Everolimus in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier:
NCT00516412
First received: August 14, 2007
Last updated: August 7, 2012
Last verified: August 2012

August 14, 2007
August 7, 2012
August 2007
January 2010   (final data collection date for primary outcome measure)
Evaluation of the efficacy and tolerability of everolimus [ Time Frame: Until treatment ends ] [ Designated as safety issue: No ]
Objective response
Complete list of historical versions of study NCT00516412 on ClinicalTrials.gov Archive Site
  • Evaluation of the efficacy of everolimus to induce molecular remission in patients treated with this regimen. [ Time Frame: Until treament ends ] [ Designated as safety issue: No ]
  • Investigation of immunoglobulin heavy chain variable gene somatic hypermutations [ Time Frame: Until treatment ends ] [ Designated as safety issue: No ]
    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. [ Time Frame: Until treatment ends ] [ Designated as safety issue: No ]
  • Adverse reactions
  • Time to progression
  • Response duration
  • Time to treatment failure
  • Molecular response (PCR status after courses 3 and 6) in patients who test PCR-positive at baseline
Not Provided
Not Provided
 
Everolimus in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma
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

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.

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.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Lymphoma
  • Drug: everolimus
    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.
  • Genetic: molecular response by PCR
    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
Active Comparator: Everolimus
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.
Interventions:
  • Drug: everolimus
  • Genetic: molecular response by PCR
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
35
August 2012
January 2010   (final data collection date for primary outcome measure)

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)
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
France,   Italy,   Switzerland
 
NCT00516412
SAKK 36/06, EU-20749, EUDRACT-2007-001108-19
Yes
Swiss Group for Clinical Cancer Research
Swiss Group for Clinical Cancer Research
Not Provided
Principal Investigator: Christoph Renner, MD UniversitaetsSpital Zuerich
Swiss Group for Clinical Cancer Research
August 2012

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