection fraction decreased 2/66 (3%) 1/57 (1.8%) 0/16 (0%)
    Lymphocyte count decreased 2/66 (3%) 3/57 (5.3%) 0/16 (0%)
    Lymphocyte count increased 1/66 (1.5%) 0/57 (0%) 0/16 (0%)
    Neutrophil count decreased 1/66 (1.5%) 0/57 (0%) 1/16 (6.3%)
    Platelet count decreased 4/66 (6.1%) 7/57 (12.3%) 1/16 (6.3%)
    White blood cell decreased 1/66 (1.5%) 0/57 (0%) 1/16 (6.3%)
    Metabolism and nutrition disorders
    Anorexia 0/66 (0%) 1/57 (1.8%) 0/16 (0%)
    Dehydration 3/66 (4.5%) 0/57 (0%) 0/16 (0%)
    Hypercalcemia 1/66 (1.5%) 1/57 (1.8%) 0/16 (0%)
    Hyperglycemia 0/66 (0%) 2/57 (3.5%) 0/16 (0%)
    Hypoalbuminemia 0/66 (0%) 1/57 (1.8%) 0/16 (0%)
    Hypocalcemia 0/66 (0%) 2/57 (3.5%) 0/16 (0%)
    Hypokalemia 0/66 (0%) 1/57 (1.8%) 0/16 (0%)
    Hyponatremia 1/66 (1.5%) 3/57 (5.3%) 0/16 (0%)
    Hypophosphatemia 1/66 (1.5%) 0/57 (0%) 0/16 (0%)
    Tumor lysis syndrome 1/66 (1.5%) 0/57 (0%) 0/16 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/66 (0%) 1/57 (1.8%) 0/16 (0%)
    Back pain 0/66 (0%) 3/57 (5.3%) 0/16 (0%)
    Bone pain 1/66 (1.5%) 1/57 (1.8%) 0/16 (0%)
    Chest wall pain 2/66 (3%) 0/57 (0%) 0/16 (0%)
    Generalized muscle weakness 2/66 (3%) 1/57 (1.8%) 0/16 (0%)
    Muscle weakness lower limb 0/66 (0%) 2/57 (3.5%) 0/16 (0%)
    Myalgia 0/66 (0%) 1/57 (1.8%) 0/16 (0%)
    Pain in extremity 0/66 (0%) 2/57 (3.5%) 0/16 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms benign, malignant and unspecified - Other 1/66 (1.5%) 0/57 (0%) 1/16 (6.3%)
    Nervous system disorders
    Dizziness 0/66 (0%) 1/57 (1.8%) 0/16 (0%)
    Nervous system disorders-Other 1/66 (1.5%) 0/57 (0%) 0/16 (0%)
    Somnolence 0/66 (0%) 1/57 (1.8%) 0/16 (0%)
    Stroke 0/66 (0%) 2/57 (3.5%) 1/16 (6.3%)
    Syncope 0/66 (0%) 1/57 (1.8%) 0/16 (0%)
    Psychiatric disorders
    Confusion 0/66 (0%) 1/57 (1.8%) 0/16 (0%)
    Renal and urinary disorders
    Acute kidney injury 2/66 (3%) 2/57 (3.5%) 1/16 (6.3%)
    Chronic kidney disease 0/66 (0%) 1/57 (1.8%) 0/16 (0%)
    Hematuria 0/66 (0%) 2/57 (3.5%) 0/16 (0%)
    Renal and urinary disorders-Other 1/66 (1.5%) 1/57 (1.8%) 0/16 (0%)
    Renal calculi 0/66 (0%) 1/57 (1.8%) 0/16 (0%)
    Urinary retention 0/66 (0%) 1/57 (1.8%) 0/16 (0%)
    Respiratory, thoracic and mediastinal disorders
    Adult respiratory distress syndrome 0/66 (0%) 2/57 (3.5%) 0/16 (0%)
    Bronchopulmonary hemorrhage 0/66 (0%) 0/57 (0%) 1/16 (6.3%)
    Cough 1/66 (1.5%) 0/57 (0%) 0/16 (0%)
    Dyspnea 1/66 (1.5%) 4/57 (7%) 0/16 (0%)
    Epistaxis 0/66 (0%) 1/57 (1.8%) 0/16 (0%)
    Hiccups 0/66 (0%) 1/57 (1.8%) 0/16 (0%)
    Hypoxia 1/66 (1.5%) 3/57 (5.3%) 1/16 (6.3%)
    Pulmonary edema 1/66 (1.5%) 1/57 (1.8%) 0/16 (0%)
    Respiratory failure 2/66 (3%) 1/57 (1.8%) 0/16 (0%)
    Vascular disorders
    Hypertension 1/66 (1.5%) 1/57 (1.8%) 0/16 (0%)
    Hypotension 2/66 (3%) 1/57 (1.8%) 0/16 (0%)
    Other (Not Including Serious) Adverse Events
    Arm I (Dexamethasone, Low-dose Carfilzomib) Arm II (Dexamethasone, High-dose Carfilzomib) Crossover Arm
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 66/66 (100%) 55/57 (96.5%) 14/16 (87.5%)
    Blood and lymphatic system disorders
    Anemia 39/66 (59.1%) 38/57 (66.7%) 8/16 (50%)
    Cardiac disorders
    Cardiac disorders-Other 5/66 (7.6%) 2/57 (3.5%) 0/16 (0%)
    Chest pain - cardiac 1/66 (1.5%) 3/57 (5.3%) 1/16 (6.3%)
    Sinus bradycardia 4/66 (6.1%) 0/57 (0%) 0/16 (0%)
    Sinus tachycardia 7/66 (10.6%) 3/57 (5.3%) 0/16 (0%)
    Ear and labyrinth disorders
    Hearing impaired 1/66 (1.5%) 3/57 (5.3%) 0/16 (0%)
    Eye disorders
    Blurred vision 9/66 (13.6%) 11/57 (19.3%) 0/16 (0%)
    Watering eyes 1/66 (1.5%) 0/57 (0%) 1/16 (6.3%)
    Gastrointestinal disorders
    Abdominal pain 6/66 (9.1%) 8/57 (14%) 1/16 (6.3%)
    Bloating 0/66 (0%) 4/57 (7%) 0/16 (0%)
    Constipation 12/66 (18.2%) 14/57 (24.6%) 2/16 (12.5%)
    Diarrhea 20/66 (30.3%) 20/57 (35.1%) 2/16 (12.5%)
    Dry mouth 6/66 (9.1%) 7/57 (12.3%) 0/16 (0%)
    Dyspepsia 5/66 (7.6%) 7/57 (12.3%) 0/16 (0%)
    Gastroesophageal reflux disease 5/66 (7.6%) 1/57 (1.8%) 0/16 (0%)
    Mucositis oral 4/66 (6.1%) 4/57 (7%) 0/16 (0%)
    Nausea 25/66 (37.9%) 21/57 (36.8%) 5/16 (31.3%)
    Stomach pain 2/66 (3%) 3/57 (5.3%) 2/16 (12.5%)
    Vomiting 13/66 (19.7%) 9/57 (15.8%) 0/16 (0%)
    General disorders
    Chills 5/66 (7.6%) 5/57 (8.8%) 2/16 (12.5%)
    Edema face 5/66 (7.6%) 1/57 (1.8%) 1/16 (6.3%)
    Edema limbs 14/66 (21.2%) 9/57 (15.8%) 1/16 (6.3%)
    Fatigue 39/66 (59.1%) 33/57 (57.9%) 6/16 (37.5%)
    Fever 9/66 (13.6%) 5/57 (8.8%) 2/16 (12.5%)
    Flu like symptoms 5/66 (7.6%) 2/57 (3.5%) 1/16 (6.3%)
    Non-cardiac chest pain 4/66 (6.1%) 4/57 (7%) 0/16 (0%)
    Pain 13/66 (19.7%) 15/57 (26.3%) 1/16 (6.3%)
    Immune system disorders
    Allergic reaction 0/66 (0%) 0/57 (0%) 1/16 (6.3%)
    Immune system disorders-Other 1/66 (1.5%) 1/57 (1.8%) 1/16 (6.3%)
    Infections and infestations
