Carfilzomib, Rituximab and Dexamethasone in Waldenstrom's Macroglobulinemia

NCT ID: NCT01470196

Last Updated: 2018-11-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-10-31
• Study Completion Date: 2016-09-30

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.

Conditions

Waldenstrom's Macroglobulinemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment Arm

Carfilzomib, dexamethasone, rituximab

Group Type: EXPERIMENTAL

Dexamethasone

Intervention Type: DRUG

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

Carfilzomib

Intervention Type: DRUG

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

Rituximab

Intervention Type: DRUG

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

Interventions

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

Intervention Type: 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

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

Decadron; PR-171; Rituxan

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: collaborator

Dana-Farber Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Steven P. Treon, MD, PhD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Steven P Treon, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Countries

United States

References

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 Waldenstrom's macroglobulinemia. Blood. 2014 Jul 24;124(4):503-10. doi: 10.1182/blood-2014-03-566273. Epub 2014 May 23.

Reference Type: DERIVED

PMID: 24859363 (View on PubMed)

Other Identifiers

11-279

Identifier Type: -

Identifier Source: org_study_id