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Trial record 34 of 183 for:    carfilzomib OR pr-171

Carfilzomib in Treating Patients With Multiple Myeloma in First Relapse or Refractory to First-Line Therapy

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ClinicalTrials.gov Identifier: NCT02020941
Recruitment Status : Terminated (Slow accrual)
First Posted : December 25, 2013
Results First Posted : November 2, 2016
Last Update Posted : November 2, 2016
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Attaya Suvannasankha, Indiana University School of Medicine

Tracking Information
First Submitted Date  ICMJE December 19, 2013
First Posted Date  ICMJE December 25, 2013
Results First Submitted Date  ICMJE September 14, 2016
Results First Posted Date  ICMJE November 2, 2016
Last Update Posted Date November 2, 2016
Study Start Date  ICMJE September 2013
Actual Primary Completion Date January 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 14, 2016)
Overall Response Rate (ORR) After 8 Courses of Treatment [ Time Frame: At 32 weeks ]
: Evaluate the overall response rate of patients receiving therapy. Patients are considered as having a response if their overall response is Partial Response or better. The percentage of patients achieving this and the exact 95% confidence interval will be calculated. Responses will be defined using the International Myeloma Working Group-Uniform Response Criteria (IMWG-URC).
Original Primary Outcome Measures  ICMJE
 (submitted: December 19, 2013)
Overall response rate (ORR) after 8 courses of treatment, defined as the proportion of patients with the best overall response of PR or better [ Time Frame: At 32 weeks ]
ORR, together with corresponding 95% exact binomial confidence interval, will be calculated. Responses will be defined using the International Myeloma Working Group-Uniform Response Criteria (IMWG-URC).
Change History Complete list of historical versions of study NCT02020941 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 14, 2016)
  • Overall Response Rate (ORR) After 4 Courses of Treatment [ Time Frame: At 16 weeks ]
    Evaluate the overall response rate of patients receiving therapy. Patients are considered as having a response if their overall response is Partial Response or better. The percentage of patients achieving this and the exact 95% confidence interval will be calculated. Responses will be defined using the International Myeloma Working Group-Uniform Response Criteria (IMWG-URC).
  • Progression-free Survival (PFS) [ Time Frame: Time from first dose to first observed disease progression or death, assessed up to 2 years ]
    Analysis will be performed using Kaplan-Meier estimates. Time from date on treatment to date of progression for patients who progressed or date of death for patients who died without progressing. The observations of patients remaining alive and progression free were censored at date of last disease evaluation.
  • Time to Progression (TTP) [ Time Frame: Time from first dose to disease progression, assessed up to 2 years ]
    Analysis will be performed using Kaplan-Meier estimates. Time from date on treatment to date of progression. The observations of patients who died or remained alive and progression free were censored at date of death or last disease evaluation, respectively.
  • Duration of Response (DOR) [ Time Frame: Time from first evidence of PR or better to disease progression or death, assessed up to 2 years ]
    Analysis will be performed using Kaplan-Meier estimates. Time from date of first confirmed response of partial response or better to date of progression or death. Only patients who had a response of partial response or better will be included in this analysis.
  • Treatment Related Adverse Events Grade 3 or Higher [ Time Frame: Up to 30 days after completion of study treatment, up to 2 years ]
    Number of unique patients who had a treatment related (possible, probable or definite) adverse events that were graded 3 or greater.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 19, 2013)
  • ORR at 4 courses [ Time Frame: At 16 weeks ]
    ORR, together with corresponding 95% exact binomial confidence interval, will be calculated. Responses will be defined using the IMWG-URC.
  • Progression-free Survival (PFS) [ Time Frame: Time from first dose to first observed disease progression or death, assessed up to 2 years ]
    Analysis will be performed using the Kaplan-Meier method. Medians and other quartiles for each endpoint will be estimated in addition to the corresponding two-sided 95% confidence intervals.
  • Time to Progression (TTP) [ Time Frame: Time from first dose to disease progression, assessed up to 2 years ]
    Analysis will be performed using the Kaplan-Meier method. Medians and other quartiles for each endpoint will be estimated in addition to the corresponding two-sided 95% confidence intervals.
  • Duration of Response (DOR) [ Time Frame: Time from first evidence of PR or better to disease progression or death, assessed up to 2 years ]
    Analysis will be performed using the Kaplan-Meier method. Medians and other quartiles for each endpoint will be estimated in addition to the corresponding two-sided 95% confidence intervals.
  • Incidence of adverse events graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 [ Time Frame: Up to 30 days after completion of study treatment ]
    Safety and tolerability will be assessed by incidence, severity, and changes from baseline of all relevant parameters including AEs, laboratory values, and vital signs. AEs will be coded using Medical Dictionary for Regulatory Activities (MedDRA). The number and percentage of patients experiencing 1 or more AEs will be summarized by relationship to study drug and severity. Separate summaries will be created by course and what treatment was received. AEs will be summarized by the number and percentage of patients who experienced the event, according to system organ class and preferred term.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: December 19, 2013)
  • Bone remodeling [ Time Frame: Up to 56 weeks ]
    Measured by sodium fluoride F 18 PET, serum markers of bone remodeling, and the bone marrow osteoblastic and osteoclastic differentiation and function. Will be compared with the measurement of disease response. Paired t-tests will be used to compare 8 and 14 courses correlative endpoints to baseline. Analysis of covariance (ANCOVA) will be used to compare these changes over time between responders and non-responders. If the changes are not normally distributed, non-parametric methods will be used.
  • Proteasome activity in the bone marrow microenvironment [ Time Frame: Up to 56 weeks ]
    Paired t-tests will be used to compare 8 and 14 courses correlative endpoints to baseline. ANCOVA will be used to compare these changes over time between responders and non-responders. If the changes are not normally distributed, non-parametric methods will be used.
  • Response after progressive disease (PD) in maintenance phase [ Time Frame: Up to 56 weeks ]
    Best overall response for each patient will be determined during the recapture response period and summarized descriptively. The disease assessment immediately prior to the first dose of twice-weekly carfilzomib will be used as the baseline, from which response or progression to twice-weekly treatment will be determined.
 
