B-cell Chronic Lymphocytic Leukemia, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Malignant Neoplasm, Nodal Marginal Zone B-cell Lymphoma, Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Diffuse Mixed Cell Lymphoma, Recurrent Adult Diffuse Small Cleaved Cell Lymphoma, Recurrent Adult Immunoblastic Large Cell Lymphoma, Recurrent Adult Lymphoblastic Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Marginal Zone Lymphoma, Recurrent Small Lymphocytic Lymphoma, Refractory Chronic Lymphocytic Leukemia, Splenic Marginal Zone Lymphoma, Waldenström Macroglobulinemia
Conditions
Brief summary
Drugs used in chemotherapy, such as CCI-779, work in different ways to stop cancer cells from dividing so they stop growing or die. This phase II trial is studying how well CCI-779 works in treating patients with recurrent or refractory B-cell non-Hodgkin's lymphoma or chronic lymphocytic leukemia.
Detailed description
PRIMARY OBJECTIVES: I. Determine the complete and partial response rate in patients with recurrent or refractory B-cell non-Hodgkin's lymphoma or chronic lymphocytic leukemia treated with CCI-779. II. Determine the toxicity and safety of this drug in these patients. III. Correlate the degree of activation of P13/AKT/mTOR pathway and levels of CDK inhibitors with response in patients treated with this drug. IV. Correlate CCI-779 induced inactivation of mTOR with response in these patients. OUTLINE: Patients are stratified according to disease (aggressive lymphoma \[group A\] vs follicular lymphoma \[group B\] vs small lymphocytic lymphoma or chronic lymphocytic leukemia \[group C\]). Patients receive CCI-779 IV over 30 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 8 weeks.
Interventions
DRUGtemsirolimus
Sponsors
National Cancer Institute (NCI)
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
* Histologically or cytologically confirmed B-cell non-Hodgkin's lymphoma, including the following subtypes: * Aggressive B-cell lymphoma (Group A) * Diffuse large B-cell lymphoma * Transformed lymphoma * Follicular lymphoma (Group B) * Small lymphocytic lymphoma * Chronic lymphocytic leukemia (CLL) (Group C) * Other B-cell small lymphocytic disorders * No mantle cell lymphoma * No potentially curative treatment options because of lack of response, relapse, or ineligibility * Relapsed or refractory disease * Patients with refractory disease (i.e., less than a partial response to the last treatment) must have received no more than 3 prior regimens (group A) * Patients with sensitive disease (i.e., at least a partial response to the last treatment) must have received no more than 4 prior regimens (group A) * Patients who have failed prior autologous transplantation are eligible (group A) * No more than 5 prior regimens (groups B and C) * The salvage regimen, conditioning regimen, and any maintenance therapy are considered 1 regimen * Prior rituximab or alemtuzumab is not considered prior therapy * No limitation to the amount of prior radiotherapy * No CNS involvement * Performance status: ECOG 0-2 OR Karnofsky 60-100% * Life expectancy more than 3 months * No symptomatic congestive heart failure * No unstable angina pectoris * No cardiac arrhythmia * No prior allergic reactions attributed to compounds of similar chemical or biological composition to CCI-779 * No ongoing or active infection * No psychiatric illness or social situation that would preclude study compliance * No other active malignancy except nonmelanoma skin cancer or carcinoma in situ of the cervix Completed therapy and considered \< 30% risk of relapse * No other concurrent uncontrolled illness * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No concurrent prophylactic hematopoietic colony-stimulating factors * No concurrent pegfilgrastim * More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered * More than 4 weeks since prior radiotherapy and recovered * No concurrent combination antiretroviral therapy for HIV-positive patients * No concurrent unconventional therapies, food, or vitamin supplements containing Hypericum perforatum (St. John's wort) * No other concurrent known inducers of CYP3A4 * No other concurrent investigational agents * No other concurrent anticancer therapy * Measurable disease\* * At least 1 unidimensionally measurable lesion \>= 20 mm by conventional techniques OR \>= 10 mm by spiral CT scan \[Note: \*Only bone marrow or peripheral blood involvement required for CLL and Waldenstrom's macroglobulinemia \] * Absolute neutrophil count \>= 1,000/mm3 * Bilirubin =\< 1.5 times upper limit of normal (ULN) * AST and ALT =\< 2.5 times ULN * Creatinine =\< 1.5 times ULN * Fasting cholesterol =\< 350 mg/dL * Fasting triglycerides =\< 400 mg/dL * Platelet count \>= 50, 000/mm3 (\> 20,000/mm3 for patients with thrombocytopenia due to bone marrow involvement)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Overall Response Rate | Up to 6 years | The 1999 international response criteria (http://www.ncbi.nlm.nih.gov/pubmed/10655437#) as published by Cheson was used for the definition of target lesions and CT scans were used for response assessment. CR(complete response)/CRu(unconfirmed complete response) requires disappearance of all target lesions; PR (partial response) requires \>=50% decrease in the sum of the products of the greatest diameters; Overall Response (OR)=CR/CRu+PR. |
| Duration of Response | Up to 6 years | Duration of response was the time from date of response to date of progression and evaluated among participants with response. According to the 1999 international response criteria as published by Cheson, progression/progressive disease is defined as \>=50% increase from nadir in the sum of the products of the greatest diameters of any previously identified abnormal node for PRs or nonresponders, or appearance of any new lesion during or at the end of therapy. |
| Overall Survival | Up to 6 years | The overall survival was evaluated using the Kaplan-Meier estimator. |
Countries
United States
Participant flow
Pre-assignment details
One patient never received protocol treatment and was excluded from analysis.
