Carfilzomib, Rituximab, Ifosfamide, Carboplatin, and Etoposide in Treating Patients With Relapsed or Refractory Stage I-IV Diffuse Large B-cell Lymphoma

Sponsor
Roswell Park Cancer Institute (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT01959698
Collaborator
National Cancer Institute (NCI) (NIH), Amgen (Industry)
29
Enrollment
1
Location
1
Arm
133.5
Anticipated Duration (Months)
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This phase I/Ib trial studies the side effects and best dose of carfilzomib when given together with rituximab, ifosfamide, carboplatin, and etoposide and to see how well it works in treating patients with stage I-IV diffuse large B-cell lymphoma that has returned (relapsed) or that has not responded to treatment (refractory). Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, may block cancer growth in different ways by targeting certain cells. Drugs used in chemotherapy, such as ifosfamide, carboplatin, and etoposide, also 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 with rituximab, ifosfamide, carboplatin, and etoposide may be a better treatment for diffuse large B-cell lymphoma.

Detailed Description

PRIMARY OBJECTIVES:
    1. To estimate the maximum tolerated dose (MTD) and examine the dose-limiting toxicities of carfilzomib when administered in combination with rituximab, ifosfamide, carboplatin, and etoposide (C-R-ICE) in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). (Phase I)
    1. To assess the toxicity of dose regimen using the Cancer Therapy Evaluation Program (CTEP) National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE version 4.0). (Phase I)
    1. To evaluate the safety of carfilzomib (given at maximum tolerated dose [MTD] as determined in Phase I of this study) in combination with R-ICE salvage therapy in relapsed/refractory DLBCL patients. (Phase Ib)
    1. To achieve an overall response rate (complete response [CR] and partial response [PR]) of 70% after 3 cycles of C-R-ICE in patients between the ages of 18 to 75 with relapsed/refractory cluster of differentiation (CD)20-positive DLBCL previously treated with rituximab-based immunochemotherapy (e.g., rituximab, cyclophosphamide, doxorubicin, vincristine [vincristine sulfate], and prednisone [R-CHOP], rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin [REPOCH], rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, and cytarabine [R-HyperCVAD], etc.) induction. (Phase Ib)
SECONDARY OBJECTIVES:
    1. To determine the feasibility of successful mobilization of autologous stem cells (i.e., minimum of 2 x 10^6 CD34+ cells/kg should be collected) to be used for autologous stem cell transplant (ASCT)
    1. To determine toxicities associated with C-R-ICE salvage therapy
    1. To determine the time to progression (TTP), progression-free survival (PFS), and overall survival (OS) followed by ASCT; disease-free survival in CR patients.
    1. To determine the pharmacokinetics/pharmacodynamics relationship between carfilzomib's degree of proteasome inhibition and response rate along with the time course of thrombocytopenia
    1. To study differences in clinical outcomes between germinal center B-cell-like (GCB) and non-GCB relapsed/refractory DLBCL following therapy with carfilzomib and R-ICE
    1. Correlative translational research studies to include: phenotypic/genotypic analysis and functional activity (i.e., antibody-dependent cellular cytotoxicity [ADCC] and complement-mediated cytotoxicity [CMC]) of patient's peripheral blood mononuclear "effector" cells (PBMC), as well as ex vivo analysis of sensitivity of primary tumor cells to various combinations of carfilzomib versus bortezomib +/- rituximab; enzymatic assay for chymotrypsin-like activity to determine the degree of proteasome inhibition in primary DLBCL patient samples and patient PBMC specimens; explorative analysis to identify potential factors predictive of response to therapy will be performed.

OUTLINE: This is a phase I, dose-escalation study of carfilzomib, followed by a phase Ib study.

Patients receive carfilzomib intravenously (IV) over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 4 months for 1 year, every 6 months for 2 years, and then annually for 2 years.

Study Design

Study Type:
Interventional
Actual Enrollment :
29 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase I/Ib Study of Carfilzomib Plus Rituximab Plus Ifosfamide Plus Carboplatin Plus Etoposide (C-R-ICE) in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
Actual Study Start Date :
Apr 17, 2014
Actual Primary Completion Date :
Jun 1, 2020
Anticipated Study Completion Date :
Jun 1, 2025

Arms and Interventions

ArmIntervention/Treatment
Experimental: Treatment (carfilzomib, rituximab, chemotherapy)

Patients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplat
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo
  • Drug: Carfilzomib
    Given IV
    Other Names:
  • Kyprolis
  • PR-171
  • Drug: Etoposide
    Given IV
    Other Names:
  • Demethyl Epipodophyllotoxin Ethylidine Glucoside
  • EPEG
  • Lastet
  • Toposar
  • Vepesid
  • VP 16-213
  • VP-16
  • VP-16-213
  • Drug: Ifosfamide
    Given IV
    Other Names:
  • Asta Z 4942
  • Asta Z-4942
  • Cyfos
  • Holoxan
  • Holoxane
  • Ifex
  • IFO
  • IFO-Cell
  • Ifolem
  • Ifomida
  • Ifomide
  • Ifosfamidum
  • Ifoxan
  • IFX
  • Iphosphamid
  • Iphosphamide
  • Iso-Endoxan
  • Isoendoxan
  • Isophosphamide
  • Mitoxana
  • MJF 9325
  • MJF-9325
  • Naxamide
  • Seromida
  • Tronoxal
  • Z 4942
  • Z-4942
  • Other: Laboratory Biomarker Analysis
    Correlative studies

    Other: Pharmacological Study
    Correlative studies

    Biological: Rituximab
    Given IV
    Other Names:
  • ABP 798
  • BI 695500
  • C2B8 Monoclonal Antibody
  • Chimeric Anti-CD20 Antibody
  • CT-P10
  • IDEC-102
  • IDEC-C2B8
  • IDEC-C2B8 Monoclonal Antibody
  • MabThera
  • Monoclonal Antibody IDEC-C2B8
  • PF-05280586
  • Rituxan
  • Rituximab Biosimilar ABP 798
  • Rituximab Biosimilar BI 695500
  • Rituximab Biosimilar CT-P10
  • Rituximab Biosimilar PF-05280586
  • Rituximab Biosimilar RTXM83
  • Rituximab Biosimilar SAIT101
  • RTXM83
  • Outcome Measures

    Primary Outcome Measures

    1. Overall Response Rate (PR + CR) [The time measurement criteria are first met for CR until the first date that recurrent disease is objectively documented, assessed up to 12 weeks]

      Overall response rate (CR and PR) after 3 cycles of C R ICE in patients age of 18 to 75 with relapsed/refractory CD20-positive DLBCL treated with rituximab-based immunochemotherapy (e.g., R-CHOP, R-EPOCH, R-HyperCVAD, etc.) induction. Response was based on a Modified Cheson Criteria with Complete response (CR): All lesions with a longest diameter ≤ 15 mm or short axis ≤ 10 mm (Not palpable during the clinical examination, No visible nodule on imaging, And disappearance of all non-nodal target lesions Or in case of hypermetabolic disease on the baseline PET scan, negative PET scan whatever the appearance of lesions on CT) and Partial Response (PR): ≥ 50 % of sum of the products of the diameters (SPD) of target lesions or in the case of hypermetabolic lesions on the baseline PET scan, persistence of at least one PET-positive site without progression of other lesions on CT (≥ 50 % of SPD of target lesions (or longest diameter if a single nodule) No clinically enlarged liver or spleen)

    2. MTD Defined as the Dose of Carfilzomib Added to Standard R-ICE Chemotherapy Which, if Exceeded, Would Put the Patient at an Undesirable Risk of Medically Unacceptable Dose-limiting Toxicities (Phase I) [28 days]

    Secondary Outcome Measures

    1. Complete Response Rate According to the International Working Group Response Criteria as Reported by the Revised Cheson Criteria [Up to 5 years]

      Efficacy rates were estimated using simple relative frequencies. Complete response rate after 3 cycles of C R ICE in patients age of 18 to 75 with relapsed/refractory CD20-positive DLBCL treated with rituximab-based immunochemotherapy (e.g., R-CHOP, R-EPOCH, R-HyperCVAD, etc.) induction. Response was based on a Modified Cheson Criteria with Complete response (CR): All lesions with a longest diameter ≤ 15 mm or short axis ≤ 10 mm (Not palpable during the clinical examination, No visible nodule on imaging, And disappearance of all non-nodal target lesions Or in case of hypermetabolic disease on the baseline PET scan, negative PET scan whatever the appearance of lesions on CT) and Partial Response (PR): ≥ 50 % of sum of the products of the diameters (SPD) of target lesions or in the case of hypermetabolic lesions on the baseline PET scan, persistence of at least one PET-positive site without progression of other lesions on CT (≥ 50 % of SPD of target lesions (or longest diameter if a si

    2. Overall Survival [From the start of treatment until death for any reason, assessed up to 5 years]

      The estimated distributions of overall survival will be obtained using the Kaplan-Meier method. Corresponding confidence intervals using the methodology of Brookmeyer and Crowley will be computed. It is assumed a priori that any drop out times will be non-informative in terms of the censoring mechanism. Groups defined by levels of categorical or dichotomized numeric demographic/baseline variables will be compared in regards to time-to-event distributions using the log-rank test. Cox proportional hazards model regression will be utilized for multivariate analyses.

    3. Pharmacokinetics (PK)/Pharmacodynamics (PD) of Carfilzomib and Standard R-ICE Combination Therapy in Adult Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma [Pre-dose, just prior to the end of the infusion; and at 15 minutes, 30 minutes, 1, 2, 4, 6 hours post infusion on course 1, day 1, then at 24 hours post course 1 infusion on course 1, day 2 (prior to day 2 infusion)]

      A population PK/PD structural model will be developed for carfilzomib based on degree of proteasome inhibition in relation to efficacy and toxicity endpoints in the proposed study using NONMEM. This model will describe the potential relationship between carfilzomib exposure in relation to proteasome inhibition to the time course of thrombocytopenia and neutropenia as indicators of pharmacodynamics response.

    4. Progression-free Survival [Up to 5 years]

      The estimated distributions of progression-free survival will be obtained using the Kaplan-Meier method. Corresponding confidence intervals using the methodology of Brookmeyer and Crowley will be computed. It is assumed a priori that any drop out times will be non-informative in terms of the censoring mechanism. Groups defined by levels of categorical or dichotomized numeric demographic/baseline variables will be compared in regards to time-to-event distributions using the log-rank test. Cox proportional hazards model regression will be utilized for multivariate analyses.

    5. Toxicity of the Addition of Carfilzomib to R-ICE at the MTD, Assessed by the CTEP Version 4.0 of the NCI CTCAE [Up to 5 years]

      Count of participants that experienced serious adverse events assessed by the CTEP version 4.0 of the NCI CTCAE

    Other Outcome Measures

    1. Degree of Proteasome Inhibition Determined by Enzymatic Assay for Chymotrypsin-like Activity [Days 1-3 of course 1]

    2. Ex Vivo Analysis of Sensitivity of Primary Tumor Cells to Various Combinations of Carfilzomib Versus Bortezomib +/- Rituximab [Baseline]

    3. Functional Activity of Patients Peripheral Blood Mononuclear "Effector" Cells [Baseline]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Histological confirmation of relapsed/refractory CD20 positive diffuse large B-cell lymphoma

    • Ann Arbor stage I to stage IV DLBCL at the time of relapsed/refractory disease to be eligible

    • Measurable or assessable disease is required; measurable tumor size (at least one node measuring 2.25 cm^2 in bidimensional measurement) per computed tomography (CT) scan, other radiological study, and/or physical exam

    • Patients must have received at least 1 prior rituximab-based immunochemotherapy (e.g., R-CHOP, R-EPOCH, etc.)

    • = 2 weeks since major surgery

    • Patients must not have any significant toxicity associated with prior surgery, radiation therapy, chemotherapy, or immunotherapy, per principal investigator (PI) discretion

    • Life expectancy >= 3 months

    • Karnofsky score (KS) >= 50

    • Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =< 3.5 times the upper limit of normal within 14 days prior to starting therapy

    • Absolute neutrophil count (ANC) >= 1.0 x 10^9/L within 14 days prior to starting therapy*

    • Hemoglobin >= 8 g/dL (80 g/L) within 14 days prior to randomization (subjects may be receiving red blood cell [RBC] transfusions in accordance with institutional guidelines)*

    • Platelet count >= 50 x 109/L (>= 20 x 109/L if lymphoma involvement in the pretreatment bone marrow is found) within 14 days prior to starting therapy*

    • *Note: If patient has cytopenias due to bone marrow involvement, these requirements are not applicable

    • Serum creatinine of =< 1.5 mg/dL; if creatinine > 1.5 mg/dL creatinine clearance must be > 60 mL/min within 7 days prior to treatment either measured or calculated using a standard Cockcroft and Gault formula

    • Written informed consent in accordance with federal, local, and institutional guidelines

    • Females of childbearing potential (FCBP) must agree to ongoing pregnancy testing and to practice contraception; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately

    • Male subjects must agree to practice contraception

    • No known hypersensitivity to murine products

    • Patients must have normal baseline cardiac function based upon echocardiogram or gated blood pool scan (multigated acquisition scan [MUGA]) with an ejection fraction >= 50%

    • Patients who test positive for hepatitis C (HepC) antibodies (Ab) are eligible provided all of the following criteria are met: bilirubin =< 2 x upper limit of normal; ALT/AST =< 3 x upper limit of normal; and clinical evaluation to rule out cirrhosis

    • Specific guidelines will be followed regarding inclusion of relapsed/refractory DLBCL based on hepatitis B serological testing as follows:

    • Hepatitis B surface antigen (HBsAg) negative, hepatitis B core antibody (HBcAb) negative, hepatitis B surface antibody (HBsAb) positive patients are eligible

    • Patients who test positive for HBsAg are ineligible (regardless of other hepatitis B serologies)

    • Patients with HBsAg negative, but HBcAb positive (regardless of HBsAb status) should have a hepatitis B virus (HBV) deoxyribonucleic acid (DNA) testing done and protocol eligibility determined as follows:

    • If HBV DNA is positive, the subject will be excluded from the study

    • If HBV DNA is negative, the subject may be included but must undergo at least every 2 months HBV DNA polymerase chain reaction (PCR) testing from the start of treatment throughout the duration the treatment course

    Exclusion Criteria:
    • Patients with non-Hodgkin lymphoma (NHL) other than DLBCL; including "transformed" DLBCL

    • Known to be seropositive for human immunodeficiency virus (HIV); an HIV test is not required for entry on this protocol, but is required if the patient is perceived to be at risk

    • Positive serology for HBV defined as a positive test for HBsAg; in addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HepB DNA test will be performed and if positive the subject will be excluded

    • Patients with symptomatic brain involvement

    • Peripheral neuropathy of grade 2 or greater severity as defined by the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0; patients with grade 2 or higher (NCI-Common Toxicity Criteria [CTC]) neuropathy

    • Myocardial infarct within 6 months before enrollment, New York Heart Association (NYHA) class II or greater heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, clinically significant pericardial disease, or electrocardiographic evidence of acute ischemia

    • Uncontrolled intercurrent illness including, but not limited to, active infection, poorly controlled hypertension, diabetes mellitus or other serious medical or psychiatric conditions that could interfere with adherence to or completion of this study

    • Pregnant or breastfeeding

    • Patient has received other investigational drugs within 4 weeks before enrollment

    • Chemotherapy within 3 weeks of the first scheduled study treatment

    • Less than 2-years disease free from another primary malignancy (other than squamous or basal cell carcinoma of the skin, "in-situ" carcinoma of the cervix or breast, superficial bladder carcinoma, or previously treated localized prostate cancer with normal prostate-specific antigen [PSA] levels); patients are not considered to have a "currently active" malignancy if they have completed anti-cancer therapy, are considered by their physician to be at less than 30% risk of relapse and at least 2 years have lapsed

    • Major surgery, other than diagnostic surgery, within 2 weeks

    • Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib)

    • Medical condition requiring chronic use of high dose systemic corticosteroids (i.e., doses of prednisone higher than 10 mg/day or equivalent)

    • Prior high-dose chemotherapy (HDC)-ASCT

    • Active central nervous system (CNS) disease defined as symptomatic meningeal lymphoma or known CNS parenchymal lymphoma; a lumbar puncture demonstrating DLBCL at the time of registration to this study is not exclusion for study enrollment

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Roswell Park Cancer InstituteBuffaloNew YorkUnited States14263

    Sponsors and Collaborators

    • Roswell Park Cancer Institute
    • National Cancer Institute (NCI)
    • Amgen

    Investigators

    • Principal Investigator: Francisco Hernandez-ILizaliturri, Roswell Park Cancer Institute

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Roswell Park Cancer Institute
    ClinicalTrials.gov Identifier:
    NCT01959698
    Other Study ID Numbers:
    • I 240813
    • NCI-2013-01784
    • I 240813
    • P30CA016056
    • R01CA136907
    First Posted:
    Oct 10, 2013
    Last Update Posted:
    Oct 12, 2021
    Last Verified:
    Sep 1, 2021

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group TitleDose Level 1: Carfilzomib 10mg/m2 (d1-2; d8-9)Dose Level 2: Carfilzomib 15mg/m2(d1-2; d8-9)Dose Level 3: Carfilzomib 20mg/m2(d1-2; d8-9)Dose Level 4: Carfilzomib 20mg/m2(d1-2); 27mg/m2(d8-9)Dose Level 5: Carfilzomib 20mg/m2(d1-2); 36mg/m2(d8-9)Dose Level 6: Carfilzomib 20mg/m2(d1-2); 45mg/m2(d8-9)Expansion Cohort: Carfilzomib 20mg/m2(d1-2); 45mg/m2(d8-9)
    Arm/Group DescriptionPatients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Carfilzomib: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Rituximab: Given IVPatients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.Patients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.Patients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.Patients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.Patients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.Patients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
    Period Title: Overall Study
    STARTED3333368
    COMPLETED2321334
    NOT COMPLETED1012034

