Diffuse Large B-Cell LymphomaPhase 2LEGENDNCT02060656
Phase II Study Comparing LR-GEM to R-GEM-P in Second-line Treatment of Diffuse Large B-cell Lymphoma (LEGEND)
A Phase 2 study testing Gemcitabine, Methylprednisolone and Rituximab in people with Diffuse Large B-Cell Lymphoma, run by Royal Marsden NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
This is a randomised, phase II open-labelled two-arm study comparing R-GEM-P and LR-GEM in second-line treatment of Diffuse Large B-cell lymphoma. Eligible patients will be randomised 1:1 between R-GEM-P and LR-GEM. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diffuse Large B-Cell Lymphoma
- What is being tested?
- Gemcitabine, Methylprednisolone and Rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 92 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Sep 2013to Aug 2023
- 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
- Histologically proven CD20+ Diffuse Large B-Cell Lymphoma
- Availability of a tumour block containing adequate histological material for central pathology review, establishment of morphological and ontogenic subtype.
- Surgically acquired tissue samples are preferred but if core biopsy is the only suitable means by which to acquire a tissue sample then it is suggested than at least 2 cores are taken so that one can be embedded and sent for central review and one retained locally.
- Relapsed after or refractory to one prior line of chemotherapy for DLBCL containing both rituximab and an anthracycline. Relapsed is defined as investigator assessed progression after first line treatment. Refractory is defined as patients who progressed during or who did not achieve complete remission with first line treatment (which should include radiotherapy if the patient had localised refractory disease)
- Eligible for combination chemotherapy regimen.
- Patient is 18 years of age on the day of signing informed consent.
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- ECOG performance status 0, 1 or 2.
- Baseline PET or CT scans must demonstrate FDG avid disease compatible with CT defined anatomical tumour sites.
- Adequate bone marrow function: absolute neutrophil count (ANC) 1.0x109/l, white blood cell count 3x109/l, platelets 100x109/l, haemoglobin (Hb) 9g/dl (can be post-transfusion), unless deemed disease related
- Adequate renal function: calculated creatinine clearance 40ml/minute.
- Adequate liver function: serum bilirubin 1.5x ULN, ALT/AST 2.5x ULN, ALP 3x ULN (in the absence of liver metastases). If liver metastases are present, ALT, AST or ALP 5x ULN are permitted. Isolated hyperbilirubinaemia due to Gilbert's disease is acceptable.
- Female patient of childbearing potential (FCBP) must have two negative serum β-hCG pregnancy tests at baseline.
- FCBP agreeable to practice complete and true sexual abstinence or use two forms of contraception from 28 days prior to the period of study treatment and for 12 months after the last dose of study drugs.
- Male patients agreeable to practice complete and true sexual abstinence or use condoms from 28 days prior to the period of study treatment and for 12 months after the last dose of study drugs.
- Recovery from toxicity from previous anti-cancer treatment to grade 1.
Who cannot join
- Documented or symptomatic central nervous system involvement or leptomeningeal disease.
- Any other clinically significant disease or co-morbidity which may adversely affect the safe delivery of treatment within this trial, including active or chronic infection,poorly controlled diabetes mellitus, congestive cardiac failure, cardiac arrhythmia, coronary artery disease, cerebrovascular disease, or severe pulmonary disease.
- Any other malignancies diagnosed or treated within the last 5 years (other than curatively treated basal cell or squamous cell carcinoma of the skin and/or in situ carcinoma of the cervix or breast).
- Received drug treatment for cancer within 21 days of commencing study treatment.
- Received previous lenalidomide
- Evidence of human immunodeficiency virus infection, hepatitis C virus, acute or active hepatitis B infection.
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- Patient is pregnant or breastfeeding, or expecting to conceive or father children within one year of finishing study treatment.
- Hypersensitivity or contraindication to any of the study drugs as stated in the SmPCs for each of the study drugs.
- Prior stem cell or solid organ transplant
- Treatment with an investigational product within 30 days prior to enrollment
- Not able to provide fully informed consent because of intellectual impairment or psychiatric disorder
- Patient unwilling or not able to adhere to the Lenalidomide Pregnancy Prevention Programme.
