Non-Hodgkin LymphomaPhase 2R2NCT01939327
Safety and Efficacy of Revlimid® (Lenalidomide) With Mabthera® (Rituximab) in Non-Hodgkin's Lymphoma
A Phase 2 study testing Lenalidomide/Rituximab in people with Non-Hodgkin Lymphoma, run by Institut Paoli-Calmettes at 1 site in France.
Trial summary
The incidence of non-Hodgkin's lymphoma (NHL) is steadily increasing worldwide. At present, it is the sixth most commonly diagnosed cancer in France, with 10 000 estimated new cases and 5200 deaths annually. An increasing NHL incidence at a rate of 3-4% per year was observed for the 1970s and 1980s. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Hodgkin Lymphoma
- What is being tested?
- Lenalidomide/Rituximab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteFrance
- Study dates
- Sep 2013to Jan 2020
- Phase
- Phase 2
- 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
- Age ≥ 18 years.
- Diagnosis of relapsed or refractory to previous therapy biopsy-proven Diffuse Large B cell non-Hodgkin's Lymphoma (there is no limit on the number of prior therapies. Subjects who have relapsed following an autologous stem cell transplant are eligible.)
- Measurable disease on cross sectional imaging that is at least 2 cm in the longest diameter.
- ECOG (Eastern Cooperative Oncology Group) performance status score of 0, 1, or 2.
- Life expectancy of >= 90 days (3 months).
- Must be able to adhere to the study visit schedule and other protocol requirements.
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- Signed informed consent
- Social security program affiliation
- Females of childbearing potential (FCBP*) must have negative pregnancy test (sensitivity of at least 25 mIU/mL) prior to starting study drug in accordance with the Global Pregnancy Prevention Plan (PPP, annex 6)
- Females of childbearing potential (FCBP) must agree to use two reliable forms of contraception simultaneously** or to practice complete abstinence from heterosexual intercourse during the following time periods related to this study: 1) for at least 28 days before starting study drug; 2) while participating in the study drug; and 3) for at least 12 months after discontinuation from the study drug.
- Male Subjects must agree to use a latex condom during sexual contact with females of childbearing potential while participating in the study and for at least 28 days following discontinuation from the study even if he has undergone a successful vasectomy.
- Agree not to donate blood, semen or sperm while taking study drug and for 28 days after stopping study drug. Do not share drug with other person. Do not break, chew, or open study drug capsules. Return unused study drug capsules to the study doctor.
Who cannot join
- Any of the following laboratory abnormalities:
- Absolute neutrophil count (ANC) < 1.5 x 109/L.
- Platelet count < 60 x 109/L.
- Calculated creatinine clearance (Cockcroft-Gault formula) of < 50mL/min.
- Serum SGOT/AST or SGPT/ALT 5.0 x upper limit of normal (ULN).
- Serum total bilirubin > 2.0 mg/dL (34 μmol/L)/conjugated bilirubin >0.8mg/dL, except in case of hemolytic anemia.
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- Subjects who are candidates for and willing to undergo an autologous stem cell transplant.
- Subjects who are post allogenic stem cell transplant.
- All subjects with active central nervous system (CNS) lymphoma. Subjects with previous CNS lymphoma that have been treated with chemotherapy, radiotherapy or surgery who have remained asymptomatic for 90 days (3 months) and demonstrate, no CNS lymphoma, as shown by lumbar puncture, CT scan or MRI, are eligible. (If required, lumbar puncture, CT or MRI should be performed during screening process.) Subjects should not be receiving corticosteroids.
- Prior history of malignancies other than NHL (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless the subject has been free of the disease for 5 years
- Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
- Pregnant or lactating females.
- Uncontrolled intercurrent illness including, but not limited to:
- Ongoing, severe or active infection requiring antibiotics.
- Uncontrolled diabetes mellitus as defined by the investigator.
- Chronic symptomatic congestive heart failure (Class III or IV of the New York Heart Association Classification for Heart Disease).
- Unstable angina pectoris, angioplasty, stenting, or myocardial infarctions within 168 days (6 months).
- Clinically significant cardiac arrhythmia that is symptomatic or requires treatment, or asymptomatic sustained ventricular tachycardia.
- Prior ≥ Grade 3 allergic reaction/hypersensitivity to thalidomide.
- Prior ≥ Grade 3 rash or any desquamating (blistering) rash while taking thalidomide.
- Subjects with ≥ Grade 2 neuropathy.
- Prior use of lenalidomide.
- Use of any standard or experimental anti-cancer drug therapy within 28 days of the initiation (Day 1) of study drug therapy.
- Known active Hepatitis B or C.
- Known positive for HIV.
- Known hypersensibility to Rituximab or excipients, or to murine proteins,
- Patients with severe immune deficit
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase II Single-arm, Open-label Study to Evaluate the Safety and Efficacy of Combination Lenalidomide (Revlimid®) With Rituximab in Subjets With Relapsed or Refractory Diffuse Large b Cell Non-Hodgkin's Lymphoma.
The incidence of non-Hodgkin's lymphoma (NHL) is steadily increasing worldwide. At present, it is the sixth most commonly diagnosed cancer in France, with 10 000 estimated new cases and 5200 deaths annually. An increasing NHL incidence at a rate of 3-4% per year was observed for the 1970s and 1980s. This stabilized in the 1990s, nevertheless still with an annual rise of 1-2%, resulting in almost a doubling of the NHL incidence during last 40 years. This rise has been noted worldwide, particularly in elderly persons >55 years. Increases in high-grade NHL and extranodal disease are predominant. There is about 80% of B-cell histology, approximately 90% of follicular lymphomas and about 70% of aggressive lymphoma patients present with disseminated disease at diagnosis. The prognosis of NHL depends on the histological type, stage and treatment. Indolent lymphomas have a relatively good prognosis with survival time as long as 10 years, but they are usually incurable in advanced stages. Aggressive NHL constitutes about 50% of all cases of NHL in Western Europe. Approximately 50 - 60% of these patients can be cured with immuno-chemotherapy regiments. Subsequently, almost 50% of patients will eventually relapse or become refractory to treatment. The prognosis for patients with refractory or relapsed aggressive NHL is generally poor. The response rates to salvage therapy regimens range from 20 to 40%. Patients who present with refractory disease have the worst prognosis, with a median survival of less than six months. Only a minority of patients can be given high dose chemotherapy, the majority being ineligible due to disease progression.
By modulating the immune system through dendritic cells and NK cells, by changing the cytokine milieu, and by their anti-angiogenic effects, IMiDs in combination with mabthera (rituximab) resulted in augmented in vitro and vivo antitumor effects against B-cell lymphoma.
Read more
As concerns the timing of administration and doses of medications, phase I/II studies are ongoing with R-CHOP in combination with Revlimid (Lenalidomide) in DLBCL. The latest presentation is by Nowakowski et al. at ASCO meeting in June 2010. This study determined the maximum tolerated dose of Revlimid(Lenalidomide)administered on days 1-10 with standard R-CHOP (R2-CHOP). NO DLT was found and 25 mg of Revlimid(Lenalidomide)was the recommended dose for phase II with enrollment of 32 patients. These encouraging results permit to introduce in our much less toxic protocol 25 mg of Revlimid(Lenalidomide)as initial dose, with progressive reduction in case of toxicity.
As regards the dose and timing of Mabthera(Rituximab), in DLBCL it was traditionally used as a single 375 mg/m2 injection/cycle. Pre-clinical data suggests that for the optimal NK enhancement Revlimid(Lenalidomide)must be administrated several days (approx. 7 days) before Mabthera(Rituximab)injection. So, our protocol provides Mabthera(Rituximab)IV administration at day 7 of Revlimid(Lenalidomide).
Performed parallel biological investigation of NK status will permit to confirm this hypothesis with possible correction of timing and number of administrations of Mabthera(Rituximab)par cycle.
- Conditions
- Non-Hodgkin Lymphoma
- Being tested
- Lenalidomide/Rituximab
- Keywords
- diffuse large B cell, non-Hodgkin lymphoma
- Medical subject headings
- Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lenalidomide/RituximabDrug
| Study group | Role | What they receive |
|---|---|---|
| Lenalidomide/Rituximab | Experimental | Association of Lenalidomide and Rituximab Receives: Drug: Lenalidomide/Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response Rate
The efficacy is evaluated by the response rate defined as complete and partial response or stable disease.according to Cheson 2007 criteria and by PET-SCAN
Measured: at 6 months
Secondary outcomes (2)
Progression
- Duration of response defined from the time when criteria for response (CR or PR) are met to the first documentation of relapse or progression.
- Time to Progression defined as the time from randomisation to first documentation of objective tumour progression (date of tumour assessment documenting progressive disease) or to death due to lymphoma whichever comes first. Progression is assessed by CT scan and/or bone marrow biopsy according to Cheson criteria modified in 2007.
- Progression free survival defined as the time from inclusion to progression
- Tumor control rate : complete response, complete response unconfirmed, partial response, and stable disease
Measured: at 6 months
safety
The safety of the study treatment will be assessed on occurrence of Adverse Events (AEs), graded based on NCI CTCAE v4.0 classification.
Measured: up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2013 (estimated)
- Study startSep 2013
- Primary completionOct 2017
- Study completionJan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Hodgkin LymphomaStudies of the same condition, open and under way.
- More trials run by Institut Paoli-CalmettesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institut Paoli-Calmettes
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Vadim IVANOV, MD, Principal investigator, Institut Paoli-Calmettes
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01939327
- Sponsor's protocol ID
- R2/IPC-2012-004
- Acronym
- R2
- Status last verified
- May 2020
- First submitted
- 29 Aug 2013
- Last updated
- 11 May 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Single-arm, Open-label Study to Evaluate the Safety and Efficacy of Combination Lenalidomide (Revlimid®) With Rituximab in Subjets With Relapsed or Refractory Diffuse Large b Cell Non-Hodgkin's Lymphoma.
- ClinicalTrials.gov ID
- NCT01939327
- Acronym / sponsor ID
- R2 / R2/IPC-2012-004
- Conditions
- Non-Hodgkin Lymphoma
- Keywords
- diffuse large B cell, non-Hodgkin lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Institut Paoli-CalmettesUniversity, hospital or other
- Study start
- Sep 2013 (actual)
- Primary completion
- Oct 2017 (actual)
- Study completion
- Jan 2020 (actual)
- First posted
- 11 Sep 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The incidence of non-Hodgkin's lymphoma (NHL) is steadily increasing worldwide. At present, it is the sixth most commonly diagnosed cancer in France, with 10 000 estimated new cases and 5200 deaths annually. An increasing NHL incidence at a rate of 3-4% per year was observed for the 1970s and 1980s. This stabilized in the 1990s, nevertheless still with an annual rise of 1-2%, resulting in almost a doubling of the NHL incidence during last 40 years. This rise has been noted worldwide, particularly in elderly persons >55 years. Increases in high-grade NHL and extranodal disease are predominant. There is about 80% of B-cell histology, approximately 90% of follicular lymphomas and about 70% of aggressive lymphoma patients present with disseminated disease at diagnosis. The prognosis of NHL depends on the histological type, stage and treatment. Indolent lymphomas have a relatively good prognosis with survival time as long as 10 years, but they are usually incurable in advanced stages. Aggressive NHL constitutes about 50% of all cases of NHL in Western Europe. Approximately 50 - 60% of these patients can be cured with immuno-chemotherapy regiments. Subsequently, almost 50% of patients will eventually relapse or become refractory to treatment. The prognosis for patients with refractory or relapsed aggressive NHL is generally poor. The response rates to salvage therapy regimens range from 20 to 40%. Patients who present with refractory disease have the worst prognosis, with a median survival of less than six months. Only a minority of patients can be given high dose chemotherapy, the majority being ineligible due to disease progression.
