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Carfilzomib, Rituximab and Dexamethasone in Waldenstrom's Macroglobulinemia (CaRD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01470196
Recruitment Status : Completed
First Posted : November 11, 2011
Results First Posted : May 1, 2017
Last Update Posted : June 9, 2017
Sponsor:
Collaborator:
Information provided by (Responsible Party):

September 22, 2011
November 11, 2011
March 20, 2017
May 1, 2017
June 9, 2017
October 2011
September 2016   (Final data collection date for primary outcome measure)
  • Overall Response Rate [ Time Frame: 4 years ]
    Overall Response Rate= Minor response (>25%-50% reduction in serum IgM from baseline + Partial Response (>50-90% reduction in serum IgM from baseline) + Very Good Partial Response (>90% reduction in serum IgM from baseline) + Complete Response (resolution of all symptoms, normalization of serum IgM with disappearance of IgM paraprotein, resolution of any adenopathy or splenomegaly).
  • Neuropathy Incidence Rate [ Time Frame: 3 years ]
    Number and percentage of participants who experienced neuropathy attributable to CaRD therapy
  • Time to Progression [ Time Frame: 4 years ]
    Progression-free survival is the defined as the time from study entry to disease progression (PD) or death. Patients without PD are censored at the date of last disease evaluation. PD is defined as a greater than 25% increase in serum IgM and 500mg/dL absolute increase from the lowest attained response value as determined by serum electrophoresis, confirmed by at least one other investigation, or progression of clinically significant disease related symptom(s).
  • Major Response Rate [ Time Frame: 4 years ]
    Major Response Rate= Partial Response (>50-90% reduction in serum IgM from baseline) + Very Good Partial Response (>90% reduction in serum IgM from baseline) + Complete Response (resolution of all symptoms, normalization of serum IgM with disappearance of IgM paraprotein, resolution of any adenopathy or splenomegaly).
  • Very Good Partial Response and Complete Response Rate [ Time Frame: 4 years ]
    This is the rate of VGPR and CR in patients on CaRD therapy. Very good partial responses are >90% reduction in serum IgM from baseline. Complete response is defined as having resolution of all symptoms, normalization of serum IgM levels with complete disappearance of IgM paraprotein by immunofixation, and resolution of any adenopathy or splenomegaly.
  • Response Rates [ Time Frame: 1 year ]
    To assess the overall response rate (ORR), major response rate (MRR), and Very Good Partial Response/Complete Response (VGPR/CR) rates of CaRD in symptomatic untreated on symptomatic pretreated but proteasome inhibitor and rituximab naive, WM patients.
  • Neuropathy Incidence Rate [ Time Frame: 1 year ]
    To determine the neuropathy incidence rate attributable to CaRD in symptomatic untreated or symptomatic pretreated but proteasome inhibitor and rituximab naive, WM patients
  • Safety and Tolerability [ Time Frame: 1 year ]
    To assess the safety and tolerability of CaRD in symptomatic untreated or symptomatic pretreated but proteasome inhibitor and rituximab naive, WM patients
  • Time to Progression [ Time Frame: 1 year ]
    To determine the Time to Progression (TTP), and Time to Next Therapy (TNT) of CaRD in symptomatic untreated or symptomatic pretreated but proteasome inhibitor and rituximab naive, WM patients
Complete list of historical versions of study NCT01470196 on ClinicalTrials.gov Archive Site
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Carfilzomib, Rituximab and Dexamethasone in Waldenstrom's Macroglobulinemia
Carfilzomib, Rituximab, and Dexamethasone (CaRD) in Waldenstrom's Macroglobulinemia

Carfilzomib is a drug that has shown anti-tumor activity by inhibiting the proteasome within the cell, which is responsible for degrading or breaking down a wide variety of proteins. Carfilzomib has not been approved by the FDA.

Rituximab and dexamethasone are often used to treat Waldenstrom's Macroglobulinemia (WM), alone or in combination with other drugs. Combinations with rituximab, dexamethasone and proteasome inhibitors, like carfilzomib, show high levels of activity in WM patients.

In this research study, the investigators are testing the safety and efficacy of Carfilzomib when used along with Rituximab and Dexamethasone as a possible treatment for Waldenstrom's Macroglobulinemia.

If you take part in this research study, you will receive Carfilzomib and dexamethasone as an infusion on Days 1, 2, 8, and 9 for Cycles 1-6. You will then have a Rituximab infusion on Days 2 and 9. Each cycles lasts 21 days. After completing Cycle 6 and if you are eligible, there will be a 2 month break before the maintenance phase is started. During this break, you will have a study visit with a physical exam, blood tests, and a bone marrow biopsy. If you continue to the maintenance phase, you will receive Carfilzomib and Dexamethasone on Days 1 and 2 and Rituximab on Day 2 of Cycles 1-8. Each cycle will continue to last 21 days, but will take place every 2 months. Infusions will last between 2-6 hours.

During all cycles you will have a physical exam and you will be asked questions about your general health and specific questions about any problems that you might be having and any medications you may be taking. Blood tests will also be done at each Cycle visit, and you will complete a questionnaire. Bone marrow and CT scan will only be repeated at physician discretion when appropriate and in order to ensure your response to treatment.

Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Waldenstrom's Macroglobulinemia
  • Drug: Dexamethasone
    20 mg IV on Days 1, 2, 8, 9, of 21 day cycle for cycles 1-6 20 mg IV on Days 1, 2 of 21 day cycles q 2 months for cycles 1-8
    Other Name: Decadron
  • Drug: Carfilzomib
    20 mg/m2 IV on Days 1, 2, 8, 9 of 21 day cycles for Cycle 1 36 mg/m2 IV on Days 1, 2, 8, 9 of 21 day cycles for Cycles 2-6 36 mg/m2 IV on Days 1, 2 of 21 day cycles q 2 months for Cycles 1-8
    Other Name: PR-171
  • Drug: Rituximab
    375 mg/m2 IV on Days 2, 9 of 21 day cycles for Cycles 1-6 375 mg/m2 IV on Day 2 of 21 day cycles q 2 months for Cycles 1-8
    Other Name: Rituxan
Experimental: Treatment Arm
Carfilzomib, dexamethasone, rituximab
Interventions:
  • Drug: Dexamethasone
  • Drug: Carfilzomib
  • Drug: Rituximab
Treon SP, Tripsas CK, Meid K, Kanan S, Sheehy P, Chuma S, Xu L, Cao Y, Yang G, Liu X, Patterson CJ, Warren D, Hunter ZR, Turnbull B, Ghobrial IM, Castillo JJ. Carfilzomib, rituximab, and dexamethasone (CaRD) treatment offers a neuropathy-sparing approach for treating Waldenström's macroglobulinemia. Blood. 2014 Jul 24;124(4):503-10. doi: 10.1182/blood-2014-03-566273. Epub 2014 May 23.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
31
September 2016
September 2016   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Diagnosis of Waldenstrom's Macroglobulinemia
  • Symptomatic disease
  • Measurable disease
  • Life expectancy of greater than 12 weeks
  • Adequate organ and marrow function
  • CD20 positive based on any previous performed bone marrow immunohistochemistry or flow cytometric analysis
  • Disease free of prior malignancies for >/= 5 years with the exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast

Exclusion Criteria:

  • More than one prior therapy
  • Previous therapy with a proteasome inhibitor or rituximab
  • Chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Currently receiving treatment for any malignancy
  • Major surgery within 21 days prior to study entry
  • Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to study entry
  • Uncontrolled hypertension or uncontrolled diabetes
  • Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior to study entry
  • Known history of allergy to Captisol
  • Receiving any other study agents
  • Known brain metastases
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to carfilzomib, rituximab, and/or dexamethasone
  • 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
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant or lactating
  • HIV-positive on combination antiretroviral therapy
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01470196
11-279
Yes
Not Provided
Plan to Share IPD: Undecided
Steven P. Treon, MD, PhD, Dana-Farber Cancer Institute
Dana-Farber Cancer Institute
Amgen
Principal Investigator: Steven P Treon, MD, PhD Dana-Farber Cancer Institute
Dana-Farber Cancer Institute
May 2017

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