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Everolimus in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma

Primary Purpose

Lymphoma

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
everolimus
molecular response by PCR
Sponsored by
Swiss Group for Clinical Cancer Research
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring contiguous stage II mantle cell lymphoma, noncontiguous stage II mantle cell lymphoma, recurrent mantle cell lymphoma, stage I mantle cell lymphoma, stage III mantle cell lymphoma, stage IV mantle cell lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS:

Inclusion criteria:

  • Histologically or cytologically confirmed relapsed or chemotherapy/immunotherapy-resistant mantle cell lymphoma

    • No more than 3 lines of prior systemic treatment
  • At least one measurable lesion ≥ 15 mm in its greatest transverse diameter by CT scan

Exclusion criteria:

  • Presence or history of CNS disease (either CNS lymphoma or lymphomatous meningosis)
  • Newly diagnosed mantle cell lymphoma
  • Patients suitable for intensive treatment (e.g., hyperfractionated cyclophosphamide, vincristine, doxorubicin hydrochloride and dexamethasone with high-dose methotrexate and cytarabine [HyperCVAD])

PATIENT CHARACTERISTICS:

Inclusion criteria:

  • WHO performance status ≤ 2
  • Creatinine clearance ≥ 30mL/min
  • Bilirubin ≤ 2 times upper limit of normal (ULN)
  • Alkaline phosphatase ≤ 2 times ULN
  • AST and ALT ≤ 2 times ULN
  • Neutrophils ≥ 1,500/mm³ (≥ 1,000/mm³ with marrow infiltration)
  • Thrombocytes ≥ 100,000/mm³ (≥ 75,000/mm³ in case of bone marrow infiltration)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 12 months after study participation

Exclusion criteria:

  • Prior or concurrent hematological malignancies

    • Patients with prior solid organ tumors that required no treatment over the last 5 years and are currently free of disease are eligible

  • Cardiovascular disease including any of the following:

    • NYHA class III or IV congestive heart failure
    • Unstable angina pectoris
    • Significant arrhythmia or arrhythmia requiring chronic treatment
    • Myocardial infarction in the last 3 months

  • Serious underlying medical condition which could impair the ability of the patient to participate in the trial including any of the following:

    • Uncontrolled diabetes mellitus
    • Gastric ulcers
    • Active autoimmune disease
    • Ongoing infection (e.g., HIV or hepatitis)

PRIOR CONCURRENT THERAPY:

Exclusion criteria:

  • Prior radiation where the indicator lesion(s) are in the irradiated field
  • Prior organ transplantation
  • Participation in another clinical trial within 30 days prior to study entry
  • Concurrent anticancer drugs/treatments or experimental medications
  • Other concurrent investigational therapy
  • Other concurrent chemotherapy, immunotherapy, or radiotherapy (including palliative radiotherapy)

Sites / Locations

  • CHU de Grenoble - Hopital de la Tronche
  • Hopital Haut Leveque
  • Centre Hospitalier Universitaire Bretonneau de Tours
  • Institut Gustave Roussy
  • University of Bologna Medical School
  • European Institute of Oncology
  • Hirslanden Klinik Aarau
  • Kantonsspital Baden
  • Universitaetsspital-Basel
  • Istituto Oncologico della Svizzera Italiana
  • Inselspital Bern
  • Kantonsspital Graubuenden
  • Centre Hospitalier Universitaire Vaudois
  • Kantonsspital Olten
  • Kantonsspital - St. Gallen
  • Hopitaux Universitaires de Geneve
  • Kantonsspital Winterthur
  • Onkozentrum - Klinik im Park
  • Klinik Hirslanden
  • City Hospital Triemli
  • UniversitaetsSpital Zuerich

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Everolimus

Arm Description

Patients receive oral everolimus once daily on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Evaluation of the efficacy and tolerability of everolimus

Secondary Outcome Measures

Evaluation of the efficacy of everolimus to induce molecular remission in patients treated with this regimen.
Investigation of immunoglobulin heavy chain variable gene somatic hypermutations
Investigation of immunoglobulin heavy chain variable gene somatic hypermutations (Ig-V_H) in classical mantle cell lymphoma as compared to blastoid mantle cell lymphoma, in particular in regard to their frequency, mutation distribution pattern (antigen selected vs. at random), and the individually involved Ig-V_H families.
Evaluation of a putative impact of Ig-V_H on clinical outcome.