By modulating the immune system through dendritic cells and NK cells, by changing the cytokine milieu, and by their anti-angiogenic effects, IMiDs in combination with mabthera (rituximab) resulted in augmented in vitro and vivo antitumor effects against B-cell lymphoma.
As concerns the timing of administration and doses of medications, phase I/II studies are ongoing with R-CHOP in combination with Revlimid (Lenalidomide) in DLBCL. The latest presentation is by Nowakowski et al. at ASCO meeting in June 2010. This study determined the maximum tolerated dose of Revlimid(Lenalidomide)administered on days 1-10 with standard R-CHOP (R2-CHOP). NO DLT was found and 25 mg of Revlimid(Lenalidomide)was the recommended dose for phase II with enrollment of 32 patients. These encouraging results permit to introduce in our much less toxic protocol 25 mg of Revlimid(Lenalidomide)as initial dose, with progressive reduction in case of toxicity.
As regards the dose and timing of Mabthera(Rituximab), in DLBCL it was traditionally used as a single 375 mg/m2 injection/cycle. Pre-clinical data suggests that for the optimal NK enhancement Revlimid(Lenalidomide)must be administrated several days (approx. 7 days) before Mabthera(Rituximab)injection. So, our protocol provides Mabthera(Rituximab)IV administration at day 7 of Revlimid(Lenalidomide).
Performed parallel biological investigation of NK status will permit to confirm this hypothesis with possible correction of timing and number of administrations of Mabthera(Rituximab)par cycle.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lenalidomide/Rituximab | Experimental | Drug: Lenalidomide/RituximabAssociation of Lenalidomide and Rituximab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Age ≥ 18 years.
- Diagnosis of relapsed or refractory to previous therapy biopsy-proven Diffuse Large B cell non-Hodgkin's Lymphoma (there is no limit on the number of prior therapies. Subjects who have relapsed following an autologous stem cell transplant are eligible.)
- Measurable disease on cross sectional imaging that is at least 2 cm in the longest diameter.
- ECOG (Eastern Cooperative Oncology Group) performance status score of 0, 1, or 2.
- Life expectancy of >= 90 days (3 months).
Key exclusion criteria (27 listed)
- Any of the following laboratory abnormalities:
- Subjects who are candidates for and willing to undergo an autologous stem cell transplant.
- Subjects who are post allogenic stem cell transplant.
- All subjects with active central nervous system (CNS) lymphoma. Subjects with previous CNS lymphoma that have been treated with chemotherapy, radiotherapy or surgery who have remained asymptomatic for 90 days (3 months) and demonstrate, no CNS lymphoma, as shown by lumbar puncture, CT scan or MRI, are eligible. (If required, lumbar puncture, CT or MRI should be performed during screening process.) Subjects should not be receiving corticosteroids.
- Prior history of malignancies other than NHL (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless the subject has been free of the disease for 5 years
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lenalidomide/Rituximab | Drug | Lenalidomide/Rituximab |
Primary outcome
Response Rate
Time frame: at 6 months
The efficacy is evaluated by the response rate defined as complete and partial response or stable disease.according to Cheson 2007 criteria and by PET-SCAN
2 secondary outcomes
Progression
Time frame: at 6 months
safety
Time frame: up to 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2020.
- official web site of the sponsorLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vadim IVANOV, MD principal investigator
Institut Paoli-Calmettes
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lenalidomide/Rituximab in people with Non-Hodgkin Lymphoma, run by Institut Paoli-Calmettes at 1 site 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 12 inclusion and 27 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 11 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Response Rate (time frame: at 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 May 2020.