AzTrials
AzTrials

Non-Hodgkin's LymphomasPhase 1(RAD001-R)NCT01567475

The Combination of Rad001 and Rituximab In Patients With Non-hodgkin's Lymphomas

A Phase 1 study testing Everolimus and rituximab in people with Non-Hodgkin's Lymphomas, run by The Lymphoma Academic Research Organisation at 5 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This study is an open label, multicenter study with two phases: Phase I is a dose escalation study of RAD001 in combination with one injection of Rituximab 375 mg/m² per week during 4 weeks (28 days) in patients CD20 positive non-Hodgkin's lymphomas to determine the dose limiting toxicities (DLTs) and maximum… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-Hodgkin's Lymphomas
What is being tested?
Everolimus and rituximab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
5 sitesFrance
Study dates
Dec 2011to Dec 2015
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with relapsed or refractory of one of the following CD 20 positive B-cell Lymphoma:
  • 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 allowed.
Show all 15Show fewer
  • 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.

Who cannot join

  • 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 IV
Show all 22Show fewer
  • 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 C).
  • 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

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

France5 sites

  • Service des Maladies du Sang - CHRU de Lille

    Lille, 59037

  • Service Hématologie - Hôtel Dieu de NANTES

    Nantes, 44035

  • Service Hématologie - CHU Lyon Sud

    Pierre-Bénite, 69495

  • Service Hématologie - Centre Henri Becquerel

    Rouen, 76038

  • Service Hématologie - Institut Gustave Roussy

    Villejuif, 94805

Other trials in France

About this study

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

This study is an open label, multicenter study with two phases:

  • Phase I is a dose escalation study of RAD001 in combination with one injection of Rituximab 375 mg/m² per week during 4 weeks (28 days) in patients CD20 positive non-Hodgkin's lymphomas to determine the dose limiting toxicities (DLTs) and maximum tolerated dose (MTD). The purpose of the study is to assess the feasibility of the combination based on - rate of dose limiting toxicities (DLT) and PK drug-drug interaction (DDI).
  • Phase II will define the efficacy and safety profile of RAD001 and Rituximab combination at the RP2D in patients with lymphomas.
Read more

Patients with lymphomas will be treated at the RP2D established during phase I and evaluated for clinical benefit rate, comprising complete responses (CR + CRu), partial responses (PR) and stable disease (SD), and time to progression using the IWG criteria for treatment response.

Induction therapy will follow the same schedule than during the phase I study.

Maintenance therapy: Monthly cycles for up to 2 years with:

  • Daily RAD001 at the same dose than during induction therapy.
  • Rituximab infusion every other cycle at 375 mg/m2 that correspond to the usual maintenance schedule for Rituximab.

Response to therapy will be assessed between day 42 and day 49, then every two months.

Being tested
Everolimus and rituximab

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Everolimus and rituximabDrug

    One injection of Rituximab 375 mg/m2 per week during 28 days followed by one Rituximab infusion every other cycle at 375 mg/m2 associated with everolimus at 5mg or 10 mg every day or 5 mg every other day.

Study groups in NCT01567475
Study groupRoleWhat they receive
Everolimus and rituximabExperimentalNot described
Receives: Drug: Everolimus and rituximab

What is being measured

The primary outcome is the main question the study is designed to answer.

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

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

    Measured: 28 days

  2. Phase II part: Complete Response Rate (CR+CRu)

    Assessment of response will be based on the International Workshop to Standardize Response criteria for NHL (Criteria for evaluation of response in Non-Hodgkin's lymphoma Cheson,1999)

    Measured: 2 years

Secondary outcomes (4)

  1. OVERALL RESPONSE RATE

    The same disease response assessment used for complete response rate will be considered to determine the Overall Response Rate. Patient is defined as a responder if he/she has a complete response (CR/CRu) or partial response (PR) at the end of treatment. A descriptive analysis will also be performed considering as nonresponders all patients who relapsed or died during treatment phase even if they were prematurely withdrawn as responder.

    Measured: 2 years

  2. PROGRESSION-FREE SURVIVAL

    Progression-Free Survival will be measured from the date of inclusion to the date of first documented disease progression, relapse or death from any cause. Responding patients and patients who are lost to follow up will be censored at their last tumor assessment date.

    Measured: Up to 4 years

  3. OVERALL SURVIVAL

    Overall survival will be measured from the date of inclusion to the date of death from any cause. Patients who are alive at the time of analysis will be censored at the date of the last contact.

    Measured: Up to 4 years

  4. DURATION OF RESPONSE

    Duration of response will be measured from the date of first documentation of a response (CR/CRu or PR after induction or at the end of treatment) to the date of first documented evidence of progression/relapse or death from any cause. Responding patients and patients who are lost to follow up will be censored at their last tumor assessment date.

    Measured: Up to 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Mar 2012 (estimated)
  2. Study startDec 2011
  3. Primary completionJun 2013
  4. Study completionDec 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01567475
Sponsor's protocol ID
RAD001-R
Acronym
(RAD001-R)
Status last verified
Mar 2016
First submitted
26 Oct 2011
Last updated
15 Mar 2016
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Everolimus and rituximab in people with Non-Hodgkin's Lymphomas, run by The Lymphoma Academic Research Organisation at 5 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase I part: Determination of the Recommended Dose of RAD001 in combination with rituximab. (time frame: 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01567475.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2016.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in