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

National Cancer Institute (NCI)

Status and phase: Completed; Phase 2

Conditions: Waldenström Macroglobulinemia; Malignant Neoplasm; Recurrent Small Lymphocytic Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Splenic Marginal Zone Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; B-cell Chronic Lymphocytic Leukemia; Recurrent Adult Diffuse Mixed Cell Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Refractory Chronic Lymphocytic Leukemia; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma

Treatments: Drug: temsirolimus

Study type: Interventional

Funder types: NIH

Identifiers

NCT00290472

CDR0000365314

NCI-2009-00047 (Registry Identifier)

12983A

P30CA014599 (U.S. NIH Grant/Contract)

N01CM62202 (U.S. NIH Grant/Contract)

N01CM62201 (U.S. NIH Grant/Contract)

6199 (Other Identifier)

NCI-6199

Details and patient eligibility

About

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.

Full 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.

Enrollment: 89 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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)

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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89 participants in 1 patient group

Arm I

Experimental group

Description:

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.

Treatment:

Drug: temsirolimus