NCT00436618

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
277

participants targeted

Target at P75+ for phase_2 leukemia

Timeline
Completed

Started Aug 2005

Longer than P75 for phase_2 leukemia

Geographic Reach
1 country

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 1, 2005

Completed
1.5 years until next milestone

First Submitted

Initial submission to the registry

February 15, 2007

Completed
4 days until next milestone

First Posted

Study publicly available on registry

February 19, 2007

Completed
3.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2010

Completed
2.7 years until next milestone

Results Posted

Study results publicly available

July 30, 2013

Completed
6.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

October 9, 2019

Completed
Last Updated

October 22, 2019

Status Verified

October 1, 2018

Enrollment Period

5.3 years

First QC Date

February 15, 2007

Results QC Date

May 1, 2013

Last Update Submit

October 11, 2019

Conditions

LeukemiaLymphomaLymphoproliferative Disorder

Keywords

recurrent adult Burkitt lymphomarecurrent adult Hodgkin lymphomaanaplastic large cell lymphomaangioimmunoblastic T-cell lymphomaextranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissuenodal marginal zone B-cell lymphomasplenic marginal zone lymphomasmall intestine lymphomarecurrent adult diffuse mixed cell lymphomarecurrent adult T-cell leukemia/lymphomarecurrent grade 3 follicular lymphomarecurrent marginal zone lymphomarefractory chronic lymphocytic leukemiarecurrent small lymphocytic lymphomarecurrent mycosis fungoides/Sezary syndromeadult nasal type extranodal NK/T-cell lymphomaWaldenstrom macroglobulinemiarecurrent adult diffuse large cell lymphomarecurrent adult lymphoblastic lymphomarecurrent mantle cell lymphomarecurrent grade 1 follicular lymphomarecurrent grade 2 follicular lymphomaprimary central nervous system non-Hodgkin lymphomaprimary central nervous system Hodgkin lymphomapost-transplant lymphoproliferative disorderrecurrent adult diffuse small cleaved cell lymphoma

Outcome Measures

Primary Outcomes (1)

  • Tumor Response, Defined by Disease: Chronic Lymphocytic Leukemia(CLL): Clinical Complete or Complete or Nodular Partial or Partial Remission, Waldenstrom: Complete or Partial Response, All Others: Complete or Complete Unconfirmed or Partial Response.

    CLL (subset of patients in the Relapsed Indolent Non-Hodgkin Lymphoma group): 50% decrease in peripheral blood lymphocytes, lymphadenopathy, liver/spleen size, presence/absence of constitutional symptoms; plus ≥1 of the following: ≥1500/μL polymorphonuclear leukocytes, \>100000/μL platelets, \>11.0 g/dL hemoglobin or 50% improvement for these parameters without transfusions. Waldenstrom (subset of patients in the Uncommon Lymphomas group): \>50% reduction in serum immunoglobulin M(IgM) levels (by serum protein electrophoresis (SPEP)) during any point while in this study, and no appearance of new lesions. All others: at least a 50% decrease in the sum of the products of the greatest diameters (SPD) of the six largest dominant nodes or nodal masses and no increase in the size of other nodes, liver, or spleen and splenic and hepatic nodules must regress by at least 50% in the SPD and no new sites of disease.

    5 years

Secondary Outcomes (3)

  • Overall Survival

    5 years

  • Progression-free Survival

    5 years

  • Time to Progression

    5 years

Study Arms (3)

Relapsed aggressive non-Hodgkin lymphoma

EXPERIMENTAL

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

Drug: Everolimus

Relapsed indolent non-Hodgkin lymphoma

EXPERIMENTAL

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

Drug: Everolimus

Uncommon lymphomas

EXPERIMENTAL

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.

Drug: Everolimus

Interventions

EverolimusDRUG

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

Also known as: Mayo abbreviation: RAD001
Relapsed aggressive non-Hodgkin lymphomaRelapsed indolent non-Hodgkin lymphomaUncommon lymphomas

Eligibility Criteria

Age18 Years - 120 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

Study Sites (3)

Mayo Clinic Scottsdale

Scottsdale, Arizona, 85259-5499, United States

Location

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

Related Publications (5)

  • 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.

    PMID: 20142598RESULT

  • 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.

    PMID: 20229590RESULT

  • 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.

    PMID: 21135857RESULT

  • 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.

    PMID: 20166206RESULT

  • 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.

    PMID: 25921059DERIVED

MeSH Terms

Conditions

LeukemiaLymphomaLymphoproliferative DisordersBurkitt LymphomaHodgkin DiseaseLymphoma, Large-Cell, AnaplasticImmunoblastic LymphadenopathyLymphoma, B-Cell, Marginal ZoneLymphoma, Non-HodgkinPrecursor T-Cell Lymphoblastic Leukemia-LymphomaLymphoma, FollicularLeukemia, Lymphocytic, Chronic, B-CellMycosis FungoidesSezary SyndromeLymphoma, Extranodal NK-T-CellWaldenstrom MacroglobulinemiaLymphoma, Large B-Cell, DiffusePrecursor Cell Lymphoblastic Leukemia-LymphomaLymphoma, Mantle-Cell

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsLymphoma, B-CellLymphoma, T-CellLymphadenopathyLeukemia, LymphoidLeukemia, B-CellChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsLymphoma, T-Cell, CutaneousNeoplasms, Plasma CellHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic Disorders

Intervention Hierarchy (Ancestors)

SirolimusMacrolidesLactonesOrganic Chemicals

Results Point of Contact

Title
Thomas E. Witzig M.D.
Organization
Mayo Clinic
witzig.thomas@mayo.edu
(507) 284-0527

Study Officials

  • Thomas E. Witzig, MD

    Mayo Clinic

    STUDY CHAIR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 15, 2007

First Posted

February 19, 2007

Study Start

August 1, 2005

Primary Completion

December 1, 2010

Study Completion

October 9, 2019

Last Updated

October 22, 2019

Results First Posted

July 30, 2013

Record last verified: 2018-10

Locations

US(3)