Full Information

First Posted
August 14, 2007
Last Updated
September 28, 2015
Sponsor
Swiss Group for Clinical Cancer Research
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1. Study Identification

Unique Protocol Identification Number
NCT00516412
Brief Title
Everolimus in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma
Official Title
Master Protocol for Mantle Cell Lymphoma A Multicenter Phase II Trial Testing Everolimus (RAD001) for the Treatment of Patients With Relapsed or Therapy Resistant Mantle Cell Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
September 2015
Overall Recruitment Status
Completed
Study Start Date
August 2007 (undefined)
Primary Completion Date
January 2010 (Actual)
Study Completion Date
August 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Swiss Group for Clinical Cancer Research

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
RATIONALE: Everolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase II trial is studying how well everolimus works in treating patients with relapsed or refractory mantle cell lymphoma.
Detailed Description
OBJECTIVES: Primary Evaluation of the efficacy and tolerability of everolimus in patients with relapsed or therapy-resistant mantle cell lymphoma. Secondary Evaluation of the efficacy of everolimus to induce molecular remission in patients treated with this regimen. Investigation of immunoglobulin heavy chain variable gene somatic hypermutations (Ig-V_H) in classical mantle cell lymphoma as compared to blastoid mantle cell lymphoma, in particular in regard to their frequency, mutation distribution pattern (antigen selected vs. at random), and the individually involved Ig-V_H families. Evaluation of a putative impact of Ig-V_H on clinical outcome. OUTLINE: This is a multicenter study. Patients receive oral everolimus once daily on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Bone marrow and peripheral blood samples are collected periodically and analyzed for molecular response by PCR. Molecular studies are also performed on DNA level formalin-fixed paraffin-embedded tissue samples. After completion of study treatment, patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually for 3 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma
Keywords
contiguous stage II mantle cell lymphoma, noncontiguous stage II mantle cell lymphoma, recurrent mantle cell lymphoma, stage I mantle cell lymphoma, stage III mantle cell lymphoma, stage IV mantle cell lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
35 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Everolimus
Arm Type
Experimental
Arm Description
Patients receive oral everolimus once daily on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
everolimus
Other Intervention Name(s)
RAD001
Intervention Description
Patients receive oral everolimus once daily on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Intervention Type
Genetic
Intervention Name(s)
molecular response by PCR
Intervention Description
Bone marrow and peripheral blood samples are collected periodically and analyzed for molecular response by PCR. Molecular studies are also performed on DNA level formalin-fixed paraffin-embedded tissue
Primary Outcome Measure Information:
Title
Evaluation of the efficacy and tolerability of everolimus
Time Frame
Until treatment ends
Secondary Outcome Measure Information:
Title
Evaluation of the efficacy of everolimus to induce molecular remission in patients treated with this regimen.
Time Frame
Until treament ends
Title
Investigation of immunoglobulin heavy chain variable gene somatic hypermutations
Description
Investigation of immunoglobulin heavy chain variable gene somatic hypermutations (Ig-V_H) in classical mantle cell lymphoma as compared to blastoid mantle cell lymphoma, in particular in regard to their frequency, mutation distribution pattern (antigen selected vs. at random), and the individually involved Ig-V_H families.
Time Frame
Until treatment ends
Title
Evaluation of a putative impact of Ig-V_H on clinical outcome.
Time Frame
Until treatment ends