    Baseline Characteristics

    Arm/Group TitleDose Level 1: Carfilzomib 10mg/m2(d1-2; d8-9)(Carfilzomib, Rituximab, Chemotherapy)Dose Level 2: Carfilzomib 15mg/m2(d1-2; d8-9)Dose Level 3: Carfilzomib 20mg/m2(d1-2; d8-9)Dose Level 4: Carfilzomib 20mg/m2(d1-2); 27mg/m2(d8-9)Dose Level 5: Carfilzomib 20mg/m2(d1-2); 36mg/m2(d8-9)Dose Level 6: Carfilzomib 20mg/m2(d1-2); 45mg/m2(d8-9)Expansion Cohort: Carfilzomib 20mg/m2(d1-2); 45mg/m2(d8-9)Total
    Arm/Group DescriptionPatients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Carfilzomib: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Rituximab: Given IVPatients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Carfilzomib: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Rituximab: Given IVPatients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Carfilzomib: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Rituximab: Given IVPatients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Carfilzomib: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Rituximab: Given IVPatients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Carfilzomib: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Rituximab: Given IVPatients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Carfilzomib: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Rituximab: Given IVPatients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Carfilzomib: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Rituximab: Given IVTotal of all reporting groups
    Overall Participants333336829
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    1
    33.3%
    2
    66.7%
    2
    66.7%
    2
    66.7%
    3
    100%
    4
    66.7%
    6
    75%
    20
    69%
    >=65 years
    2
    66.7%
    1
    33.3%
    1
    33.3%
    1
    33.3%
    0
    0%
    2
    33.3%
    2
    25%
    9
    31%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    65.6
    (11.2)
    62.5
    (4.4)
    64.6
    (8.6)
    45.5
    (21.3)
    58.9
    (1.7)
    63.3
    (4.3)
    59.1
    (11.8)
    60.2
    (10.9)
    Sex: Female, Male (Count of Participants)
    Female
    2
    66.7%
    0
    0%
    1
    33.3%
    0
    0%
    0
    0%
    3
    50%
    5
    62.5%
    11
    37.9%
    Male
    1
    33.3%
    3
    100%
    2
    66.7%
    3
    100%
    3
    100%
    3
    50%
    3
    37.5%
    18
    62.1%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    White
    3
    100%
    3
    100%
    3
    100%
    3
    100%
    3
    100%
    6
    100%
    8
    100%
    29
    100%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%

    Outcome Measures

    1. Primary Outcome
    TitleOverall Response Rate (PR + CR)
    DescriptionOverall response rate (CR and PR) after 3 cycles of C R ICE in patients age of 18 to 75 with relapsed/refractory CD20-positive DLBCL treated with rituximab-based immunochemotherapy (e.g., R-CHOP, R-EPOCH, R-HyperCVAD, etc.) induction. Response was based on a Modified Cheson Criteria with Complete response (CR): All lesions with a longest diameter ≤ 15 mm or short axis ≤ 10 mm (Not palpable during the clinical examination, No visible nodule on imaging, And disappearance of all non-nodal target lesions Or in case of hypermetabolic disease on the baseline PET scan, negative PET scan whatever the appearance of lesions on CT) and Partial Response (PR): ≥ 50 % of sum of the products of the diameters (SPD) of target lesions or in the case of hypermetabolic lesions on the baseline PET scan, persistence of at least one PET-positive site without progression of other lesions on CT (≥ 50 % of SPD of target lesions (or longest diameter if a single nodule) No clinically enlarged liver or spleen)
    Time FrameThe time measurement criteria are first met for CR until the first date that recurrent disease is objectively documented, assessed up to 12 weeks

    Outcome Measure Data

    Analysis Population Description
    All treated and eligible patients. Per the protocol "The efficacy analysis will include evaluable patients in Phase I and Phase Ib portions combined".
    Arm/Group TitleTreatment (Carfilzomib, Rituximab, Chemotherapy)
    Arm/Group DescriptionPatients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Carfilzomib: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Rituximab: Given IV
    Measure Participants29
    Number (95% Confidence Interval) [percentage of participants]
    66
    2200%
    2. Primary Outcome
    TitleMTD Defined as the Dose of Carfilzomib Added to Standard R-ICE Chemotherapy Which, if Exceeded, Would Put the Patient at an Undesirable Risk of Medically Unacceptable Dose-limiting Toxicities (Phase I)
    Description
    Time Frame28 days

    Outcome Measure Data

    Analysis Population Description
    All treated and eligible patients
    Arm/Group TitleDose Level 1: Carfilzomib 10mg/m2(d1-2; d8-9)Dose Level 2: Carfilzomib 15mg/m2(d1-2; d8-9)Dose Level 3: Carfilzomib 20mg/m2(d1-2; d8-9)Dose Level 4: Carfilzomib 20mg/m2(d1-2); 27mg/m2(d8-9)Dose Level 5: Carfilzomib 20mg/m2(d1-2); 36mg/m2(d8-9)Dose Level 6: Carfilzomib 20mg/m2(d1-2); 45mg/m2(d8-9)Expansion Cohort: Carfilzomib 20mg/m2(d1-2); 45mg/m2(d8-9)
    Arm/Group DescriptionPatients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Carfilzomib: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Rituximab: Given IVPatients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.Patients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.Patients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.Patients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.Patients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.Patients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
    Measure Participants3333368
    Number [mg/m2]
    NA
    NA
    NA
    NA
    NA
    NA
    NA
    3. Secondary Outcome
    TitleComplete Response Rate According to the International Working Group Response Criteria as Reported by the Revised Cheson Criteria
    DescriptionEfficacy rates were estimated using simple relative frequencies. Complete response rate after 3 cycles of C R ICE in patients age of 18 to 75 with relapsed/refractory CD20-positive DLBCL treated with rituximab-based immunochemotherapy (e.g., R-CHOP, R-EPOCH, R-HyperCVAD, etc.) induction. Response was based on a Modified Cheson Criteria with Complete response (CR): All lesions with a longest diameter ≤ 15 mm or short axis ≤ 10 mm (Not palpable during the clinical examination, No visible nodule on imaging, And disappearance of all non-nodal target lesions Or in case of hypermetabolic disease on the baseline PET scan, negative PET scan whatever the appearance of lesions on CT) and Partial Response (PR): ≥ 50 % of sum of the products of the diameters (SPD) of target lesions or in the case of hypermetabolic lesions on the baseline PET scan, persistence of at least one PET-positive site without progression of other lesions on CT (≥ 50 % of SPD of target lesions (or longest diameter if a si
    Time FrameUp to 5 years

    Outcome Measure Data

    Analysis Population Description
    All treated and eligible patients, Per the protocol "The efficacy analysis will include evaluable patients in Phase I and Phase Ib portions combined".
    Arm/Group TitleTreatment (Carfilzomib, Rituximab, Chemotherapy)
    Arm/Group DescriptionPatients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Carfilzomib: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Rituximab: Given IV
    Measure Participants29
    Number (95% Confidence Interval) [percentage of participants]
    48
    1600%
    4. Secondary Outcome
    TitleOverall Survival
    DescriptionThe estimated distributions of overall survival will be obtained using the Kaplan-Meier method. Corresponding confidence intervals using the methodology of Brookmeyer and Crowley will be computed. It is assumed a priori that any drop out times will be non-informative in terms of the censoring mechanism. Groups defined by levels of categorical or dichotomized numeric demographic/baseline variables will be compared in regards to time-to-event distributions using the log-rank test. Cox proportional hazards model regression will be utilized for multivariate analyses.
    Time FrameFrom the start of treatment until death for any reason, assessed up to 5 years

    Outcome Measure Data

    Analysis Population Description
    All treated and eligible patients, Per the protocol "The efficacy analysis will include evaluable patients in Phase I and Phase Ib portions combined".
    Arm/Group TitleTreatment (Carfilzomib, Rituximab, Chemotherapy)
    Arm/Group DescriptionPatients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Carfilzomib: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Rituximab: Given IV
    Measure Participants29
    Median (95% Confidence Interval) [months]
    22.6
    5. Secondary Outcome
    TitlePharmacokinetics (PK)/Pharmacodynamics (PD) of Carfilzomib and Standard R-ICE Combination Therapy in Adult Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma
    DescriptionA population PK/PD structural model will be developed for carfilzomib based on degree of proteasome inhibition in relation to efficacy and toxicity endpoints in the proposed study using NONMEM. This model will describe the potential relationship between carfilzomib exposure in relation to proteasome inhibition to the time course of thrombocytopenia and neutropenia as indicators of pharmacodynamics response.
    Time FramePre-dose, just prior to the end of the infusion; and at 15 minutes, 30 minutes, 1, 2, 4, 6 hours post infusion on course 1, day 1, then at 24 hours post course 1 infusion on course 1, day 2 (prior to day 2 infusion)

    Outcome Measure Data

    Analysis Population Description
    The analysis of this endpoint was contingent on ancillary grant funding, which did not occur. Hence these endpoints were not collected.
    Arm/Group TitleTreatment (Carfilzomib, Rituximab, Chemotherapy)
    Arm/Group DescriptionPatients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Carfilzomib: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Rituximab: Given IV
    Measure Participants0
    6. Secondary Outcome
    TitleProgression-free Survival
    DescriptionThe estimated distributions of progression-free survival will be obtained using the Kaplan-Meier method. Corresponding confidence intervals using the methodology of Brookmeyer and Crowley will be computed. It is assumed a priori that any drop out times will be non-informative in terms of the censoring mechanism. Groups defined by levels of categorical or dichotomized numeric demographic/baseline variables will be compared in regards to time-to-event distributions using the log-rank test. Cox proportional hazards model regression will be utilized for multivariate analyses.
    Time FrameUp to 5 years

    Outcome Measure Data

    Analysis Population Description
    All treated and eligible patients, Per the protocol "The efficacy analysis will include evaluable patients in Phase I and Phase Ib portions combined".
    Arm/Group TitleTreatment (Carfilzomib, Rituximab, Chemotherapy)
    Arm/Group DescriptionPatients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Carfilzomib: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Rituximab: Given IV
    Measure Participants29
    Median (95% Confidence Interval) [months]
    15.2
    7. Secondary Outcome
    TitleToxicity of the Addition of Carfilzomib to R-ICE at the MTD, Assessed by the CTEP Version 4.0 of the NCI CTCAE
    DescriptionCount of participants that experienced serious adverse events assessed by the CTEP version 4.0 of the NCI CTCAE
    Time FrameUp to 5 years

    Outcome Measure Data

    Analysis Population Description
    All treated and eligible patients
    Arm/Group TitleDose Level 1: Carfilzomib 10mg/m2(d1-2; d8-9)Dose Level 2: Carfilzomib 15mg/m2(d1-2; d8-9)Dose Level 3: Carfilzomib 20mg/m2(d1-2; d8-9)Dose Level 4: Carfilzomib 20mg/m2(d1-2); 27mg/m2(d8-9)Dose Level 5: Carfilzomib 20mg/m2(d1-2); 36mg/m2(d8-9)Dose Level 6: Carfilzomib 20mg/m2(d1-2); 45mg/m2(d8-9)Expansion Cohort: Carfilzomib 20mg/m2(d1-2); 45mg/m2(d8-9)
    Arm/Group DescriptionPatients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Carfilzomib: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Rituximab: Given IVPatients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.Patients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.Patients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.Patients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.Patients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.Patients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
    Measure Participants3333368
    Count of Participants [Participants]
    2
    66.7%
    0
    0%
    0
    0%
    1
    33.3%
    1
    33.3%
    3
    50%
    4
    50%
    8. Other Pre-specified Outcome
    TitleDegree of Proteasome Inhibition Determined by Enzymatic Assay for Chymotrypsin-like Activity
    Description
    Time FrameDays 1-3 of course 1

    Outcome Measure Data

    Analysis Population Description
    The analysis of this endpoint was contingent on ancillary grant funding, which did not occur. Hence these endpoints were not collected.
    Arm/Group TitleTreatment (Carfilzomib, Rituximab, Chemotherapy)
    Arm/Group DescriptionPatients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Carfilzomib: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Rituximab: Given IV
    Measure Participants0
    9. Other Pre-specified Outcome
    TitleEx Vivo Analysis of Sensitivity of Primary Tumor Cells to Various Combinations of Carfilzomib Versus Bortezomib +/- Rituximab
    Description
    Time FrameBaseline

    Outcome Measure Data

    Analysis Population Description
    The analysis of this endpoint was contingent on ancillary grant funding, which did not occur. Hence these endpoints were not collected.
    Arm/Group TitleTreatment (Carfilzomib, Rituximab, Chemotherapy)
    Arm/Group DescriptionPatients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Carfilzomib: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Rituximab: Given IV
    Measure Participants0
    10. Other Pre-specified Outcome
    TitleFunctional Activity of Patients Peripheral Blood Mononuclear "Effector" Cells
    Description
    Time FrameBaseline

    Outcome Measure Data

    Analysis Population Description
    The analysis of this endpoint was contingent on ancillary grant funding, which did not occur. Hence these endpoints were not collected.
    Arm/Group TitleTreatment (Carfilzomib, Rituximab, Chemotherapy)
    Arm/Group DescriptionPatients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Carfilzomib: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Rituximab: Given IV
    Measure Participants0

