Clinical trial NCT00290472: CCI-779 in Treating Patients With Recurrent or Refractory B-Cell Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia
Official title: A Phase II Study of CCI-779 in B-cell Lymphoma and CLL
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2006-02-13
Enrollment: 89
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: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Objective Overall Response Rate
timeFrame: Up to 6 years
measure: Duration of Response
timeFrame: Up to 6 years
measure: Overall Survival
timeFrame: Up to 6 years
Secondary outcomes:
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital
state: Illinois
city: Evanston
country: United States
facility: Evanston Hospital CCOP
state: Illinois
city: Harvey
country: United States
facility: Ingalls Memorial Hospital
state: Illinois
city: La Grange
country: United States
facility: Adventist La Grange Memorial Hospital
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Springfield
country: United States
facility: Central Illinois Hematology Oncology Center
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology Inc-Parkview
state: Indiana
city: South Bend
country: United States
facility: Northern Indiana Cancer Research Consortium
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Saint Joseph
country: United States
facility: Oncology Care Associates PLLC
state: Michigan
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
city: Milwaukee
country: United States
facility: Froedtert and the Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: University of Chicago
name: Sonali Smith
role: PRINCIPAL_INVESTIGATOR
References:
citation: Smith SM, van Besien K, Karrison T, Dancey J, McLaughlin P, Younes A, Smith S, Stiff P, Lester E, Modi S, Doyle LA, Vokes EE, Pro B. Temsirolimus has activity in non-mantle cell non-Hodgkin's lymphoma subtypes: The University of Chicago phase II consortium. J Clin Oncol. 2010 Nov 1;28(31):4740-6. doi: 10.1200/JCO.2010.29.2813. Epub 2010 Sep 13.