Carfilzomib, Rituximab and Dexamethasone in Waldenstrom’s Macroglobulinemia

Brief Title

Carfilzomib, Rituximab and Dexamethasone in Waldenstrom's Macroglobulinemia

Official Title

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

Brief Summary

      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.
    

Detailed Description

      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.
    

Study Phase

Phase 2

Study Type

Interventional

Primary Outcome

Overall Response Rate

Condition

Waldenstrom's Macroglobulinemia

Intervention

Dexamethasone

Study Arms / Comparison Groups

 Treatment Arm

Description:  Carfilzomib, dexamethasone, rituximab

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

31

Start Date

October 2011

Completion Date

September 2016

Primary Completion Date

September 2016

Eligibility Criteria

        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
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Steven P Treon, MD, PhD, , 

Location Countries

United States

Location Countries

United States

NCT ID

NCT01470196

Organization ID

11-279

Responsible Party

Principal Investigator

Study Sponsor

Dana-Farber Cancer Institute

Collaborators

 Amgen

Study Sponsor

Steven P Treon, MD, PhD, Principal Investigator, Dana-Farber Cancer Institute

Verification Date

October 2018