- Treatment with combined oral contraceptive pill within 30 days prior to enrollment.
- Treatment with hormone replacement therapy within 30 days prior to enrollment
- Treatment with erythropoeitic agents within 30 days prior to enrollment
- Baseline hearing impairment, which in the opinion of the investigator, may significantly worsen with treatment with cisplatin.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Royal Marsden NHS Foundation Trust - London and Surrey
London, SM2 5PT
About this study
Official title: A Randomised Phase II Study Comparing LEnalidomide Plus Rituximab, GEmcitabine and Methylprednisolone (LR-GEM) to Rituximab, Gemcitabine, Methylprednisolone and cisplatiN (R-GEM-P) in Second-line Treatment of Diffuse Large B-cell Lymphoma (DLBCL).
This is a randomised, phase II open-labelled two-arm study comparing R-GEM-P and LR-GEM in second-line treatment of Diffuse Large B-cell lymphoma. Eligible patients will be randomised 1:1 between R-GEM-P and LR-GEM.
Read the detailed description
Objectives:
Primary
To assess the complete response rate to LR-GEM (lenalidomide, rituximab, gemcitabine and methylprednisolone) and R-GEM-P (rituximab, gemcitabine,cisplatin and methylprednisolone) following 3 cycles of induction treatment as secondline therapy for patients with Diffuse Large B-cell Lymphoma.
To investigate in both arms:
- Overall response rate following 3 cycles of induction treatment evaluated by IWG 2007 criteria
- Event-free survival
- Overall survival
- Rate of successful stem cell harvest
- Toxicity
- Subgroup analyses will be performed on the primary endpoint by cell-of-origin immunohistochemical subtype using the Choi method[2] (GCB vs non-GCB), morphological subtype (centroblastic vs immunoblastic vs other), IPI (0-1 vs ³2),and previous response to treatment (£12 vs > 12 months), and eligibility for ASCT at randomisation.
Treatment:
LR-GEM: lenalidomide plus rituximab, gemcitabine and methylprednisolone every 28 days. R-GEM-P: rituximab, gemcitabine, methylprednisolone and cisplatin every 28 days.
Assessment Schedule:
- Patients will be reviewed at baseline and prior to each scheduled dose of treatment for toxicity
- Radiological tumour assessment will be done with contrast-enhanced CT scan after the 1st and 3rd cycles in both arms.
- PET/CT scan will be performed at baseline and upon completion of induction treatment (3-4 weeks after last dose of chemotherapy). If PET/CT scan is performed with a contrast-enhanced CT, then patients do not need a separate CT scan.
- Follow up after completion of induction treatment will be at 3 monthly intervals for the first 12 months in Arm A and at monthly intervals for the first 12 months for patients in Arm B. Thereafter follow up in both Arm A and B will be at 6 monthly intervals for 2 years, then annually up until 5 years in total.
- CT scan at 3 \& 12 months post induction treatment in both arms
- Following disease progression patients will be followed for survival every 3 months until death
- Conditions
- Diffuse Large B-Cell Lymphoma
- Being tested
- Gemcitabine, Methylprednisolone, Rituximab, Cisplatin, Lenalidomide
- Keywords
- Relapsed or refractory Diffuse Large B-Cell Lymphoma after R-CHOP chemotherapy
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GemcitabineDrug
1000mg/m2 IV D1, D8, D15 every 28 days
1000mg/m2 IV or PO D1-5 every 28 days
RituximabDrug
375mg/m2 IV D1, D15 every 28 days
CisplatinDrug
100mg/m2 IV D15 every 28 days
LenalidomideDrug
25mg PO D1-21 every 28 days
| Study group | Role | What they receive |
|---|---|---|
| Control: R-GEM-P | Active comparator | Rituximab,Gemcitabine, Methylprednisolone,Cisplatin. Receives: Drug: Gemcitabine; Drug: Methylprednisolone; Drug: Rituximab; Drug: Cisplatin |
| Experimental: LR-GEM | Experimental | Lenalidomide, Rituximab, Gemcitabine, Methylprednisolone Receives: Drug: Gemcitabine; Drug: Methylprednisolone; Drug: Rituximab; Drug: Lenalidomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete response rate (CRR)
Measured: Approximatley after 12 weeks of randomisation
Secondary outcomes (4)
Overall Response Rate
Measured: Approximately 12 weeks after randamisation
Event-free Survival
Measured: This will be calculated from the date of randomisation until the date of treatment failure up to 104 weeks
Overall Survival
Measured: this will be calculated from the date of randomisation until the date of death, irrespective of its cause.
