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Trial record 18 of 53 for:    "Adult Acute Lymphocytic Leukemia" | "Methylprednisolone hemisuccinate"

Carfilzomib and Hyper-CVAD in Treating Patients With Newly Diagnosed Acute Lymphoblastic Leukemia or Lymphoma

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ClinicalTrials.gov Identifier: NCT02293109
Recruitment Status : Recruiting
First Posted : November 18, 2014
Last Update Posted : March 2, 2018
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
University of California, Davis

Tracking Information
First Submitted Date  ICMJE November 13, 2014
First Posted Date  ICMJE November 18, 2014
Last Update Posted Date March 2, 2018
Study Start Date  ICMJE December 2015
Estimated Primary Completion Date December 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 13, 2014)
Maximum tolerated dose of carfilzomib with hyper-CVAD, defined as the dose that produces dose limiting toxicity in 17% or fewer (1/6) of patients, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4 [ Time Frame: Up to 56 days (after second course) ]
The toxicities observed at each dose level will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by NCI CTCAE version 4.0) and nadir or maximum values for the laboratory measures, time of onset (i.e. course number), duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects by dose and by course.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02293109 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 13, 2014)
  • Rate of remission [ Time Frame: Up to 56 days (after second course) ]
    All responses will be reported. Response rate among patients with measurable disease will be summarized by exact binomial confidence intervals.
  • Rate of minimal residual disease (MRD) in bone marrow aspirate samples [ Time Frame: Up to 56 days (after second course) ]
    MRD will be defined an aberrant expression of at least 2 antigens in comparison with the known patterns of antigen expression by normal maturing CD19 positive B-cells. A distinct cluster of at least 20 cells showing altered antigen expression will be characterized as an aberrant cell population.
  • Rate of MRD in bone marrow aspirate samples [ Time Frame: Up to 112 days (after 4th course) ]
    MRD will be defined an aberrant expression of at least 2 antigens in comparison with the known patterns of antigen expression by normal maturing CD19 positive B-cells. A distinct cluster of at least 20 cells showing altered antigen expression will be characterized as an aberrant cell population.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Carfilzomib and Hyper-CVAD in Treating Patients With Newly Diagnosed Acute Lymphoblastic Leukemia or Lymphoma
Official Title  ICMJE Phase I Study of Escalating Doses of Carfilzomib With Hyper-CVAD in Patients With Newly Diagnosed Acute Lymphoblastic Leukemia/Lymphoma
Brief Summary This phase I trial studies the side effects and best dose of carfilzomib when given together with the hyperfractionated (hyper)-cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone (CVAD) chemotherapy regimen in treating patients with newly diagnosed acute lymphoblastic leukemia or lymphoma. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and 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 with combination chemotherapy may kill more cancer cells.
Detailed Description

PRIMARY OBJECTIVES:

I. Safety and tolerability of administering carfilzomib in combination with hyper-CVAD chemotherapy.

II. Recommended dose of carfilzomib in combination with hyper-CVAD chemotherapy for the future phase II trial.

SECONDARY OBJECTIVES:

I. Rate of remission after 2nd and 4th cycles. II. Incidence of minimal residual disease by flow cytometry at 4th cycle.

OUTLINE: This is a dose escalation study of carfilzomib.

