Non-Hodgkins Lymphoma
Conditions
Keywords
velcade, temsirolimus, non-hodgkins lymphoma
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.
Interventions
DRUGVelcade
Velcade, 1.6 mg/m2 weekly (days 1, 8, 15, and 22)
DRUGTemsirolimus
Temsirolimus 25mg IV weekly (days 1, 8, 15, 22, and 29)
Sponsors
Millennium Pharmaceuticals, Inc.
Pfizer
National Cancer Institute (NCI)
University of Wisconsin, Madison
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Safety of This Regimen | Up to 36 months | Safety of the regimen will be measured by frequency and severity of adverse events. |
| Overall Survival | Up to 60 months | Length of time from enrollment until death. |
| 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. |
| Complete Response Rate | Up to 60 months | The complete response rate (CR) to therapy as defined by International Lymphoma Response Criteria. |
Countries
United States
Participant flow
Recruitment details
Patients with relapsed or refractory B-cell NHL were enrolled from 10 sites within the Wisconsin Oncology Network (WON) between May 2011 and May 2013.
Pre-assignment details
Forty participants were enrolled from 10 sites within the Wisconsin Oncology Network (WON) over 2 years. One participant withdrew consent immediately after enrollment and was never treated. Therefore, results are reported on the remaining 39 participants.
Participants by arm
| Arm | Count |
|---|---|
| Velcade Plus 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.
Velcade: Velcade, 1.6 mg/m2 weekly (days 1, 8, 15, and 22)
Temsirolimus: Temsirolimus 25mg IV weekly (days 1, 8, 15, 22, and 29) | 39 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Velcade Plus Temsirolimus |
|---|---|
| Age, Continuous | 68 years |
| ECOG Performance Status 0 | 17 Participants |
| ECOG Performance Status 1 | 16 Participants |
| ECOG Performance Status 2 | 6 Participants |
| Histology DLBCL | 18 Participants |
| Histology Follicular lymphoma | 9 Participants |
| Histology Mantle cell lymphoma | 7 Participants |
| Histology Marginal zone lymphoma | 2 Participants |
| Histology Small lymphocytic lymphoma | 3 Participants |
| Number of prior treatments | 4 Prior treatments |
| Region of Enrollment United States | 39 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 16 / 39 |
| other Total, other adverse events | 35 / 39 |
| serious Total, serious adverse events | 18 / 39 |
Outcome results
Primary
Overall Response Rate
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.
Time frame: Up to 60 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Velcade Plus Temsirolimus | Overall Response Rate | 31 Percentage of participants |
Primary
Progression Free Survival
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).
Time frame: Up to 60 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Velcade Plus Temsirolimus | Progression Free Survival | 4.7 Months |
Secondary
Complete Response Rate
The complete response rate (CR) to therapy as defined by International Lymphoma Response Criteria.
Time frame: Up to 60 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Velcade Plus Temsirolimus | Complete Response Rate | 3 Participants |
Secondary
Duration of Response
Duration of Response is how long a response to therapy is held before a subject has progressive disease.
Time frame: Up to 60 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Velcade Plus Temsirolimus | Duration of Response | 7 months |
Secondary
Overall Survival
Length of time from enrollment until death.
Time frame: Up to 60 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Velcade Plus Temsirolimus | Overall Survival | 14.1 Months |
Secondary
Safety of This Regimen
Safety of the regimen will be measured by frequency and severity of adverse events.
Time frame: Up to 36 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Velcade Plus Temsirolimus | Safety of This Regimen | Grade 3 Adverse Events | 31 Participants |
| Velcade Plus Temsirolimus | Safety of This Regimen | Grade 4 Adverse Events | 2 Participants |
| Velcade Plus Temsirolimus | Safety of This Regimen | No Grade 3/4 Adverse Events | 6 Participants |
Secondary
Tolerability of the Regimen
Tolerability of the regimen is measured by the number of subjects able to complete the therapy as planned.
Time frame: Up to 36 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Velcade Plus Temsirolimus | Tolerability of the Regimen | Discontinued study due to an adverse event | 5 Participants |
| Velcade Plus Temsirolimus | Tolerability of the Regimen | Continued study | 34 Participants |