CCI-779 in Treating Patients With Recurrent or Refractory B-Cell Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia

Phase 2

Completed

Conditions: B-cell Chronic Lymphocytic Leukemia
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Recurrent Marginal Zone Lymphoma
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

Interventions: Drug: temsirolimus

Registration Number: NCT00290472

Lead Sponsor: National Cancer Institute (NCI)

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 89

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)

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm I	temsirolimus	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.

Primary Outcome Measures

Name	Time	Method
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.

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (13): Decatur Memorial Hospital
🇺🇸
Decatur, Illinois, United States
Loyola University Medical Center
🇺🇸
Maywood, Illinois, United States
Fort Wayne Medical Oncology and Hematology Inc-Parkview
🇺🇸
Fort Wayne, Indiana, United States
M D Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Evanston Hospital CCOP
🇺🇸
Evanston, Illinois, United States
Ingalls Memorial Hospital
🇺🇸
Harvey, Illinois, United States
Adventist La Grange Memorial Hospital
🇺🇸
La Grange, Illinois, United States
Oncology Care Associates PLLC
🇺🇸
Saint Joseph, Michigan, United States
University of Chicago
🇺🇸
Chicago, Illinois, United States
University of Iowa
🇺🇸
Iowa City, Iowa, United States
Central Illinois Hematology Oncology Center
🇺🇸
Springfield, Illinois, United States
Northern Indiana Cancer Research Consortium
🇺🇸
South Bend, Indiana, United States
Froedtert and the Medical College of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States