Patients receive carfilzomib intravenously (IV) over 30 minutes on days 0, 1, 7, and 8. Patients also receive hyper-CVAD comprising cyclophosphamide IV over 2 hours every 12 hours for 6 doses beginning on day 1, vincristine sulfate IV on days 4 and 11, doxorubicin hydrochloride IV over 2-24 hours on day 4, and dexamethasone orally (PO) on days 1-4 and 11-14 (courses 1 and 3) and methotrexate IV over 24 hours on day 1, cytarabine IV over 2 hours every 12 hours for 4 doses starting on day 2, leucovorin calcium IV or PO every 6 hours beginning 36 hours after the start of methotrexate infusion, and methylprednisolone IV every 12 hours for 6 doses beginning on day 1 (courses 2 and 4). Patients with cluster of differentiation (CD)20 positive disease also receive rituximab twice daily on days 1 and 11 of courses 1 and 3 and days 1 and 8 of courses 2 and 4. Treatment repeats every 3-4 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 28 days.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Contiguous Stage II Adult Lymphoblastic Lymphoma
  • Noncontiguous Stage II Adult Lymphoblastic Lymphoma
  • Stage I Adult Lymphoblastic Lymphoma
  • Stage III Adult Lymphoblastic Lymphoma
  • Stage IV Adult Lymphoblastic Lymphoma
  • Untreated Adult Acute Lymphoblastic Leukemia
Intervention  ICMJE
  • Drug: carfilzomib
    Given IV
    Other Names:
    • Kyprolis
    • PR-171
  • Drug: cyclophosphamide
    Given IV
    Other Names:
    • CPM
    • CTX
    • Cytoxan
    • Endoxan
    • Endoxana
  • Drug: vincristine sulfate
    Given IV
    Other Names:
    • leurocristine sulfate
    • VCR
    • Vincasar PFS
  • Drug: doxorubicin hydrochloride
    Given IV
    Other Names:
    • ADM
    • ADR
    • Adria
  • Drug: dexamethasone
    Given PO
    Other Names:
    • Aeroseb-Dex
    • Decaderm
    • Decadron
    • DM
    • DXM
  • Drug: methotrexate
    Given IV
    Other Names:
    • amethopterin
    • Folex
    • methylaminopterin
    • Mexate
    • MTX
  • Drug: cytarabine
    Given IV
    Other Names:
    • ARA-C
    • arabinofuranosylcytosine
    • arabinosylcytosine
    • Cytosar-U
    • cytosine arabinoside
  • Drug: leucovorin calcium
    Given IV or PO
    Other Names:
    • CF
    • CFR
    • LV
  • Drug: methylprednisolone
    Given IV
    Other Names:
    • Depo-Medrol
    • Medrol
    • MePRDL
    • Solu-Medrol
    • Wyacort
  • Biological: rituximab
    Other Names:
    • IDEC-C2B8
    • IDEC-C2B8 monoclonal antibody
    • Mabthera
    • MOAB IDEC-C2B8
    • Rituxan
  • Other: laboratory biomarker analysis
    Correlative studies
Study Arms  ICMJE Experimental: Treatment (carfilzomib and hyper-CVAD)
Patients receive carfilzomib IV over 30 minutes on days 0, 1, 7, and 8. Patients also receive hyper-CVAD comprising cyclophosphamide IV over 2 hours every 12 hours for 6 doses beginning on day 1, vincristine sulfate IV on days 4 and 11, doxorubicin hydrochloride IV over 2-24 hours on day 4, and dexamethasone PO on days 1-4 and 11-14 (courses 1 and 3) and methotrexate IV over 24 hours on day 1, cytarabine IV over 2 hours every 12 hours for 4 doses starting on day 2, leucovorin calcium IV or PO every 6 hours beginning 36 hours after the start of methotrexate infusion, and methylprednisolone IV every 12 hours for 6 doses beginning on day 1 (courses 2 and 4). Patients with CD20 positive disease also receive rituximab twice daily on days 1 and 11 of courses 1 and 3 and days 1 and 8 of courses 2 and 4. Treatment repeats every 3-4 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.
Interventions:
  • Drug: carfilzomib
  • Drug: cyclophosphamide
  • Drug: vincristine sulfate
  • Drug: doxorubicin hydrochloride
  • Drug: dexamethasone
  • Drug: methotrexate
  • Drug: cytarabine
  • Drug: leucovorin calcium
  • Drug: methylprednisolone
  • Biological: rituximab
  • Other: laboratory biomarker analysis
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 5, 2017)
21
Original Estimated Enrollment  ICMJE
 (submitted: November 13, 2014)
18
Estimated Study Completion Date  ICMJE December 2018
Estimated Primary Completion Date December 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Understand and voluntarily sign an informed consent form
  • Able to adhere to the study visit schedule and other protocol requirements
  • Newly diagnosed acute lymphoblastic leukemia/lymphoma
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (3 if it is directly disease related and is expected to get better if the acute lymphoblastic leukemia/lymphoma [ALL] is under control)
  • Left ventricular ejection fraction (LVEF) > 40%
  • Total bilirubin =< 3 mg/dL
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.5 x upper limit of normal
  • Creatinine clearance (CrCl) >= 45 mL/minute within 7 days prior to enrollment either measured or calculated using a standard formula (eg, Cockcroft and Gault); in cases that creatinine clearance cannot be measured accurately, 24 hour urine can be used
  • Disease free of other malignancies beside the ALL at the time of the study
  • Male subjects must agree to practice contraception
  • Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 24 hours prior to the initiation of the study and they must agree to ongoing pregnancy testing and to practice contraception

Exclusion Criteria:

  • Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form
  • Pregnant or breast feeding females
  • Active congestive heart failure (New York Heart Association [NYHA] class III to IV), symptomatic ischemia, or conduction abnormalities uncontrolled by conventional intervention
  • Unstable angina or myocardial infarction within 6 months prior to enrollment, NYHA class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or grade 3 conduction system abnormalities unless subject has a pacemaker
  • Uncontrolled hypertension, uncontrolled pulmonary hypertension or uncontrolled diabetes within 14 days prior to enrollment
  • Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to enrollment
  • Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
  • Use of any other experimental drug or therapy within 14 days of baseline
  • Known history of allergy to Captisol®
  • Known sero-positive for active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV); patients who are sero-positive because of hepatitis B virus vaccine are eligible
  • Breakpoint cluster region-Abelson positive (BCR-ABL +) patients will be excluded from the study
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 64 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02293109
Other Study ID Numbers  ICMJE 660258
UCDCC#246 ( Registry Identifier: UC Davis )
UCDCC#246 ( Other Identifier: University of California Davis )
NCI-2014-02245 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of California, Davis
Study Sponsor  ICMJE University of California, Davis
Collaborators  ICMJE Amgen
Investigators  ICMJE
Principal Investigator: Mehrdad Abedi University of California, Davis
PRS Account University of California, Davis
Verification Date March 2018

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