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A Phase I/II Study Investigating the Combination of RAD001 and Rituximab in Patients With Non-Hodgkin's Lymphomas

Phase 1/Phase 2
18 Years
Open (Enrolling)
Non-Hodgkin's Lymphomas

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Trial Information

A Phase I/II Study Investigating the Combination of RAD001 and Rituximab in Patients With Non-Hodgkin's Lymphomas

Inclusion Criteria:

- Patients with relapsed or refractory of one of the following CD 20 positive B-cell

- Mantle cell, Marginal zone, lymphocytic, follicular lymphoma

- Histological transformation from low grade to high grade

- Must have had at least one previous chemotherapy regimen and not more than 5 previous
chemotherapy regimens.

- Disease is measurable: existence of a bidimensional lesion greater than 2 cm in its
longer diameter or malignant lymphocytosis greater than 5000 x 109/L

- Recovery from any non-hematological toxicity derived from previous treatments. The
presence of alopecia and NCI-CTC grade < 2 symptomatic peripheral neuropathy is

- Age ≥18 years old;

- Eastern Co-operative Oncology Group (ECOG) performance status 0-1;

- Adequate liver and renal function, defined by total bilirubin ≤2.5 x institutional
upper limit of normal (ULN) or ≤5 x ULN if liver is involved by malignancy as judged
by the investigator (explanation must be provided) and creatinine ≤ 221 μmol/L ;

- Fasting serum cholesterol ≤7.75 mmol/L AND fasting triglycerides ≤ 2.5 x ULN. NOTE:
In case one or both of these thresholds are exceeded, the patient can only be
included after initiation of appropriate lipid lowering medication.

- Adequate bone marrow function, defined by absolute neutrophil count (ANC) ≥1000/mm3
and platelet count ≥100,000/mm3, unless due to disease;

- At least 3 weeks since previous chemotherapy, biological therapy, radiation therapy,
major surgery, or other investigational cancer therapy that is considered
disease-directed and have recovered from prior toxicities to Grade 0-1;

- All men of reproductive potential and women† of child-bearing potential (WOCBP) must
agree to practice effective contraception during the entire study period and for one
month after the last study treatment, unless documentation of infertility exists.

† A woman patient is considered to have childbearing potential unless she meets at
least one of the following criteria 1) Age > 50 years and naturally amenorrhoeic for
> 1 year (amenorrhoea following cancer therapy does not rule out childbearing
potential); or 2) Premature ovarian failure confirmed by a specialist gynaecologist
or 3) Previous bilateral salpingo-oophorectomy, or hysterectomy, or 4) XY genotype,
turner syndrome, uterine agenesis.

- Able to understand and willingness to sign the informed consent form.

Exclusion Criteria:

- Uncontrolled clinically significant inter-current illness including, but not limited
to, ongoing to active infection, symptomatic congestive heart failure, unstable
angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that
would limit compliance with study requirements. Patients receiving antibiotics for
infections that are under control may be included in the study;

- Impairment of gastrointestinal function or gastrointestinal disease that may
significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled
nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)

- Patients receiving chronic, systemic treatment with corticosteroids (at a dose
equivalent or greater than 20 mg prednisone per day) or another immunosuppressive
agent. Topical or inhaled corticosteroids are allowed.

- Patients should not receive immunization with attenuated live vaccines within one
week of study entry or during study period. Close contact with those who have
received attenuated live vaccines should be avoided during treatment with everolimus.
Examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral
polio, BCG, yellow fever, varicella and TY21a typhoid vaccines.

- Patients who have any severe and/or uncontrolled medical conditions or other
conditions that could affect their participation in the study such as:

- symptomatic congestive heart failure of New York heart Association Class III or

- unstable angina pectoris, symptomatic congestive heart failure, myocardial
infarction within 6 months of start of study drug, serious uncontrolled cardiac
arrhythmia or any other clinically significant cardiac disease

- severely impaired lung function as defined as spirometry and DLCO that is 50% of
the normal predicted value and/or 02 saturation that is 88% or less at rest on
room air

- uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN (Note:
Optimal glycemic control should be achieved before starting trial therapy.)

- active (acute or chronic) or uncontrolled severe infections

- liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class

- Leptomeningeal or uncontrolled CNS localization

- Concurrent malignancy, except patients with early stage squamous cell carcinoma of
the skin, basal cell carcinoma of the skin, localized prostate cancer, or cervical
intraepithelial neoplasia;

- Treatment with any other investigational drugs within the preceding 4 weeks

- Known HIV-positive (since such patients are at increased risk of lethal infections
when treated with potentially marrow-suppressive therapy);

- Known active hepatitis A, B, or C, or history of hepatitis A, B or C;

- Women who are pregnant or lactating

- Male patient whose sexual partner(s) are WOCBP who are not willing to use adequate
contraception, during the study and for 8 weeks after the end of treatment

- Patients who have received prior treatment with an mTOR inhibitor (e.g., sirolimus,
temsirolimus, everolimus).

- Patients with a known hypersensitivity to everolimus or other rapamycin (e.g.,
sirolimus, temsirolimus) or to its excipients

- History of noncompliance to medical regimen

- Patients unwilling to or unable to comply with the protocol

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Phase I part: Determination of the Recommended Dose of RAD001 in combination with rituximab.

Outcome Description:

Determination of recommended dose will be based on safety parameters and particularly on incidence of DLTs .

Outcome Time Frame:

28 days

Safety Issue:


Principal Investigator

Vincent RIBRAG, Doctor

Investigator Role:

Principal Investigator

Investigator Affiliation:

Service Hématologie, Institut Gustave Roussy


France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Study ID:




Start Date:

December 2011

Completion Date:

July 2014

Related Keywords:

  • Non-Hodgkin's Lymphomas
  • Lymphoma
  • Lymphoma, Non-Hodgkin