Carfilzomib, Rituximab and Dexamethasone in Waldenstrom's Macroglobulinemia

NCT01470196 | Completed Phase 2 Results DMC

• 1 other identifier: 11-279
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

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.

Conditions

Waldenstrom's Macroglobulinemia

Keywords

WM; untreated; symptomatic

Outcome Measures

Primary Outcomes (5)

• Overall Response Rate

  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).

  4 years

• Neuropathy Incidence Rate

  Number and percentage of participants who experienced neuropathy attributable to CaRD therapy

  3 years

• Time to Progression

  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).

  4 years

• Major Response Rate

  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).

  4 years

• Very Good Partial Response and Complete Response Rate

  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.

  4 years

Study Arms (1)

Treatment Arm

EXPERIMENTAL

Carfilzomib, dexamethasone, rituximab

Drug: Dexamethasone; Drug: Carfilzomib; Drug: Rituximab

Interventions

Dexamethasone 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

Also known as: Decadron

Treatment Arm

Carfilzomib 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

Also known as: PR-171

Treatment Arm

Rituximab 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

Also known as: Rituxan

Treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Amgen: collaborator

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• 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.

  PMID: 24859363 DERIVED

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia

Interventions

Dexamethasone; Calcium Dobesilate; carfilzomib; Rituximab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Steven P. Treon, MD, PhD
• Organization: Dana-Farber Cancer Institute

steven_treon@dfci.harvard.edu

617-632-2681

Study Officials

• Steven P Treon, MD, PhD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 22, 2011
• First Posted: November 11, 2011
• Study Start: October 1, 2011
• Primary Completion: September 1, 2016
• Study Completion: September 1, 2016
• Last Updated: November 20, 2018
• Results First Posted: March 21, 2017

Record last verified: 2018-10

Locations

US (1)