    Infections and infestations-Other 5/66 (7.6%) 6/57 (10.5%) 0/16 (0%)
    Sinusitis 5/66 (7.6%) 1/57 (1.8%) 0/16 (0%)
    Skin infection 1/66 (1.5%) 0/57 (0%) 1/16 (6.3%)
    Upper respiratory infection 5/66 (7.6%) 7/57 (12.3%) 1/16 (6.3%)
    Injury, poisoning and procedural complications
    Bruising 5/66 (7.6%) 6/57 (10.5%) 0/16 (0%)
    Fracture 1/66 (1.5%) 2/57 (3.5%) 1/16 (6.3%)
    Investigations
    Alanine aminotransferase increased 1/66 (1.5%) 4/57 (7%) 0/16 (0%)
    Alkaline phosphatase increased 7/66 (10.6%) 3/57 (5.3%) 1/16 (6.3%)
    Aspartate aminotransferase increased 7/66 (10.6%) 8/57 (14%) 0/16 (0%)
    Blood bilirubin increased 8/66 (12.1%) 4/57 (7%) 0/16 (0%)
    Creatinine increased 15/66 (22.7%) 14/57 (24.6%) 2/16 (12.5%)
    Lymphocyte count decreased 18/66 (27.3%) 16/57 (28.1%) 4/16 (25%)
    Neutrophil count decreased 13/66 (19.7%) 14/57 (24.6%) 1/16 (6.3%)
    Platelet count decreased 28/66 (42.4%) 29/57 (50.9%) 5/16 (31.3%)
    Weight gain 7/66 (10.6%) 3/57 (5.3%) 1/16 (6.3%)
    Weight loss 5/66 (7.6%) 8/57 (14%) 0/16 (0%)
    White blood cell decreased 21/66 (31.8%) 24/57 (42.1%) 3/16 (18.8%)
    Metabolism and nutrition disorders
    Anorexia 12/66 (18.2%) 13/57 (22.8%) 0/16 (0%)
    Dehydration 3/66 (4.5%) 6/57 (10.5%) 1/16 (6.3%)
    Hypercalcemia 4/66 (6.1%) 2/57 (3.5%) 1/16 (6.3%)
    Hyperglycemia 17/66 (25.8%) 15/57 (26.3%) 1/16 (6.3%)
    Hyperkalemia 5/66 (7.6%) 2/57 (3.5%) 1/16 (6.3%)
    Hyperuricemia 5/66 (7.6%) 4/57 (7%) 1/16 (6.3%)
    Hypoalbuminemia 15/66 (22.7%) 15/57 (26.3%) 1/16 (6.3%)
    Hypocalcemia 6/66 (9.1%) 11/57 (19.3%) 0/16 (0%)
    Hypokalemia 13/66 (19.7%) 3/57 (5.3%) 2/16 (12.5%)
    Hypomagnesemia 9/66 (13.6%) 8/57 (14%) 0/16 (0%)
    Hyponatremia 9/66 (13.6%) 11/57 (19.3%) 1/16 (6.3%)
    Hypophosphatemia 5/66 (7.6%) 7/57 (12.3%) 1/16 (6.3%)
    Metabolism and nutrition disorders - Other, specify 2/66 (3%) 3/57 (5.3%) 1/16 (6.3%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 7/66 (10.6%) 11/57 (19.3%) 3/16 (18.8%)
    Back pain 24/66 (36.4%) 21/57 (36.8%) 4/16 (25%)
    Bone pain 8/66 (12.1%) 6/57 (10.5%) 0/16 (0%)
    Chest wall pain 2/66 (3%) 3/57 (5.3%) 0/16 (0%)
    Generalized muscle weakness 7/66 (10.6%) 8/57 (14%) 1/16 (6.3%)
    Musculoskeletal and connective tiss disorder - Other 2/66 (3%) 2/57 (3.5%) 1/16 (6.3%)
    Myalgia 8/66 (12.1%) 5/57 (8.8%) 1/16 (6.3%)
    Neck pain 4/66 (6.1%) 2/57 (3.5%) 0/16 (0%)