    Adverse Events

    Time FrameBaseline, weekly until 30 days after the last intervention or until the event has resolved, stabilized, death, or a new treatment is started, whichever comes first, will be reported.
    Adverse Event Reporting Description Assess the toxicity of dose regimen using the CTEP NCI Common Terminology Criteria for Adverse Events (CTCAE Version 4.0).
    Arm/Group TitleDose Level 1: Carfilzomib 10mg/m2(d1-2; d8-9)Dose Level 2: Carfilzomib 15mg/m2(d1-2; d8-9)Dose Level 3: Carfilzomib 20mg/m2(d1-2; d8-9)Dose Level 4: Carfilzomib 20mg/m2(d1-2); 27mg/m2(d8-9)Dose Level 5: Carfilzomib 20mg/m2(d1-2); 36mg/m2(d8-9)Dose Level 6: Carfilzomib 20mg/m2(d1-2); 45mg/m2(d8-9)Expansion Cohort: Carfilzomib 20mg/m2(d1-2); 45mg/m2(d8-9)
    Arm/Group DescriptionPatients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Carfilzomib: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Rituximab: Given IVPatients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Carfilzomib: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Rituximab: Given IVPatients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Carfilzomib: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Rituximab: Given IVPatients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Carfilzomib: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Rituximab: Given IVPatients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Carfilzomib: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Rituximab: Given IVPatients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Carfilzomib: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Rituximab: Given IVPatients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Carfilzomib: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Rituximab: Given IV
    All Cause Mortality
    Dose Level 1: Carfilzomib 10mg/m2(d1-2; d8-9)Dose Level 2: Carfilzomib 15mg/m2(d1-2; d8-9)Dose Level 3: Carfilzomib 20mg/m2(d1-2; d8-9)Dose Level 4: Carfilzomib 20mg/m2(d1-2); 27mg/m2(d8-9)Dose Level 5: Carfilzomib 20mg/m2(d1-2); 36mg/m2(d8-9)Dose Level 6: Carfilzomib 20mg/m2(d1-2); 45mg/m2(d8-9)Expansion Cohort: Carfilzomib 20mg/m2(d1-2); 45mg/m2(d8-9)
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total3/3 (100%) 0/3 (0%) 1/3 (33.3%) 3/3 (100%) 1/3 (33.3%) 4/6 (66.7%) 2/8 (25%)
    Serious Adverse Events
    Dose Level 1: Carfilzomib 10mg/m2(d1-2; d8-9)Dose Level 2: Carfilzomib 15mg/m2(d1-2; d8-9)Dose Level 3: Carfilzomib 20mg/m2(d1-2; d8-9)Dose Level 4: Carfilzomib 20mg/m2(d1-2); 27mg/m2(d8-9)Dose Level 5: Carfilzomib 20mg/m2(d1-2); 36mg/m2(d8-9)Dose Level 6: Carfilzomib 20mg/m2(d1-2); 45mg/m2(d8-9)Expansion Cohort: Carfilzomib 20mg/m2(d1-2); 45mg/m2(d8-9)
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total2/3 (66.7%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 1/3 (33.3%) 3/6 (50%) 4/8 (50%)
    Blood and lymphatic system disorders
    Anaemia0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 01/8 (12.5%) 6
    Febrile neutropenia1/3 (33.3%) 30/3 (0%) 00/3 (0%) 01/3 (33.3%) 30/3 (0%) 00/6 (0%) 01/8 (12.5%) 3
    Gastrointestinal disorders
    Abdominal pain0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 01/6 (16.7%) 30/8 (0%) 0
    Gastric haemorrhage1/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Obstruction gastric0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 01/6 (16.7%) 30/8 (0%) 0
    General disorders
    Pain0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 01/6 (16.7%) 30/8 (0%) 0
    Pyrexia0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 01/8 (12.5%) 3
    Infections and infestations
    Lymph node abscess1/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Pneumonia0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 01/6 (16.7%) 30/8 (0%) 0
    Sepsis0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 01/8 (12.5%) 3
    Soft tissue infection0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 01/6 (16.7%) 30/8 (0%) 0
    Investigations
    Platelet count decreased0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 01/8 (12.5%) 6
    Metabolism and nutrition disorders
    Dehydration0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 01/3 (33.3%) 30/6 (0%) 00/8 (0%) 0
    Musculoskeletal and connective tissue disorders
    Back pain0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 01/8 (12.5%) 3
    Psychiatric disorders
    Confusional state0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 02/8 (25%) 6
    Psychotic disorder0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 01/6 (16.7%) 30/8 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Hypoxia0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 01/8 (12.5%) 3
    Other (Not Including Serious) Adverse Events
    Dose Level 1: Carfilzomib 10mg/m2(d1-2; d8-9)Dose Level 2: Carfilzomib 15mg/m2(d1-2; d8-9)Dose Level 3: Carfilzomib 20mg/m2(d1-2; d8-9)Dose Level 4: Carfilzomib 20mg/m2(d1-2); 27mg/m2(d8-9)Dose Level 5: Carfilzomib 20mg/m2(d1-2); 36mg/m2(d8-9)Dose Level 6: Carfilzomib 20mg/m2(d1-2); 45mg/m2(d8-9)Expansion Cohort: Carfilzomib 20mg/m2(d1-2); 45mg/m2(d8-9)
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total3/3 (100%) 3/3 (100%) 3/3 (100%) 3/3 (100%) 3/3 (100%) 6/6 (100%) 8/8 (100%)
    Blood and lymphatic system disorders
    Anaemia2/3 (66.7%) 303/3 (100%) 271/3 (33.3%) 32/3 (66.7%) 92/3 (66.7%) 64/6 (66.7%) 151/8 (12.5%) 3
    Disseminated intravascular coagulation1/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Cardiac disorders
    Cardiac failure congestive1/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Palpitations0/3 (0%) 00/3 (0%) 00/3 (0%) 01/3 (33.3%) 30/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Sinus bradycardia1/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Sinus tachycardia1/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Eye disorders
    Eye disorder0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 01/6 (16.7%) 30/8 (0%) 0
    Vision blurred1/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 01/3 (33.3%) 32/6 (33.3%) 61/8 (12.5%) 3
    Gastrointestinal disorders