Rates of successful stem cell harvest
Measured: This will be calculated by the amount of stem cells collected and number of stem cell harvest attempts per patient up to 104 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2014 (estimated)
- Study startSep 2013
- Primary completionFeb 2018
- Study completionAug 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diffuse Large B-Cell LymphomaStudies of the same condition, open and under way.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 92 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Royal Marsden NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Celgene Corporation
- Responsible party
- Sponsor
- Investigators
- David Cunningham, MD FRCP, Principal investigator, Royal Marsden NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02060656
- Sponsor's protocol ID
- RMH CCR: 3862
- Other IDs
- 2012-002620-32
- Acronym
- LEGEND
- Status last verified
- Sep 2019
- First submitted
- 22 Jan 2014
- Last updated
- 19 Sep 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Phase II Study Comparing LEnalidomide Plus Rituximab, GEmcitabine and Methylprednisolone (LR-GEM) to Rituximab, Gemcitabine, Methylprednisolone and cisplatiN (R-GEM-P) in Second-line Treatment of Diffuse Large B-cell Lymphoma (DLBCL).
- ClinicalTrials.gov ID
- NCT02060656
- Acronym / sponsor ID
- LEGEND / RMH CCR: 3862
- Conditions
- Diffuse Large B-Cell Lymphoma
- Keywords
- Relapsed or refractory Diffuse Large B-Cell Lymphoma after R-CHOP chemotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 92 participants (estimated)
- Lead sponsor
- Royal Marsden NHS Foundation TrustUniversity, hospital or other
- Collaborators
- Celgene Corporation
- Study start
- Sep 2013 (actual)
- Primary completion
- Feb 2018 (actual)
- Study completion
- Aug 2023 (estimated)
- First posted
- 12 Feb 2014 (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.
This is a randomised, phase II open-labelled two-arm study comparing R-GEM-P and LR-GEM in second-line treatment of Diffuse Large B-cell lymphoma. Eligible patients will be randomised 1:1 between R-GEM-P and LR-GEM.
Detailed description
Objectives:
Primary
To assess the complete response rate to LR-GEM (lenalidomide, rituximab, gemcitabine and methylprednisolone) and R-GEM-P (rituximab, gemcitabine,cisplatin and methylprednisolone) following 3 cycles of induction treatment as secondline therapy for patients with Diffuse Large B-cell Lymphoma.
To investigate in both arms:
- Overall response rate following 3 cycles of induction treatment evaluated by IWG 2007 criteria
- Event-free survival
- Overall survival
- Rate of successful stem cell harvest
- Toxicity
- Subgroup analyses will be performed on the primary endpoint by cell-of-origin immunohistochemical subtype using the Choi method[2] (GCB vs non-GCB), morphological subtype (centroblastic vs immunoblastic vs other), IPI (0-1 vs ³2),and previous response to treatment (£12 vs > 12 months), and eligibility for ASCT at randomisation.
Treatment:
LR-GEM: lenalidomide plus rituximab, gemcitabine and methylprednisolone every 28 days. R-GEM-P: rituximab, gemcitabine, methylprednisolone and cisplatin every 28 days.
Assessment Schedule:
- Patients will be reviewed at baseline and prior to each scheduled dose of treatment for toxicity
- Radiological tumour assessment will be done with contrast-enhanced CT scan after the 1st and 3rd cycles in both arms.
- PET/CT scan will be performed at baseline and upon completion of induction treatment (3-4 weeks after last dose of chemotherapy). If PET/CT scan is performed with a contrast-enhanced CT, then patients do not need a separate CT scan.
- Follow up after completion of induction treatment will be at 3 monthly intervals for the first 12 months in Arm A and at monthly intervals for the first 12 months for patients in Arm B. Thereafter follow up in both Arm A and B will be at 6 monthly intervals for 2 years, then annually up until 5 years in total.
- CT scan at 3 \& 12 months post induction treatment in both arms
- Following disease progression patients will be followed for survival every 3 months until death
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control: R-GEM-P | Active comparator | Drug: Gemcitabine, Drug: Methylprednisolone, Drug: Rituximab, Drug: CisplatinRituximab,Gemcitabine, Methylprednisolone,Cisplatin. |
| Experimental: LR-GEM | Experimental | Drug: Gemcitabine, Drug: Methylprednisolone, Drug: Rituximab, Drug: LenalidomideLenalidomide, Rituximab, Gemcitabine, Methylprednisolone |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Histologically proven CD20+ Diffuse Large B-Cell Lymphoma
- Availability of a tumour block containing adequate histological material for central pathology review, establishment of morphological and ontogenic subtype.
- Surgically acquired tissue samples are preferred but if core biopsy is the only suitable means by which to acquire a tissue sample then it is suggested than at least 2 cores are taken so that one can be embedded and sent for central review and one retained locally.
- Relapsed after or refractory to one prior line of chemotherapy for DLBCL containing both rituximab and an anthracycline. Relapsed is defined as investigator assessed progression after first line treatment. Refractory is defined as patients who progressed during or who did not achieve complete remission with first line treatment (which should include radiotherapy if the patient had localised refractory disease)
- Eligible for combination chemotherapy regimen.
Key exclusion criteria (16 listed)
- Documented or symptomatic central nervous system involvement or leptomeningeal disease.
- Any other clinically significant disease or co-morbidity which may adversely affect the safe delivery of treatment within this trial, including active or chronic infection,poorly controlled diabetes mellitus, congestive cardiac failure, cardiac arrhythmia, coronary artery disease, cerebrovascular disease, or severe pulmonary disease.
- Any other malignancies diagnosed or treated within the last 5 years (other than curatively treated basal cell or squamous cell carcinoma of the skin and/or in situ carcinoma of the cervix or breast).
- Received drug treatment for cancer within 21 days of commencing study treatment.
- Received previous lenalidomide
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 |
|---|---|---|
| Gemcitabine1000mg/m2 IV D1, D8, D15 every 28 days | Drug | Control: R-GEM-P, Experimental: LR-GEM |
| Methylprednisolone1000mg/m2 IV or PO D1-5 every 28 days | Drug | Control: R-GEM-P, Experimental: LR-GEM |
| Rituximab375mg/m2 IV D1, D15 every 28 days | Drug | Control: R-GEM-P, Experimental: LR-GEM |
| Cisplatin100mg/m2 IV D15 every 28 days | Drug | Control: R-GEM-P |
| Lenalidomide25mg PO D1-21 every 28 days | Drug | Experimental: LR-GEM |
Primary outcome
Complete response rate (CRR)
Time frame: Approximatley after 12 weeks of randomisation
4 secondary outcomes
Overall Response Rate
Time frame: Approximately 12 weeks after randamisation
Event-free Survival
Time frame: This will be calculated from the date of randomisation until the date of treatment failure up to 104 weeks
Overall Survival
Time frame: this will be calculated from the date of randomisation until the date of death, irrespective of its cause.
Rates of successful stem cell harvest
Time frame: This will be calculated by the amount of stem cells collected and number of stem cell harvest attempts per patient up to 104 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2019.
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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.
David Cunningham, MD FRCP principal investigator
Royal Marsden NHS Foundation Trust
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 Gemcitabine, Methylprednisolone and Rituximab in people with Diffuse Large B-Cell Lymphoma, run by Royal Marsden NHS Foundation Trust at 1 site in United Kingdom.
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 16 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: status not confirmed, as of the sponsor's last update on 19 Sep 2019. 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 United Kingdom. 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?
Results are not available in the source record.
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?
Complete response rate (CRR) (time frame: Approximatley after 12 weeks of randomisation). 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 19 Sep 2019; AzTrials last refreshed its copy on 31 Oct 2026.