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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00436618
First received: February 15, 2007
Last updated: July 24, 2013
Last verified: July 2013

February 15, 2007
July 24, 2013
August 2005
December 2010   (final data collection date for 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 ] [ Designated as safety issue: No ]

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.

Confirmed response, defined as complete response (CR), CR unconfirmed, or partial response (PR)
Complete list of historical versions of study NCT00436618 on ClinicalTrials.gov Archive Site
  • Overall Survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    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.
  • Progression-free Survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]

    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.

  • Time to Progression [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    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.
  • Overall survival
  • Progression-free survival
  • Duration of response (CR or PR)
  • Correlation of molecular effects of everolimus on proteins downstream of MTOR, such as phospho-S6 and cyclin D1, with response to therapy
Not Provided
Not Provided
 
Everolimus in Treating Patients With Lymphoma That Has Relapsed or Not Responded to Previous Treatment
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.

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.

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Leukemia
  • Lymphoma
  • Lymphoproliferative Disorder
Drug: Everolimus
Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time.
Other Name: Mayo abbreviation: RAD001
  • Experimental: 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.
    Intervention: Drug: Everolimus
  • Experimental: 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.
    Intervention: Drug: Everolimus
  • Experimental: 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.
    Intervention: Drug: Everolimus

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
277
Not Provided
December 2010   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00436618
MC048G, P30CA015083, MC048G, 1042-05
Yes
Thomas E. Witzig, Mayo Clinic Cancer Center
Mayo Clinic
National Cancer Institute (NCI)
Study Chair: Thomas E. Witzig, MD Mayo Clinic
Mayo Clinic
July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP