Study of Velcade and Temsirolimus for Relapsed or Refractory Non-Hodgkin Lymphoma
- Registration Number
- NCT01281917
- Lead Sponsor
- University of Wisconsin, Madison
- Brief Summary
The investigators want to find out if the drugs Velcade and temsirolimus given together are effective in treating cancer. Velcade and temsirolimus are each FDA approved individually for certain types of cancer (Velcade for multiple myeloma and mantle cell lymphoma, and temsirolimus for renal cell carcinoma) but are not currently approved in combination for B-cell non-Hodgkin lymphoma. The investigators are trying to find out if giving these 2 drugs together will improve the period of time that the patient's cancer is stopped or slowed from growing and causing symptoms.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 40
- Relapsed or refractory B-cell non-Hodgkin lymphoma which includes: diffuse large B-cell lymphoma; primary mediastinal large B-cell lymphoma; follicular lymphoma (grade 1, 2 or 3); mantle cell lymphoma; small lymphocytic lymphoma; marginal zone lymphoma; lymphoplasmacytic lymphoma; B-cell lymphoblastic lymphoma; or Burkitt lymphoma. "Grey-zone" lymphomas must be approved by the Wisconsin Oncology Network (WON) Study Chair or Principal Investigator prior to enrollment.
- At least one measurable tumor mass (>1.5 cm in the long axis and > 1.0 cm in the short axis) that has not been previously irradiated, or has grown since previous irradiation.
- Documented relapse or progression following prior antineoplastic therapy.
- No clinical or documented radiographic evidence of central nervous system lymphoma.
- Eastern Cooperative Oncology Group [ECOG] performance status of 0-2.
- The following clinical laboratory values within 14 days prior to enrollment:
- Absolute neutrophil count (ANC) ≥ 1.5 x 109 cells / L
- Platelets ≥ 100 x 109 cells / L
- Alanine transaminase (ALT) and Aspartate transaminase (AST) ≤ 3X the upper limit of normal (ULN)
- Total bilirubin ≤ 2X the upper limit of normal (ULN).
- Calculated creatinine clearance ≥40 mL/min (using the Cockcroft-Gault equation).
- Female subjects must be either post-menopausal for at least 1 year or surgically sterilized, agree to practice 2 effective methods of contraception from the time of signing the informed consent form through 30 days after the last dose of Velcade, or agree to completely abstain from heterosexual intercourse.
- Male subjects, even if surgically sterilized (ie, status postvasectomy) must agree to 1 of the following: practice effective barrier contraception during the entire study treatment period and through a minimum of 30 days after the last dose of study drug, or completely abstain from heterosexual intercourse.
Exclusions:
- Antineoplastic, experimental, or radiation therapy within 14 days prior to enrollment, or 21 days prior to Day 1 of Cycle 1.
- Radioimmunoconjugates within 10 weeks of Day 1 of Cycle 1.
- Autologous stem cell transplant within 3 months before Day 1 of Cycle 1, or any prior history of allogeneic stem cell transplant.
- Platelet transfusion within 7 days of Day 1 of Cycle 1.
- Ongoing therapy with glucocorticoids. Prednisone ≤15 mg per day or its equivalent is allowed.
- Patient has Grade 2 or greater peripheral neuropathy within 14 days before enrollment.
- Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (see section 8.4), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
- Patient has hypersensitivity to Velcade, boron or mannitol.
- Female subjects that are pregnant or breast-feeding.
- Serious medical or psychiatric illness that is likely to interfere with participation
- Diagnosed or treated for another malignancy within 2 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.
- Prior therapy with both Velcade and temsirolimus. Patients who have previously been treated with either Velcade or temsirolimus (but not both) are eligible.
- Radiation therapy within 3 weeks before randomization.
- Patients must not be taking the following strong CyP3A inducers at study entry: phenytoin, phenobarbital, rifampin, carbamazepin, rifabutin, rifampicin, a one week washout period is required.
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Velcade plus Temsirolimus Velcade Velcade 1.6 mg/m2 weekly (days 1, 8, 15, and 22) Temsirolimus 25mg IV weekly (days 1, 8, 15, 22, and 29) Treat for up to 6 cycles, cycles are 35 days long. Velcade plus Temsirolimus Temsirolimus Velcade 1.6 mg/m2 weekly (days 1, 8, 15, and 22) Temsirolimus 25mg IV weekly (days 1, 8, 15, 22, and 29) Treat for up to 6 cycles, cycles are 35 days long.
- Primary Outcome Measures
Name Time Method Overall Response Rate Up to 60 months The primary objective of this study is to determine whether Velcade in combination with temsirolimus provides benefit to subjects with relapsed or refractory B-cell non-Hodgkin lymphoma as assessed by overall response rate (ORR) to therapy. ORR is the sum of patients with a Complete Response and Partial Response to therapy. Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete REsponse (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Progression Free Survival Up to 60 months The primary objective of this study is to determine whether Velcade in combination with temsirolimus provides benefit to subjects with relapsed or refractory B-cell non-Hodgkin lymphoma as assessed by progression-free survival (PFS).
- Secondary Outcome Measures
Name Time Method Safety of This Regimen Up to 36 months Safety of the regimen will be measured by frequency and severity of adverse events.
Complete Response Rate Up to 60 months The complete response rate (CR) to therapy as defined by International Lymphoma Response Criteria.
Tolerability of the Regimen Up to 36 months Tolerability of the regimen is measured by the number of subjects able to complete the therapy as planned.
Duration of Response Up to 60 months Duration of Response is how long a response to therapy is held before a subject has progressive disease.
Overall Survival Up to 60 months Length of time from enrollment until death.
Trial Locations
- Locations (18)
Bellin Memorial Hospital, Inc
🇺🇸Green Bay, Wisconsin, United States
Gunderson Lutheran Health System
🇺🇸La Crosse, Wisconsin, United States
Aurora Baycare Medical Center-GreenBay
🇺🇸Green Bay, Wisconsin, United States
Aspirus Wausau Hospital
🇺🇸Wausau, Wisconsin, United States
Aurora Health Care Metro, Inc.
🇺🇸Wauwatosa, Wisconsin, United States
Aurora Sheboygan Memorial Medical Center
🇺🇸Sheboygan, Wisconsin, United States
Aurora BayCare Medical Center
🇺🇸Marinette, Wisconsin, United States
University Of Wisconsin Cancer Center
🇺🇸Madison, Wisconsin, United States
UW Health Oncology- 1 S Park
🇺🇸Madison, Wisconsin, United States
Rapid City Regional Hospital John T. Vucurevich Cancer Care Institute
🇺🇸Rapid City, South Dakota, United States
Marshfield Clinic
🇺🇸Marshfield, Wisconsin, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Columbia St Mary's, Inc
🇺🇸Milwaukee, Wisconsin, United States
Waukesha Memorial Hospital
🇺🇸Waukesha, Wisconsin, United States
Aurora Medical Center in Summit
🇺🇸Summit, Wisconsin, United States
Aurora Medical Center in Two Rivers
🇺🇸Two Rivers, Wisconsin, United States
UW Cancer Center-Riverview
🇺🇸Wisconsin Rapids, Wisconsin, United States
St Vincent Regional Cancer Center CCOP
🇺🇸Green Bay, Wisconsin, United States