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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Onyx Pharmaceuticals
Information provided by (Responsible Party):
Steven P. Treon, MD, PhD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT01470196
First received: September 22, 2011
Last updated: June 11, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Waldenstrom's Macroglobulinemia
Drug: Dexamethasone
Drug: Carfilzomib
Drug: Rituximab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Carfilzomib, Rituximab, and Dexamethasone (CaRD) in Waldenstrom's Macroglobulinemia

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Response Rates [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    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: 3 years ] [ Designated as safety issue: No ]
    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: 3 years ] [ Designated as safety issue: Yes ]
    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: 5 years ] [ Designated as safety issue: No ]
    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


Estimated Enrollment: 30
Study Start Date: October 2011
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CARD STUDY
Only one arm in this study
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01470196

Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Dana-Farber Cancer Institute
Onyx Pharmaceuticals
Investigators
Principal Investigator: Steven P Treon, MD, PhD Dana-Farber Cancer Institute
  More Information

No publications provided by Dana-Farber Cancer Institute

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Steven P. Treon, MD, PhD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT01470196     History of Changes
Other Study ID Numbers: 11-279
Study First Received: September 22, 2011
Last Updated: June 11, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:
WM
untreated
symptomatic

Additional relevant MeSH terms:
Waldenstrom Macroglobulinemia
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Rituximab
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids

ClinicalTrials.gov processed this record on September 22, 2014