    Abdominal pain1/3 (33.3%) 30/3 (0%) 00/3 (0%) 01/3 (33.3%) 30/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Aphthous ulcer1/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Constipation0/3 (0%) 02/3 (66.7%) 91/3 (33.3%) 31/3 (33.3%) 32/3 (66.7%) 64/6 (66.7%) 184/8 (50%) 12
    Diarrhoea1/3 (33.3%) 92/3 (66.7%) 62/3 (66.7%) 62/3 (66.7%) 61/3 (33.3%) 32/6 (33.3%) 92/8 (25%) 6
    Dry mouth1/3 (33.3%) 30/3 (0%) 01/3 (33.3%) 60/3 (0%) 00/3 (0%) 01/6 (16.7%) 31/8 (12.5%) 3
    Dyspepsia0/3 (0%) 01/3 (33.3%) 30/3 (0%) 00/3 (0%) 02/3 (66.7%) 62/6 (33.3%) 90/8 (0%) 0
    Dysphagia1/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 01/3 (33.3%) 30/6 (0%) 00/8 (0%) 0
    Eructation0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 01/6 (16.7%) 30/8 (0%) 0
    Flatulence0/3 (0%) 01/3 (33.3%) 30/3 (0%) 01/3 (33.3%) 30/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Gingival pain0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 01/6 (16.7%) 30/8 (0%) 0
    Haemorrhoids1/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 01/6 (16.7%) 30/8 (0%) 0
    Mouth ulceration0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 01/8 (12.5%) 3
    Nausea2/3 (66.7%) 63/3 (100%) 183/3 (100%) 122/3 (66.7%) 92/3 (66.7%) 64/6 (66.7%) 154/8 (50%) 15
    Oral pain0/3 (0%) 00/3 (0%) 01/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Proctalgia0/3 (0%) 00/3 (0%) 00/3 (0%) 01/3 (33.3%) 30/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Rectal haemorrhage0/3 (0%) 01/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Stomatitis1/3 (33.3%) 30/3 (0%) 01/3 (33.3%) 31/3 (33.3%) 31/3 (33.3%) 30/6 (0%) 00/8 (0%) 0
    Toothache0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 01/8 (12.5%) 3
    Vomiting3/3 (100%) 93/3 (100%) 90/3 (0%) 01/3 (33.3%) 31/3 (33.3%) 32/6 (33.3%) 60/8 (0%) 0
    General disorders
    Asthenia3/3 (100%) 91/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Chills2/3 (66.7%) 60/3 (0%) 01/3 (33.3%) 30/3 (0%) 00/3 (0%) 01/6 (16.7%) 31/8 (12.5%) 3
    Extravasation0/3 (0%) 01/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Fatigue3/3 (100%) 120/3 (0%) 02/3 (66.7%) 63/3 (100%) 93/3 (100%) 92/6 (33.3%) 63/8 (37.5%) 9
    Infusion site erythema1/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 01/8 (12.5%) 3
    Non-cardiac chest pain0/3 (0%) 00/3 (0%) 01/3 (33.3%) 31/3 (33.3%) 60/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Oedema0/3 (0%) 01/3 (33.3%) 31/3 (33.3%) 30/3 (0%) 01/3 (33.3%) 32/6 (33.3%) 61/8 (12.5%) 3
    Oedema peripheral0/3 (0%) 01/3 (33.3%) 30/3 (0%) 02/3 (66.7%) 60/3 (0%) 01/6 (16.7%) 30/8 (0%) 0
    Pain0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 01/3 (33.3%) 30/6 (0%) 00/8 (0%) 0
    Pyrexia1/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 02/8 (25%) 6
    Immune system disorders
    Hypersensitivity0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 01/8 (12.5%) 3
    Infections and infestations
    Candida infection0/3 (0%) 00/3 (0%) 01/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Device related infection1/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Infection0/3 (0%) 00/3 (0%) 00/3 (0%) 01/3 (33.3%) 30/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Lip infection0/3 (0%) 00/3 (0%) 01/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Rhinovirus infection0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 01/8 (12.5%) 3
    Upper respiratory tract infection0/3 (0%) 00/3 (0%) 00/3 (0%) 01/3 (33.3%) 30/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Wound infection1/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Injury, poisoning and procedural complications
    Contusion0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 01/6 (16.7%) 30/8 (0%) 0
    Infusion related reaction1/3 (33.3%) 31/3 (33.3%) 31/3 (33.3%) 31/3 (33.3%) 30/3 (0%) 01/6 (16.7%) 32/8 (25%) 6
    Scar0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 01/3 (33.3%) 30/6 (0%) 00/8 (0%) 0
    Wound0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 01/6 (16.7%) 30/8 (0%) 0
    Investigations
    Alanine aminotransferase increased0/3 (0%) 01/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Aspartate aminotransferase increased0/3 (0%) 01/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Blood lactic acid increased0/3 (0%) 00/3 (0%) 01/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Lymphocyte count decreased0/3 (0%) 01/3 (33.3%) 120/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Neutrophil count decreased3/3 (100%) 213/3 (100%) 240/3 (0%) 00/3 (0%) 00/3 (0%) 01/6 (16.7%) 62/8 (25%) 6
    Platelet count decreased3/3 (100%) 243/3 (100%) 211/3 (33.3%) 33/3 (100%) 212/3 (66.7%) 65/6 (83.3%) 184/8 (50%) 15
    Prothrombin time prolonged1/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Troponin increased1/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Weight decreased1/3 (33.3%) 30/3 (0%) 01/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Weight increased1/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    White blood cell count decreased1/3 (33.3%) 92/3 (66.7%) 211/3 (33.3%) 30/3 (0%) 00/3 (0%) 01/6 (16.7%) 60/8 (0%) 0
    Metabolism and nutrition disorders
    Decreased appetite1/3 (33.3%) 60/3 (0%) 02/3 (66.7%) 62/3 (66.7%) 61/3 (33.3%) 32/6 (33.3%) 92/8 (25%) 6
    Dehydration1/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 02/3 (66.7%) 60/6 (0%) 00/8 (0%) 0
    Fluid overload0/3 (0%) 01/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Gout0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 01/8 (12.5%) 3
    Hyperglycaemia0/3 (0%) 02/3 (66.7%) 90/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 01/8 (12.5%) 3
    Hyperkalaemia1/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Hypocalcaemia1/3 (33.3%) 31/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Hypochloraemia0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 01/6 (16.7%) 30/8 (0%) 0
    Hypoglycaemia0/3 (0%) 01/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Hypokalaemia2/3 (66.7%) 240/3 (0%) 00/3 (0%) 01/3 (33.3%) 30/3 (0%) 00/6 (0%) 02/8 (25%) 6
    Hypomagnesaemia1/3 (33.3%) 90/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Hyponatraemia0/3 (0%) 01/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 01/6 (16.7%) 60/8 (0%) 0
    Hypophosphataemia1/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 01/8 (12.5%) 6
    Musculoskeletal and connective tissue disorders
    Arthralgia0/3 (0%) 00/3 (0%) 01/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Back pain0/3 (0%) 00/3 (0%) 00/3 (0%) 01/3 (33.3%) 30/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Bone pain0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 01/6 (16.7%) 31/8 (12.5%) 3
    Muscle spasms0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 01/3 (33.3%) 30/6 (0%) 00/8 (0%) 0
    Muscular weakness0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 01/3 (33.3%) 32/6 (33.3%) 62/8 (25%) 6
    Musculoskeletal pain0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 01/6 (16.7%) 30/8 (0%) 0
    Myalgia0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 01/6 (16.7%) 30/8 (0%) 0
    Neck pain1/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Pain in extremity0/3 (0%) 01/3 (33.3%) 31/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Nervous system disorders
    Cognitive disorder0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 01/6 (16.7%) 30/8 (0%) 0
    Dizziness2/3 (66.7%) 62/3 (66.7%) 60/3 (0%) 01/3 (33.3%) 31/3 (33.3%) 31/6 (16.7%) 30/8 (0%) 0
    Dysgeusia0/3 (0%) 00/3 (0%) 03/3 (100%) 91/3 (33.3%) 32/3 (66.7%) 60/6 (0%) 01/8 (12.5%) 3
    Headache0/3 (0%) 01/3 (33.3%) 31/3 (33.3%) 32/3 (66.7%) 62/3 (66.7%) 60/6 (0%) 02/8 (25%) 6
    Peripheral sensory neuropathy1/3 (33.3%) 60/3 (0%) 02/3 (66.7%) 91/3 (33.3%) 31/3 (33.3%) 30/6 (0%) 00/8 (0%) 0
    Taste disorder1/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Tremor0/3 (0%) 00/3 (0%) 01/3 (33.3%) 30/3 (0%) 00/3 (0%) 02/6 (33.3%) 120/8 (0%) 0
    Psychiatric disorders
    Anxiety0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 01/3 (33.3%) 30/6 (0%) 00/8 (0%) 0
    Confusional state0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 01/8 (12.5%) 3
    Hallucination0/3 (0%) 00/3 (0%) 01/3 (33.3%) 60/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Insomnia1/3 (33.3%) 31/3 (33.3%) 31/3 (33.3%) 30/3 (0%) 01/3 (33.3%) 30/6 (0%) 00/8 (0%) 0
    Mental disorder0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 01/6 (16.7%) 30/8 (0%) 0
    Renal and urinary disorders
    Dysuria0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 01/3 (33.3%) 30/6 (0%) 00/8 (0%) 0
    Haematuria0/3 (0%) 00/3 (0%) 00/3 (0%) 01/3 (33.3%) 30/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Pollakiuria1/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Cough0/3 (0%) 00/3 (0%) 02/3 (66.7%) 62/3 (66.7%) 61/3 (33.3%) 32/6 (33.3%) 60/8 (0%) 0
    Dysphonia1/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 01/3 (33.3%) 30/6 (0%) 00/8 (0%) 0
    Dyspnoea0/3 (0%) 00/3 (0%) 01/3 (33.3%) 62/3 (66.7%) 91/3 (33.3%) 30/6 (0%) 00/8 (0%) 0
    Dyspnoea exertional1/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Epistaxis0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 01/3 (33.3%) 30/6 (0%) 03/8 (37.5%) 9
    Hiccups0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 01/3 (33.3%) 30/6 (0%) 00/8 (0%) 0
    Nasal congestion0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 01/3 (33.3%) 30/6 (0%) 00/8 (0%) 0
    Oropharyngeal pain0/3 (0%) 00/3 (0%) 01/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/6 (0%) 01/8 (12.5%) 3
    Pneumonitis1/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Productive cough0/3 (0%) 00/3 (0%) 00/3 (0%) 01/3 (33.3%) 30/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Pulmonary embolism0/3 (0%) 01/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Rhinitis allergic0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 01/6 (16.7%) 30/8 (0%) 0
    Upper-airway cough syndrome1/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Skin and subcutaneous tissue disorders
    Alopecia2/3 (66.7%) 90/3 (0%) 02/3 (66.7%) 60/3 (0%) 01/3 (33.3%) 34/6 (66.7%) 124/8 (50%) 12
    Dry skin1/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Ecchymosis1/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Erythema0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 01/6 (16.7%) 30/8 (0%) 0
    Generalised erythema1/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Hyperhidrosis0/3 (0%) 00/3 (0%) 00/3 (0%) 01/3 (33.3%) 30/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Nail disorder1/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Nail ridging0/3 (0%) 00/3 (0%) 01/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Night sweats0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 01/8 (12.5%) 3
    Onychoclasis0/3 (0%) 00/3 (0%) 00/3 (0%) 01/3 (33.3%) 30/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Onychomadesis0/3 (0%) 00/3 (0%) 01/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Pain of skin0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 01/8 (12.5%) 3
    Scab0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 01/6 (16.7%) 30/8 (0%) 0
    Skin induration0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 01/6 (16.7%) 30/8 (0%) 0
    Vascular disorders
    Deep vein thrombosis0/3 (0%) 01/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 00/8 (0%) 0
    Hot flush0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 01/6 (16.7%) 30/8 (0%) 0
    Hypertension0/3 (0%) 01/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 01/6 (16.7%) 60/8 (0%) 0
    Hypotension1/3 (33.3%) 31/3 (33.3%) 30/3 (0%) 00/3 (0%) 00/3 (0%) 00/6 (0%) 03/8 (37.5%) 9
    Orthostatic hypotension0/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 00/3 (0%) 01/6 (16.7%) 30/8 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/TitleSenior Administrator, Compliance - Clinical Research Services
    OrganizationRoswell Park Comprehensive Cancer Center
    Phone716-845-2300
    EmailAdrienne.Groman@RoswellPark.org
    Responsible Party:
    Roswell Park Cancer Institute
    ClinicalTrials.gov Identifier:
    NCT01959698
    Other Study ID Numbers:
    • I 240813
    • NCI-2013-01784
    • I 240813
    • P30CA016056
    • R01CA136907
    First Posted:
    Oct 10, 2013
    Last Update Posted:
    Oct 12, 2021
    Last Verified:
    Sep 1, 2021