"Help us test safety and dosing of combination treatment for Non-Hodgkin lymphoma that has returned or did not respond to treatment"
18 to 100 years old
Drug study, Phase 1
The purpose of this study is to test the safety of an investigational drug, carfilzomib, at different dose levels when combined with bendamustine and rituximab. We want to find out what effects, good and/bad, the combination has on you and your Non-Hodgkins lymphoma (NHL).
The study drug, carfilzomib, is an investigational drug. Investigational means that this drug has not been approved by the US Food and Drug Administration (FDA) for use in NHL. Carfilzomib belongs to a class of drugs called ‘proteasome inhibitors’. This class of drugs has shown activity against NHL in other clinical trials. Carfilzomib has been studied in NHL alone and in combination with other drugs. Bendamustine (targeted chemotherapy) is approved by the FDA for the treatment of patients with indolent B-cell NHL that has progressed and for the treatment of patients with chronic lymphocytic leukemia (CLL). Rituximab(a type of immunotherapy) is approved by the FDA for the treatment of diffuse large B-cell, CD20-positive NHL, Low-grade or follicular B-cell, CD20-positive NHL, and Chronic Lymphocytic Leukemia (CLL).
The combination of carfilzomib with bendamustine and rituximab is considered investigational, which means it has not been approved for use by the FDA.
This study requires
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Who can participate?
- Histologically-confirmed B-cell non-Hodgkin's lymphoma (Mantle Cell Lymphoma, Follicular Lymphoma, Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia, Marginal Zone Lymphoma, Diffuse Large B-cell Lymphoma, and Lymphoplasmacytic Lymphoma)
- Must have relapsed or refractory disease after 2 but not more than 4 prior lines of therapy; 1 line of therapy is allowed, if it included an autologous stem cell transplant and at least 12 weeks have elapsed from Day 0. A line of therapy is defined as a course of therapy that is not interrupted by progressive disease.
- Subjects must have measurable disease of at least 1.5 cm in diameter
- Age ≥ 18 years
- Life expectancy ≥ 3 months
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Adequate bone marrow function:
Absolute neutrophil count ≥ 1.0 × 109/L Hemoglobin ≥ 8 g/dL (80 g/L) within 14 days prior Cycle 1, Day 1 (subjects may be receiving red blood cell [RBC] transfusions in accordance with institutional guidelines) Platelet count ≥ 75 × 109/L or≥ 50× 109/L if there is lymphoma involvement in the bone marrow, independent of platelet transfusion
Adequate hepatic function:
Serum AST/ALT ≤ 3 times the upper limit of normal Serum direct bilirubin ≤ 2 mg/dL (unless history of Gilbert's)
Adequate renal function:
Creatinine clearance (CrCl) ≥ 30 mL/minute, either measured or calculated using a standard formula (eg, Cockcroft and Gault) Uric acid If elevated, corrected to within laboratory range prior to dosing
- Females of childbearing potential (FCBP) must agree to ongoing pregnancy testing and to practice contraception. FCBP definition: A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months.
- Male subjects must agree to practice contraception.
- Progressive disease on bendamustine within 6 months of cycle 1, Day 1
- Prior treatment with carfilzomib for lymphoma
- Patient has received other investigational drugs within 21 days prior to Cycle 1, Day 1. Exceptions allowed if greater than four half-lives of the experimental agent ).
- Prior radiation therapy or chemotherapy within 2 weeks prior Cycle 1, Day 1, monoclonal antibody therapy within 4 weeks
- Prior allogeneic transplant
- Active, uncontrolled CNS involvement by lymphoma
- Pregnant or lactating females
- Major surgery within 14 days prior Cycle 1, Day 1
- Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior Cycle 1, Day 1
- Known human immunodeficiency virus infection
- Active hepatitis C infection, defined as presence of HCV antibody.
- Unstable angina or myocardial infarction within 6 months prior Cycle 1, Day 1, NYHA Class III or IV heart failure, LVEF < 40%, uncontrolled angina, history of severe coronary artery disease, history of torsade de pointes, history of symptomatic pulmonary hypertension, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, QTc prolongation >450 msec, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless subject has a pacemaker.
- Uncontrolled hypertension or uncontrolled diabetes within 14 days prior Cycle 1, Day 1
- Nonhematologic malignancy within the past 3 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or less with stable prostate-specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder or benign tumors of the adrenal or pancreas
- Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior Cycle 1, Day 1
- Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib)
- 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
- Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior Cycle 1, Day 1
- Any other clinically significant medical disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent.