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

NCT ID: NCT00436618

Last Updated: 2019-10-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 277 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-08-31
• Study Completion Date: 2019-10-09

Brief Summary

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.

Detailed 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.

Conditions

Leukemia; Lymphoma; Lymphoproliferative Disorder

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Relapsed aggressive non-Hodgkin lymphoma

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

Group Type: EXPERIMENTAL

Everolimus

Intervention Type: DRUG

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

Relapsed indolent non-Hodgkin lymphoma

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

Group Type: EXPERIMENTAL

Everolimus

Intervention Type: DRUG

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

Uncommon lymphomas

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.

Group Type: EXPERIMENTAL

Everolimus

Intervention Type: DRUG

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

Interventions

Everolimus

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

Intervention Type: DRUG

Other Intervention Names

Mayo abbreviation: RAD001

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thomas E. Witzig, MD

Role: STUDY_CHAIR

Mayo Clinic

Locations

Mayo Clinic Scottsdale

Scottsdale, Arizona, United States

Mayo Clinic - Jacksonville

Jacksonville, Florida, United States

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Countries

United States

References

Ghobrial IM, Gertz M, Laplant B, Camoriano J, Hayman S, Lacy M, Chuma S, Harris B, Leduc R, Rourke M, Ansell SM, Deangelo D, Dispenzieri A, Bergsagel L, Reeder C, Anderson KC, Richardson PG, Treon SP, Witzig TE. Phase II trial of the oral mammalian target of rapamycin inhibitor everolimus in relapsed or refractory Waldenstrom macroglobulinemia. J Clin Oncol. 2010 Mar 10;28(8):1408-14. doi: 10.1200/JCO.2009.24.0994. Epub 2010 Feb 8.

Reference Type: RESULT

PMID: 20142598 (View on PubMed)

Johnston PB, Inwards DJ, Colgan JP, Laplant BR, Kabat BF, Habermann TM, Micallef IN, Porrata LF, Ansell SM, Reeder CB, Roy V, Witzig TE. A Phase II trial of the oral mTOR inhibitor everolimus in relapsed Hodgkin lymphoma. Am J Hematol. 2010 May;85(5):320-4. doi: 10.1002/ajh.21664.

Reference Type: RESULT

PMID: 20229590 (View on PubMed)

Witzig TE, Reeder CB, LaPlant BR, Gupta M, Johnston PB, Micallef IN, Porrata LF, Ansell SM, Colgan JP, Jacobsen ED, Ghobrial IM, Habermann TM. A phase II trial of the oral mTOR inhibitor everolimus in relapsed aggressive lymphoma. Leukemia. 2011 Feb;25(2):341-7. doi: 10.1038/leu.2010.226. Epub 2010 Dec 7.

Reference Type: RESULT

PMID: 21135857 (View on PubMed)

Zent CS, LaPlant BR, Johnston PB, Call TG, Habermann TM, Micallef IN, Witzig TE. The treatment of recurrent/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) with everolimus results in clinical responses and mobilization of CLL cells into the circulation. Cancer. 2010 May 1;116(9):2201-7. doi: 10.1002/cncr.25005.

Reference Type: RESULT

PMID: 20166206 (View on PubMed)

Witzig TE, Reeder C, Han JJ, LaPlant B, Stenson M, Tun HW, Macon W, Ansell SM, Habermann TM, Inwards DJ, Micallef IN, Johnston PB, Porrata LF, Colgan JP, Markovic S, Nowakowski GS, Gupta M. The mTORC1 inhibitor everolimus has antitumor activity in vitro and produces tumor responses in patients with relapsed T-cell lymphoma. Blood. 2015 Jul 16;126(3):328-35. doi: 10.1182/blood-2015-02-629543. Epub 2015 Apr 28.

Reference Type: DERIVED

PMID: 25921059 (View on PubMed)

Other Identifiers

P30CA015083

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MC048G

Identifier Type: OTHER

Identifier Source: secondary_id

1042-05

Identifier Type: OTHER

Identifier Source: secondary_id

MC048G

Identifier Type: -

Identifier Source: org_study_id