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Inclusion criteria: Histologically or cytologically confirmed relapsed or chemotherapy/immunotherapy-resistant mantle cell lymphoma No more than 3 lines of prior systemic treatment At least one measurable lesion ≥ 15 mm in its greatest transverse diameter by CT scan Exclusion criteria: Presence or history of CNS disease (either CNS lymphoma or lymphomatous meningosis) Newly diagnosed mantle cell lymphoma Patients suitable for intensive treatment (e.g., hyperfractionated cyclophosphamide, vincristine, doxorubicin hydrochloride and dexamethasone with high-dose methotrexate and cytarabine [HyperCVAD]) PATIENT CHARACTERISTICS: Inclusion criteria: WHO performance status ≤ 2 Creatinine clearance ≥ 30mL/min Bilirubin ≤ 2 times upper limit of normal (ULN) Alkaline phosphatase ≤ 2 times ULN AST and ALT ≤ 2 times ULN Neutrophils ≥ 1,500/mm³ (≥ 1,000/mm³ with marrow infiltration) Thrombocytes ≥ 100,000/mm³ (≥ 75,000/mm³ in case of bone marrow infiltration) Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 12 months after study participation Exclusion criteria: Prior or concurrent hematological malignancies Patients with prior solid organ tumors that required no treatment over the last 5 years and are currently free of disease are eligible Cardiovascular disease including any of the following: NYHA class III or IV congestive heart failure Unstable angina pectoris Significant arrhythmia or arrhythmia requiring chronic treatment Myocardial infarction in the last 3 months Serious underlying medical condition which could impair the ability of the patient to participate in the trial including any of the following: Uncontrolled diabetes mellitus Gastric ulcers Active autoimmune disease Ongoing infection (e.g., HIV or hepatitis) PRIOR CONCURRENT THERAPY: Exclusion criteria: Prior radiation where the indicator lesion(s) are in the irradiated field Prior organ transplantation Participation in another clinical trial within 30 days prior to study entry Concurrent anticancer drugs/treatments or experimental medications Other concurrent investigational therapy Other concurrent chemotherapy, immunotherapy, or radiotherapy (including palliative radiotherapy)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christoph Renner, MD
Organizational Affiliation
UniversitaetsSpital Zuerich
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU de Grenoble - Hopital de la Tronche
City
Grenoble
ZIP/Postal Code
38043
Country
France
Facility Name
Hopital Haut Leveque
City
Pessac
ZIP/Postal Code
33604
Country
France
Facility Name
Centre Hospitalier Universitaire Bretonneau de Tours
City
Tours
ZIP/Postal Code
37044
Country
France
Facility Name
Institut Gustave Roussy
City
Villejuif
ZIP/Postal Code
F-94805
Country
France
Facility Name
University of Bologna Medical School
City
Bologna
ZIP/Postal Code
40138
Country
Italy
Facility Name
European Institute of Oncology
City
Milan
ZIP/Postal Code
20141
Country
Italy
Facility Name
Hirslanden Klinik Aarau
City
Aarau
ZIP/Postal Code
CH-5001
Country
Switzerland
Facility Name
Kantonsspital Baden
City
Baden
ZIP/Postal Code
CH-5404
Country
Switzerland
Facility Name
Universitaetsspital-Basel
City
Basel
ZIP/Postal Code
CH-4031
Country
Switzerland
Facility Name
Istituto Oncologico della Svizzera Italiana
City
Bellinzona
ZIP/Postal Code
6500
Country
Switzerland
Facility Name
Inselspital Bern
City
Bern
ZIP/Postal Code
CH-3010
Country
Switzerland
Facility Name
Kantonsspital Graubuenden
City
Chur
ZIP/Postal Code
CH-7000
Country
Switzerland
Facility Name
Centre Hospitalier Universitaire Vaudois
City
Lausanne
ZIP/Postal Code
CH-1011
Country
Switzerland
Facility Name
Kantonsspital Olten
City
Olten
ZIP/Postal Code
CH-4600
Country
Switzerland
Facility Name
Kantonsspital - St. Gallen
City
St. Gallen
ZIP/Postal Code
CH-9007
Country
Switzerland
Facility Name
Hopitaux Universitaires de Geneve
City
Thonex-Geneve
ZIP/Postal Code
CH-1226
Country
Switzerland
Facility Name
Kantonsspital Winterthur
City
Winterthur
ZIP/Postal Code
CH-8400
Country
Switzerland
Facility Name
Onkozentrum - Klinik im Park
City
Zurich
ZIP/Postal Code
8002
Country
Switzerland
Facility Name
Klinik Hirslanden
City
Zurich
ZIP/Postal Code
CH-8032
Country
Switzerland
Facility Name
City Hospital Triemli
City
Zurich
ZIP/Postal Code
CH-8063
Country
Switzerland
Facility Name
UniversitaetsSpital Zuerich
City
Zurich
ZIP/Postal Code
CH-8091
Country
Switzerland

12. IPD Sharing Statement

Citations:
PubMed Identifier
22315486
Citation
Renner C, Zinzani PL, Gressin R, Klingbiel D, Dietrich PY, Hitz F, Bargetzi M, Mingrone W, Martinelli G, Trojan A, Bouabdallah K, Lohri A, Gyan E, Biaggi C, Cogliatti S, Bertoni F, Ghielmini M, Brauchli P, Ketterer N; Swiss SAKK and French GOELAMS group from European Mantle Cell Lymphoma Network. A multicenter phase II trial (SAKK 36/06) of single-agent everolimus (RAD001) in patients with relapsed or refractory mantle cell lymphoma. Haematologica. 2012 Jul;97(7):1085-91. doi: 10.3324/haematol.2011.053173. Epub 2012 Feb 7.
Results Reference
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Everolimus in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma

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