Phase 2
N=7
A Phase II Study of Carfilzomib in Relapsed Waldenström's Macroglobulinemia (WM) IST-CAR-531
Waldenstrom Macroglobulinemia
Bottom Line
View on ClinicalTrials.gov: NCT01813227 ↗Enrolled (actual)
7
Serious AEs
14.3%
Results posted
Apr 2022
Primary outcome: Primary: Overall Response Rate (ORR) of Carfilzomib in Bortezomib naïve and Bortezomib-exposed Relapsed WM — 85.7 percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Carfilzomib (Drug); Rituximab (Drug); Dexamethasone (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Hackensack Meridian Health
- Primary completion
- Sep 2014
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Overall Response Rate (ORR) of Carfilzomib in Bortezomib naïve and Bortezomib-exposed Relapsed WM |
85.7 | — |
| SECONDARY Number of Patients Experiencing Dose Limiting Toxicity |
— | — |
| SECONDARY Duration of Response in Patients With WM. |
15.4 | — |
| SECONDARY Time to Progression |
16 | — |
| SECONDARY Progression Free Survival |
19.4 | — |
Summary
The purpose of this study is to evaluate the safety and effectiveness of an investigational study drug called carfilzomib. The investigators want to find out what effects, good and/or bad, it has on patients and their cancer if treatment continues beyond previous carfilzomib treatment study.
Carfilzomib (KyprolisTM) is approved by the U.S. Food and Drug Administration (FDA) to be used only in certain U.S. patients with relapsed and refractory multiple myeloma that have tried and failed other therapies. It has not been approved to be used for any other disease or condition.
In this study, carfilzomib is referred to as an investigational study drug because it is not approved for use in all patients with multiple myeloma in the United States, and it is not approved by some regulatory authorities (the agencies that are responsible for approving the use of a medicine in a country such as Health Canada).
Carfilzomib is a type of drug called a proteasome inhibitor. A proteasome is a protein found within cells that has the important role of identifying and marking damaged proteins that are needed to be destroyed by the cell for survival. The inhibition of the proteasome allows for damaged protein to accumulate within cells. This accumulation of damaged protein causes the cell to die.
Eligibility Criteria
Inclusion Criteria
- Biopsy proven WM with relapsed/refractory symptomatic disease are eligible for enrollment.
- Bone marrow lymphoplasmacytosis with:
- > 10% lymphoplasmacytic cells (measured within 28 days prior to registration OR
- Aggregates or sheets of one of the following: lymphocytes, plasma cells or lymphoplasmacytic cells on the bone marrow biopsy (measured within 28 days prior to registration).
- Measurable disease defined as a quantitative IgM monoclonal protein of >500 mg/dL obtained within 28 days prior to registration
- CD20+ bone marrow or lymph node by immunohistochemistry or flow cytometry obtained within 28 days prior to registration
- Lymph node biopsy must be done 10 mg prednisone (or equivalent) per day.
- Prior irradiation is allowed if > 28 days prior to registration have elapsed since the date of last treatment.
- Women must not be pregnant or breast-feeding due to the fact that the reproductive risk to humans taking carfilzomib is unknown. All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy. A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
- Women of childbearing potential and sexually active males must use an accepted and effective method of contraception throughout the study and for 8 weeks after completion of the study.
- Patients must be > 18 years old.
- Patients must have ECOG performance status of 50%) within 14 days prior to randomization
- Creatinine clearance (CrCl) ≥ 15 mL/minute within 7 days prior to randomization, either measured or calculated using a standard formula (e.g., Cockcroft and Gault)
Exclusion Criteria
- Pre-existing peripheral neuropathy > grade 2 with pain (CTC version 4.0).
- Hematologic criteria: ANC 3x institutional ULN
- Direct bilirubin > 1.5 mg/dL
- Patients must not have any severe and/or uncontrolled medical condition or other conditions that could affect their participation in the study, including, but not restricted to:
- Symptomatic congestive heart failure of New York Heart Association Class III or IV.
- Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 3 months of start of study treatment, serious uncontrolled cardiac arrhythmia or any other clinically significant heart disease.
- Severely impaired lung function as defined as spirometry and DLCO (corrected for Hgb) that is <50% of the normal predicted value and/or O2 saturation <88% at rest on room air.
- Active (acute or chronic) or uncontrolled severe infections.
Data sourced from ClinicalTrials.gov (NCT01813227). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.