Participants by arm
| Arm | Count |
|---|---|
| Aggressive B-cell Lymphoma Patients received Temsirolimus (CCI-779) IV over 30 minutes on days 1,8,15, and 22. Courses repeated every 28 days in the absence of disease progression or unacceptable toxicity. Patients were followed every 8 weeks. Aggressive B-cell lymphoma group was defined as patients with histologic subtypes included diffuse large B-cell lymphoma and transformed follicular lymphoma. | 32 |
| Follicular Lymphoma Patients received Temsirolimus (CCI-779) IV over 30 minutes on days 1,8,15, and 22. Courses repeated every 28 days in the absence of disease progression or unacceptable toxicity. Patients were followed every 8 weeks. Follicular lymphoma group was defined as patients with histologic subtypes included follicular lymphoma. | 39 |
| Chronic Lymphocytic Leukemia Patients received Temsirolimus (CCI-779) IV over 30 minutes on days 1,8,15, and 22. Courses repeated every 28 days in the absence of disease progression or unacceptable toxicity. Patients were followed every 8 weeks. Chronic lymphocytic leukemia group was defined as patients with histologic subtypes included chronic lymphocytic leukemia, small lymphocytic lymphoma, and other indolent lymphomas. | 18 |
| Total | 89 |
Baseline characteristics
| Characteristic | Aggressive B-cell Lymphoma | Follicular Lymphoma | Chronic Lymphocytic Leukemia | Total |
|---|---|---|---|---|
| Age, Continuous | 67 years | 59 years | 57 years | 61 years |
| Sex: Female, Male Female | 15 Participants | 15 Participants | 7 Participants | 37 Participants |
| Sex: Female, Male Male | 17 Participants | 24 Participants | 11 Participants | 52 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 89 / 89 |
| serious Total, serious adverse events | 21 / 89 |
Outcome results
Primary
Duration of Response
Duration of response was the time from date of response to date of progression and evaluated among participants with response. According to the 1999 international response criteria as published by Cheson, progression/progressive disease is defined as \>=50% increase from nadir in the sum of the products of the greatest diameters of any previously identified abnormal node for PRs or nonresponders, or appearance of any new lesion during or at the end of therapy.
Time frame: Up to 6 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Aggressive B-cell Lymphoma | Duration of Response | 2.4 Month |
| Follicular Lymphoma | Duration of Response | 13.3 Month |
| Chronic Lymphocytic Leukemia | Duration of Response | NA Month |
Primary
Objective Overall Response Rate
The 1999 international response criteria (http://www.ncbi.nlm.nih.gov/pubmed/10655437#) as published by Cheson was used for the definition of target lesions and CT scans were used for response assessment. CR(complete response)/CRu(unconfirmed complete response) requires disappearance of all target lesions; PR (partial response) requires \>=50% decrease in the sum of the products of the greatest diameters; Overall Response (OR)=CR/CRu+PR.
Time frame: Up to 6 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aggressive B-cell Lymphoma | Objective Overall Response Rate | 28.1 percentage of participants |
| Follicular Lymphoma | Objective Overall Response Rate | 53.8 percentage of participants |
| Chronic Lymphocytic Leukemia | Objective Overall Response Rate | 11.1 percentage of participants |
Primary
Overall Survival
The overall survival was evaluated using the Kaplan-Meier estimator.
Time frame: Up to 6 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Aggressive B-cell Lymphoma | Overall Survival | 7.3 Month |
| Follicular Lymphoma | Overall Survival | NA Month |
| Chronic Lymphocytic Leukemia | Overall Survival | 31.5 Month |