Clinical trial NCT01281917: Study of Velcade and Temsirolimus for Relapsed or Refractory Non-Hodgkin Lymphoma
Official title: A Phase II Study of Velcade and Temsirolimus for Relapsed or Refractory B-cell Non-Hodgkin Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-Hodgkins Lymphoma
Keywords: velcade
temsirolimus
non-hodgkins lymphoma
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: Millennium Pharmaceuticals, Inc.
name: Pfizer
name: National Cancer Institute (NCI)
First posted: 2011-01-24
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Primary outcomes:
measure: Overall Response Rate
timeFrame: Up to 60 months
measure: Progression Free Survival
timeFrame: Up to 60 months
Secondary outcomes:
measure: Safety of This Regimen
timeFrame: Up to 36 months
measure: Complete Response Rate
timeFrame: Up to 60 months
measure: Tolerability of the Regimen
timeFrame: Up to 36 months
measure: Duration of Response
timeFrame: Up to 60 months
measure: Overall Survival
timeFrame: Up to 60 months
Other outcomes:
Locations:
city: Rapid City
country: United States
facility: Rapid City Regional Hospital John T. Vucurevich Cancer Care Institute
state: South Dakota
city: Green Bay
country: United States
facility: Aurora Baycare Medical Center-GreenBay
state: Wisconsin
city: Green Bay
country: United States
facility: St Vincent Regional Cancer Center CCOP
state: Wisconsin
city: Green Bay
country: United States
facility: Bellin Memorial Hospital, Inc
state: Wisconsin
city: La Crosse
country: United States
facility: Gunderson Lutheran Health System
state: Wisconsin
city: Madison
country: United States
facility: UW Health Oncology- 1 S Park
state: Wisconsin
city: Madison
country: United States
facility: University Of Wisconsin Cancer Center
state: Wisconsin
city: Marinette
country: United States
facility: Aurora BayCare Medical Center
state: Wisconsin
city: Marshfield
country: United States
facility: Marshfield Clinic
state: Wisconsin
city: Milwaukee
country: United States
facility: Columbia St Mary's, Inc
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Sheboygan
country: United States
facility: Aurora Sheboygan Memorial Medical Center
state: Wisconsin
city: Summit
country: United States
facility: Aurora Medical Center in Summit
state: Wisconsin
city: Two Rivers
country: United States
facility: Aurora Medical Center in Two Rivers
state: Wisconsin
city: Waukesha
country: United States
facility: Waukesha Memorial Hospital
state: Wisconsin
city: Wausau
country: United States
facility: Aspirus Wausau Hospital
state: Wisconsin
city: Wauwatosa
country: United States
facility: Aurora Health Care Metro, Inc.
state: Wisconsin
city: Wisconsin Rapids
country: United States
facility: UW Cancer Center-Riverview
state: Wisconsin
Study officials:
affiliation: Universtity of Wisconsin- Madison
name: Brad S Kahl, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical College of Wisconsin
name: Timothy S Fenske, MD
role: STUDY_CHAIR
References: