AzTrials
AzTrials

LeukemiaPhase 2NCT00436618

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

A Phase 2 study testing Everolimus in people with Leukemia and Lymphoma, run by Mayo Clinic at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 to 120 years
Conditions the study is for
Leukemia, Lymphoma, Lymphoproliferative Disorder
What is being tested?
Everolimus
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
277 participants
Where
3 sitesUnited States
Study dates
Aug 2005to 9 Oct 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 120 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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 locations and contacts

3 sites in 1 country.

United States3 sites

  • Mayo Clinic - Jacksonville

    Jacksonville, Florida, 32224

  • Mayo Clinic Cancer Center

    Rochester, Minnesota, 55905

  • Mayo Clinic Scottsdale

    Scottsdale, Arizona, 85259-5499

Other trials in United States

About this study

Official title: Phase II Trial of Everolimus (RAD001) in Relapsed/Refractory Lymphoma

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.

Read the 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.

Being tested
Everolimus
Keywords
recurrent adult Burkitt lymphoma, recurrent adult Hodgkin lymphoma, anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma, small intestine lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult T-cell leukemia/lymphoma, recurrent grade 3 follicular lymphoma, recurrent marginal zone lymphoma, refractory chronic lymphocytic leukemia, recurrent small lymphocytic lymphoma, recurrent mycosis fungoides/Sezary syndrome, adult nasal type extranodal NK/T-cell lymphoma, Waldenstrom macroglobulinemia, recurrent adult diffuse large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent mantle cell lymphoma
Medical subject headings
Leukemia, Lymphoma, Lymphoproliferative Disorders, Burkitt Lymphoma, Hodgkin Disease, Lymphoma, Large-Cell, Anaplastic, Immunoblastic Lymphadenopathy, Lymphoma, B-Cell, Marginal Zone

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EverolimusDrug

    Also called Mayo abbreviation: RAD001

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

Study groups in NCT00436618
Study groupRoleWhat they receive
Relapsed aggressive non-Hodgkin lymphomaExperimentalStudy 1. Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time.
Receives: Drug: Everolimus
Relapsed indolent non-Hodgkin lymphomaExperimentalStudy 2. Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time.
Receives: Drug: Everolimus
Uncommon lymphomasExperimentalStudy 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.
Receives: Drug: Everolimus

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 5 years

Secondary outcomes (3)

  1. Overall Survival

    The overall survival or survival time is defined as the time from registration to death due to any cause. The distribution of overall survival was estimated using the method of Kaplan-Meier.

    Measured: 5 years

  2. Progression-free Survival

    Progression-free survival is defined as the time from registration to the time of progression or death due to any cause. Progression-free survival was estimated using the method of Kaplan-Meier.

    Progression is defined as the following:

    CLL (subset of patients in the Relapsed Indolent Non-Hodgkin Lymphoma group): >=50% increase in nodes from nadir or >=50% increase in liver/spleen size from nadir.

    Waldenstrom (subset of patients in the Uncommon Lymphomas group): >50% lymph node increase in SPD of > 1 node or new nodes, or >50% liver/spleen size increase, or > 25% IgM (by SPEP) increase, or lymphocyte morphology transformation to a more aggressive histology.

    All Others: New lesions or >=50% lymph nodes.

    Measured: 5 years

  3. Time to Progression

    The time to progression is defined as the time from registration to the time of progression. The distribution of time to progression was estimated using the method of Kaplan-Meier.

    Measured: 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Feb 2007 (estimated)
  2. Study startAug 2005
  3. Primary completionDec 2010
  4. Study completion9 Oct 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
277 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00436618
Sponsor's protocol ID
MC048G
Other IDs
P30CA015083, MC048G, 1042-05
Status last verified
Oct 2018
First submitted
15 Feb 2007
Last updated
22 Oct 2019
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 20142598

  • 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.

    PubMed 20229590

  • 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.

    PubMed 21135857

  • 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.

    PubMed 20166206

  • 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.

    PubMed 25921059

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Everolimus in people with Leukemia and Lymphoma, run by Mayo Clinic at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Jul 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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. (time frame: 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00436618, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2019.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in