Everolimus in Treating Patients With Lymphoma That Has Relapsed or Not Responded to Previous Treatment

Mayo Clinic

Status and phase: Completed; Phase 2

Conditions: Lymphoproliferative Disorder; Lymphoma; Leukemia

Treatments: Drug: Everolimus

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00436618

P30CA015083 (U.S. NIH Grant/Contract)

1042-05 (Other Identifier)

MC048G (Other Identifier)

Details and patient eligibility

About

RATIONALE: Everolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer.

PURPOSE: This phase II trial is studying the side effects and how well everolimus works in treating patients with lymphoma that has relapsed or not responded to previous treatment.

Full description

OBJECTIVES:

Primary

• Assess the tumor response in patients with relapsed or refractory indolent non-Hodgkin lymphoma (closed to accrual as of 8/18/08), aggressive non-Hodgkin's lymphoma (closed to accrual as of 2/7/08 except for diffuse large B cell lymphoma, grade III follicular lymphoma, or transformed lymphoma), or uncommon lymphoma (closed to accrual as of 9/2/08), including Hodgkin's lymphoma, treated with everolimus.

Secondary

• Evaluate overall survival, progression-free survival, and time to disease progression in patients treated with this drug.

OUTLINE: This is a multicenter study. Patients are stratified according to histology (aggressive lymphoma [closed to accrual as of 2/7/08 except for diffuse large B cell lymphoma, grade III follicular lymphoma, or transformed lymphoma] vs indolent lymphoma [closed to accrual as of 8/18/08] vs uncommon lymphoma [closed to accrual as of 9/2/08]).

Patient receive oral everolimus daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo blood and tissue collection at baseline and periodically during study treatment for translational research studies. Blood and tissue samples are analyzed for biomarkers to study the effect of everolimus on lymphoma.

After completion of study treatment, patients are followed periodically for up to 5 years.

Enrollment: 277 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Biopsy-proven* relapsed or refractory lymphoma, including the following:

  • Aggressive lymphoma (closed to accrual as of 2/7/08 except for diffuse large B cell lymphoma, grade III follicular lymphoma, or transformed lymphoma)

    • Transformed lymphoma
    • Diffuse large B-cell lymphoma
    • Mantle cell lymphoma
    • Grade 3 follicular lymphoma
    • Precursor B-cell lymphoblastic leukemia/lymphoma
    • Mediastinal (thymic) large B-cell lymphoma
    • Burkitt's lymphoma/leukemia
    • Precursor T-cell lymphoblastic leukemia/lymphoma
    • Primary cutaneous anaplastic large cell lymphoma
    • Primary systemic type anaplastic large cell lymphoma

  • Indolent lymphoma (closed to accrual as of 8/18/08)

    • Small lymphocytic lymphoma/chronic lymphocytic leukemia
    • Grade 1 or 2 follicular lymphoma
    • Extranodal marginal zone B-cell lymphoma of MALT type
    • Nodal marginal zone B-cell lymphoma
    • Splenic marginal zone B-cell lymphoma

  • Uncommon lymphoma (closed to accrual as of 9/2/08)

    • Unspecified peripheral T-cell lymphoma
    • Anaplastic large cell lymphoma (T and null cell type)
    • Lymphoplasmacytic lymphoma (Waldenstrom's macroglobulinemia)
    • Central Nervous System (CNS) lymphoma
    • Post-transplant lymphoproliferative disorder
    • Mycosis fungoides/Sezary syndrome
    • Hodgkin's lymphoma
    • Primary effusion lymphoma
    • Blastic Natural Killer(NK)-cell lymphoma
    • Adult T-cell leukemia/lymphoma
    • Nasal type extranodal NK/T-cell lymphoma
    • Enteropathy type T-cell lymphoma
    • Hepatosplenic T-cell lymphoma
    • Subcutaneous panniculitis-like T-cell lymphoma
    • Angioimmunoblastic T-cell lymphoma

NOTE: *Biopsies performed < 6 months prior to study entry are allowed; biopsy-proven CNS lymphoma (at any time) does not require a re-biopsy in order to be eligible for this study

• Previously treated disease

  • Patients with aggressive lymphoma (closed to accrual as of 8/24/07) OR Hodgkin's lymphoma must have received or be ineligible for potentially curative therapy, including stem cell transplantation

• Measurable disease** by CT scan or MRI, defined by 1 of the following:

  • At least 1 unidimensionally measurable lesion > 2 cm in diameter

    • Skin lesions may be used if they meet this criterion and are photographed with a ruler

  • More than 5,000/mm³ tumor cells in the blood

NOTE: **For patients with lymphoplasmacytic lymphoma without measurable lymphadenopathy, measurable disease may be defined by bone marrow lymphoplasmacytosis with > 10% lymphoplasmacytic cells or aggregates, sheets, lymphocytes, plasma cells, or lymphoplasmacytic cells on bone marrow biopsy AND quantitative Immunoglobulin M(IgM) monoclonal protein > 1,000 mg/dL

PATIENT CHARACTERISTICS:

• Eastern Cooperative Oncology Group(ECOG) performance status 0-2
• Life expectancy > 3 months
• Absolute neutrophil count ≥ 1,000/mm³
• Platelet count ≥ 75,000/mm³
• Hemoglobin ≥ 8 g/dL
• Total bilirubin ≤ 2 times upper limit of normal (ULN) OR direct bilirubin ≤ 1.5 times ULN
• aspartate aminotransferase(AST) ≤ 3 times ULN (5 times ULN if liver involvement is present)
• Creatinine ≤ 2 times ULN
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Willing to provide blood samples and portion of bone marrow aspirate and biopsy during study participation
• Able to swallow intact study medication tablets
• No other life-threatening illness (unrelated to tumor)
• No serious non-malignant disease (e.g., active infection or other condition) that, in the opinion of the investigator, would preclude study participation
• No other active malignancy requiring treatment or that would preclude study participation
• No known HIV positivity

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• At least 3 weeks since prior myelosuppressive chemotherapy or biologic therapy (unless the patient has recovered from the nadir of the previous treatment)

• More than 3 weeks since prior radiotherapy (unless the acute side effects associated with therapy are resolved)

• Concurrent stable (i.e., not increased within the past month) chronic doses of corticosteroids, with a maximum dose of 20 mg of prednisone per day, is allowed if prescribed for disorders other than lymphoma (e.g., rheumatoid arthritis, polymyalgia rheumatica, adrenal insufficiency, or asthma)

  • Non-escalating doses of steroids at the lowest possible dosing level are allowed for CNS lymphoma

• No other concurrent investigational ancillary therapy

• No other concurrent chemotherapy, immunotherapy, or radiotherapy

• No concurrent participation in any other clinical trial involving a pharmacologic agent (e.g., drugs, biologics, immunotherapy, or gene therapy) for symptom control or therapeutic intent

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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277 participants in 3 patient groups

Relapsed aggressive non-Hodgkin lymphoma

Experimental group

Description:

Study 1. Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time.

Treatment:

Drug: Everolimus

Relapsed indolent non-Hodgkin lymphoma

Experimental group

Description:

Study 2. Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time.

Treatment:

Drug: Everolimus

Uncommon lymphomas

Experimental group

Description:

Study 3. Includes Hodgkin's lymphomas. Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time.

Treatment:

Drug: Everolimus