Descriptive Information
Brief Title  ICMJE Carfilzomib in Treating Patients With Multiple Myeloma in First Relapse or Refractory to First-Line Therapy
Official Title  ICMJE A Phase 2 Study of Carfilzomib and Bone Metabolism in Patients With Multiple Myeloma in First Relapse or Refractory to First Line Therapy
Brief Summary This phase II trial studies how well carfilzomib works in treating patients with multiple myeloma in first relapse or refractory to first-line therapy. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Detailed Description

PRIMARY OBJECTIVES:

I. To assess the overall response rate of carfilzomib after 8 cycles of treatment in patients with first-relapsed myeloma.

SECONDARY OBJECTIVES:

I. To assess the overall response rate to single agent carfilzomib after 4 cycles of treatment.

II. To assess progression-free survival (PFS). III. To assess time to progression (TTP). IV. To assess duration of response (DOR). V. To assess toxicities.

TERTIARY OBJECTIVES:

I. To examine the effect of carfilzomib alone or in combination with dexamethasone on the following biologic end points and their correlation with response: measurements of bone remodeling (sodium fluoride F 18 positron emission tomography [PET], serum markers of bone remodeling and the bone marrow osteoblastic and osteoclastic differentiation and function) with the measurement of disease response and proteasome activity in the bone marrow microenvironment.

II. To describe recapture of response after progression in the maintenance phase.

OUTLINE:

TREATMENT PHASE (COURSES 1-8): Patients receive carfilzomib intravenously (IV) over 30 minutes on days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days for 8 courses in the absence of disease progression or unacceptable toxicity. Patients achieving less than partial response (PR) also receive dexamethasone orally (PO) or IV weekly in courses 4-8.

MAINTENANCE PHASE (COURSES 9-14): Patients receive carfilzomib IV over 30 minutes on days 1, 2, 15, and 16. Patients who received dexamethasone in the Treatment Phase continue to receive dexamethasone PO or IV weekly. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 3 months.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Refractory Multiple Myeloma
Intervention  ICMJE
  • Drug: carfilzomib
    Given IV
    Other Names:
    • Kyprolis
    • PR-171
  • Drug: dexamethasone
    Given IV or PO
    Other Names:
    • Aeroseb-Dex
    • Decaderm
    • Decadron
    • DM
    • DXM
  • Other: laboratory biomarker analysis
    Correlative studies
Study Arms  ICMJE Experimental: Treatment (carfilzomib, dexamethasone)

TREATMENT PHASE (COURSES 1-8): Patients receive carfilzomib IV over 30 minutes on days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days for 8 courses in the absence of disease progression or unacceptable toxicity. Patients achieving less than PR also receive dexamethasone PO or IV weekly in courses 4-8.

MAINTENANCE PHASE (COURSES 9-14): Patients receive carfilzomib IV over 30 minutes on days 1, 2, 15, and 16. Patients who received dexamethasone in the Treatment Phase continue to receive dexamethasone PO or IV weekly. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Interventions:
  • Drug: carfilzomib
  • Drug: dexamethasone
  • 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 Terminated
Actual Enrollment  ICMJE
 (submitted: May 12, 2016)
10
Original Estimated Enrollment  ICMJE
 (submitted: December 19, 2013)
35
Actual Study Completion Date  ICMJE April 2016
Actual Primary Completion Date January 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Multiple myeloma (MM) in first relapse or refractory to first line therapy; the previous line of therapy should include either an immunomodulatory agent or a proteasome inhibitor

    • Refractory disease is defined as =< 25% response or progression during therapy or within 60 days after completion
    • The number of prior lines of anti-myeloma therapy will be determined as follows:

      • Induction chemotherapy for peripheral-blood stem cell harvest followed by planned mobilization and subsequent high-dose chemotherapy with autologous stem cell transplant (ASCT) is considered one therapy regardless of the induction regimen
      • Planned maintenance therapy after stem cell transplantation or other induction therapy is not considered a separate line of therapy, as long as there is no evidence of progression in the time between the induction or transplantation and the initiation of maintenance therapy
      • Two ASCTs within 6 months of each other is considered as one line unless different agents were used in the high-dose therapy-conditioning regimens
      • If the same regimen is repeated after a 6-month interval, they are considered to be two separate therapeutic lines
      • If cyclophosphamide is used for reasons other than planned stem cell mobilization, its use is considered to be a separate line of therapy
      • Dose modification of steroid and altering choices of steroid (i.e. from dexamethasone to prednisone) due to side effects, is not considered a line of therapy, as long as there is no evidence of progression
      • If a regimen was stopped for more than 2 months, its re-initiation is counted as another line of therapy
  • Presence of existing lytic bone lesions either by skeletal X-ray, computed tomography (CT) scan or magnetic resonance imaging (MRI) scan
  • Measurable MM disease, defined as one of the following:

    • A monoclonal immunoglobulin (Ig) concentration on serum electrophoresis of >= 0.5 g/dL for an IgG myeloma, >= 0.1 g/dL for an IgD myeloma or >= 0.5 g/dL for an IgA myeloma
    • Measurable urinary light chain secretion by quantitative analysis of >= 200 mg/24 hours
    • Involved serum free light chain (FLC) level >= 10 mg/dL, provided the serum FLC ratio is abnormal
    • Patients with oligo- or non-secretory disease must have bone marrow involvement with at least 30% plasmacytosis on aspiration
  • Life expectancy >= 3 months as determined by the treating physician
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1 or 2
  • Absolute neutrophil count (ANC) >= 1.0 × 10^9/L (without transfusion support and without hematological growth factor support within 2 weeks of cycle 1 day 1)
  • Platelets >= 50 × 10^9/L; if the bone marrow contains >= 50% plasma cells, a platelet count of >= 30 × 10^9/L is allowed (without transfusion support and without hematological growth factor support within 2 weeks of cycle 1 day 1)
  • Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and/or alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) =< 2.5 × the upper limit of normal (ULN)
  • Bilirubin < 2.0 mg/dL
  • Serum creatinine =< 3.0 mg/dL or a calculated creatinine clearance of at least 15 mL/min (using the Cockcroft and Gault method)
  • Adequate cardiac function defined as left ventricular ejection fraction (LVEF) >= 40%

    • NOTE: 2-dimensional (2-D) transthoracic echocardiogram (ECHO) is the preferred method of evaluation
    • Multigated acquisition scan (MUGA) is acceptable if ECHO is not available
  • 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; females are considered of childbearing potential unless they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months
  • Male subjects must agree to practice contraception

Exclusion Criteria:

  • No primary amyloidosis
  • No plasma cell leukemia (> 2.0 × 10^9/L circulating plasma cells by standard differential)
  • No treatment with an investigational product or device within 21 days of cycle 1 day 1
  • No history of allergic reaction/hypersensitivity to any of the study medications, their analogues or excipients in the various formulations
  • No treatment with cytotoxic therapy or monoclonal antibodies within 21 days prior to cycle 1 day 1
  • No treatment with a steroid intended to treat myeloma within 14 days prior to cycle 1 day 1
  • No autologous or allogeneic stem cell transplant within 3 months prior to cycle 1 day 1
  • No radiotherapy within 21 days prior to cycle 1 day 1; however, if the radiation portal covered =< 5% of the bone marrow reserve, the patient may be enrolled irrespective of the end date of radiotherapy
  • No major surgery within 14 days and minor surgery within 7 days prior to cycle 1 day 1
  • No pregnant or lactating females
  • No acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to cycle 1 day 1
  • No known human immunodeficiency virus (HIV) infection
  • No active hepatitis B or C infection
  • No unstable angina or myocardial infarction within 4 months prior to cycle 1 day 1, New York Heart Association (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
  • No uncontrolled hypertension or uncontrolled diabetes (as determined by the treating physician) within 14 days prior to cycle 1 day 1
  • No nonhematologic malignancy within the past 3 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason grade 6 or less with stable prostate-specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder or benign tumors of the adrenal or pancreas
  • No significant neuropathy (grades 3-4, or grade 2 with pain) within 14 days prior to cycle 1 day 1
  • No known history of allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib)
  • No contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to all anticoagulation and antiplatelet options, antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment
  • No subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to cycle 1 day 1
  • Any other clinically significant medical disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02020941
Other Study ID Numbers  ICMJE IUCRO-0414
NCI-2013-01771 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
IUCRO-0414 ( Other Identifier: Indiana University Cancer Center )
P30CA082709 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Attaya Suvannasankha, Indiana University School of Medicine
Study Sponsor  ICMJE Attaya Suvannasankha
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Attaya Suvannasankha Indiana University School of Medicine
PRS Account Indiana University
Verification Date July 2016

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