    Pain in extremity 16/66 (24.2%) 15/57 (26.3%) 3/16 (18.8%)
    Nervous system disorders
    Dizziness 13/66 (19.7%) 12/57 (21.1%) 1/16 (6.3%)
    Dysgeusia 3/66 (4.5%) 4/57 (7%) 1/16 (6.3%)
    Headache 20/66 (30.3%) 18/57 (31.6%) 2/16 (12.5%)
    Nervous system disorders-Other 1/66 (1.5%) 3/57 (5.3%) 0/16 (0%)
    Paresthesia 5/66 (7.6%) 4/57 (7%) 0/16 (0%)
    Peripheral motor neuropathy 0/66 (0%) 5/57 (8.8%) 0/16 (0%)
    Peripheral sensory neuropathy 20/66 (30.3%) 18/57 (31.6%) 4/16 (25%)
    Psychiatric disorders
    Anxiety 10/66 (15.2%) 9/57 (15.8%) 2/16 (12.5%)
    Confusion 4/66 (6.1%) 3/57 (5.3%) 2/16 (12.5%)
    Depression 8/66 (12.1%) 3/57 (5.3%) 2/16 (12.5%)
    Insomnia 19/66 (28.8%) 20/57 (35.1%) 3/16 (18.8%)
    Renal and urinary disorders
    Acute kidney injury 3/66 (4.5%) 2/57 (3.5%) 1/16 (6.3%)
    Chronic kidney disease 2/66 (3%) 3/57 (5.3%) 1/16 (6.3%)
    Proteinuria 6/66 (9.1%) 2/57 (3.5%) 0/16 (0%)
    Renal and urinary disorders-Other 3/66 (4.5%) 1/57 (1.8%) 1/16 (6.3%)
    Urinary frequency 2/66 (3%) 4/57 (7%) 0/16 (0%)
    Respiratory, thoracic and mediastinal disorders
    Cough 22/66 (33.3%) 17/57 (29.8%) 2/16 (12.5%)
    Dyspnea 22/66 (33.3%) 27/57 (47.4%) 3/16 (18.8%)
    Epistaxis 1/66 (1.5%) 3/57 (5.3%) 0/16 (0%)
    Nasal congestion 2/66 (3%) 3/57 (5.3%) 0/16 (0%)
    Productive cough 4/66 (6.1%) 3/57 (5.3%) 0/16 (0%)
    Sinus disorder 0/66 (0%) 0/57 (0%) 1/16 (6.3%)
    Sore throat 2/66 (3%) 4/57 (7%) 1/16 (6.3%)
    Skin and subcutaneous tissue disorders
    Dry skin 2/66 (3%) 3/57 (5.3%) 0/16 (0%)
    Pruritus 5/66 (7.6%) 5/57 (8.8%) 0/16 (0%)
    Rash maculo-papular 8/66 (12.1%) 7/57 (12.3%) 1/16 (6.3%)
    Skin and subcutaneous tissue disorders - Other 4/66 (6.1%) 1/57 (1.8%) 0/16 (0%)
    Vascular disorders
    Flushing 8/66 (12.1%) 4/57 (7%) 0/16 (0%)
    Hot flashes 1/66 (1.5%) 3/57 (5.3%) 0/16 (0%)
    Hypertension 16/66 (24.2%) 20/57 (35.1%) 2/16 (12.5%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title S1304 Statistician
    Organization SWOG Statistical Center
    Phone 2066674623
    Email rachaels@crab.org
    Responsible Party:
    Southwest Oncology Group
    ClinicalTrials.gov Identifier:
    NCT01903811
    Other Study ID Numbers:
    • S1304
    • NCI-2013-00796
    • PS1304_A07PAMDREVW01
    • SWOG-S1304
    • S1304
    • S1304
    • U10CA180888
    • U10CA032102
    First Posted:
    Jul 19, 2013
    Last Update Posted:
    Apr 14, 2020
    Last Verified:
    Apr 1, 2020