Carfilzomib, Rituximab and Dexamethasone in Waldenstrom's Macroglobulinemia (CaRD)
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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 |
- Response Rates [ Time Frame: 1 year ] [ 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: 1 year ] [ 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: 1 year ] [ 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: 1 year ] [ 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: | December 2013 |
| Estimated Primary Completion Date: | December 2012 (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 |
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| United States, Massachusetts | |
| Dana-Farber Cancer Institute | |
| Boston, Massachusetts, United States, 02215 | |
| Principal Investigator: | Steven P Treon, MD, PhD | Dana-Farber Cancer Institute |
More Information
No publications provided
| 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: | December 19, 2012 |
| 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 May 23, 2013