Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Everolimus in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Biomarker/Laboratory analysis, Treatment Active 18 and over Other SWS-SAKK-36/06 SAKK 36/06, EU-20749, EUDRACT-2007-001108-19, NCT00516412

Objectives

Primary

1. Evaluation of the efficacy and tolerability of everolimus in patients with relapsed or therapy-resistant mantle cell lymphoma.

Secondary

1. Evaluation of the efficacy of everolimus to induce molecular remission in patients treated with this regimen.
2. 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.
3. Evaluation of a putative impact of Ig-V_H on clinical outcome.

Entry 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 meningeosis)



• 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])

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)

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)

Expected Enrollment

Outcomes

Objective response

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

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.

Trial Contact Information

Trial Lead Organizations

Swiss Group for Clinical Cancer Research

Christoph Renner, MD, Principal investigator		Ph: 41-44-255-8902

France
	Grenoble
	CHU de Grenoble - Hopital de la Tronche
		Contact Person	Ph:  33-47-676-7575
	Pessac
	Hopital Haut Leveque
		Contact Person	Ph:  33-55-765-6511
	Tours
	Centre Hospitalier Universitaire Bretonneau de Tours
		Contact Person	Ph:  32-24-747-3712
	Villejuif
	Institut Gustave Roussy
		Contact Person	Ph:  33-14-211-4321
Italy
	Bologna
	University of Bologna Medical School
		Contact Person	Ph:  39-51-636-3680
	Milan
	European Institute of Oncology
		Contact Person	Ph:  39-02-5748-9538
Switzerland
	Aarau
	Hirslanden Klinik Aarau
		Contact Person	Ph:  41-62-836-7833
	Kantonspital Aarau
		Contact Person	Ph:  41-62-838-6053
	Baden
	Kantonsspital Baden
		Contact Person	Ph:  41-56-486-2511
	Basel
	Universitaetsspital-Basel
		Contact Person	Ph:  41-61-925-2710
	Bern
	Inselspital Bern
		Contact Person	Ph:  41-31-632-8430
	Chur
	Kantonsspital Graubuenden
		Contact Person	Ph:  41-81-256-7170
	Lausanne
	Centre Hospitalier Universitaire Vaudois
		Contact Person	Ph:  41-21-314-0166
	Olten
	Kantonsspital Olten
		Contact Person	Ph:  41-62-311-4241
	St. Gallen
	Kantonsspital - St. Gallen
		Contact Person	Ph:  41-71-494-1066
	Thonex-Geneve
	Hopitaux Universitaires de Geneve
		Contact Person	Ph:  41-22-372-9862
	Winterthur
	Kantonsspital Winterthur
		Contact Person	Ph:  41-52-266-3640
	Zurich
	City Hospital Triemli
		Contact Person	Ph:  41-44-466-1268
	Klinik Hirslanden
		Contact Person	Ph:  41-44-387-3780
	UniversitaetsSpital Zuerich
		Contact Person	Ph:  41-44-255-8902

Registry Information
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
Trial Start Date		2007-08-20
Trial Completion Date		2009-12-31 (estimated)
Registered in ClinicalTrials.gov		NCT00516412
Date Submitted to PDQ		2007-07-18
Information Last Verified		2008-11-30

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