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Phase II Study Comparing LR-GEM to R-GEM-P in Second-line Treatment of Diffuse Large B-cell Lymphoma (LEGEND) (LEGEND)

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ClinicalTrials.gov Identifier: NCT02060656
Recruitment Status : Unknown
Verified February 2014 by Royal Marsden NHS Foundation Trust.
Recruitment status was:  Recruiting
First Posted : February 12, 2014
Last Update Posted : February 12, 2014
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Royal Marsden NHS Foundation Trust

Brief 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.

Condition or disease Intervention/treatment Phase
Diffuse Large B-Cell Lymphoma Drug: Gemcitabine Drug: Methylprednisolone Drug: Rituximab Drug: Cisplatin Drug: Lenalidomide Phase 2

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 92 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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).
Study Start Date : September 2013
Estimated Primary Completion Date : February 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Active Comparator: Control: R-GEM-P
Rituximab,Gemcitabine, Methylprednisolone,Cisplatin.
Drug: Gemcitabine
1000mg/m2 IV D1, D8, D15 every 28 days

Drug: Methylprednisolone
1000mg/m2 IV or PO D1-5 every 28 days

Drug: Rituximab
375mg/m2 IV D1, D15 every 28 days

Drug: Cisplatin
100mg/m2 IV D15 every 28 days

Experimental: Experimental: LR-GEM
Lenalidomide, Rituximab, Gemcitabine, Methylprednisolone
Drug: Gemcitabine
1000mg/m2 IV D1, D8, D15 every 28 days

Drug: Methylprednisolone
1000mg/m2 IV or PO D1-5 every 28 days

Drug: Rituximab
375mg/m2 IV D1, D15 every 28 days

Drug: Lenalidomide
25mg PO D1-21 every 28 days




Primary Outcome Measures :
  1. Complete response rate (CRR) [ Time Frame: Approximatley after 12 weeks of randomisation ]

Secondary Outcome Measures :
  1. Overall Response Rate [ Time Frame: Approximately 12 weeks after randamisation ]
  2. Event-free Survival [ Time Frame: This will be calculated from the date of randomisation until the date of treatment failure up to 104 weeks ]
  3. Overall Survival [ Time Frame: this will be calculated from the date of randomisation until the date of death, irrespective of its cause. ]
  4. 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 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.
  • 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.

Exclusion Criteria:

  • 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.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02060656


Contacts
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Contact: David Cunningham, MD FRCP +44 (0)208 661 3156 david.cunningham@rmh.nhs.uk

Locations
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United Kingdom
Royal Marsden NHS Foundation Trust - London and Surrey Recruiting
London, United Kingdom, SM2 5PT
Contact: Bijal Patel, Msc    +44 (0)208 661 3808    bijal.patel@rmh.nhs.uk   
Principal Investigator: David Cunningham, MD FRCP         
Sponsors and Collaborators
Royal Marsden NHS Foundation Trust
Celgene Corporation
Investigators
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Principal Investigator: David Cunningham, MD FRCP Royal Marsden NHS Foundation Trust

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Responsible Party: Royal Marsden NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT02060656     History of Changes
Other Study ID Numbers: RMH CCR: 3862
2012-002620-32 ( EudraCT Number )
First Posted: February 12, 2014    Key Record Dates
Last Update Posted: February 12, 2014
Last Verified: February 2014

Keywords provided by Royal Marsden NHS Foundation Trust:
Relapsed or refractory Diffuse Large B-Cell Lymphoma after R-CHOP chemotherapy

Additional relevant MeSH terms:
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Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Gemcitabine
Methylprednisolone
Methylprednisolone Acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Cisplatin
Rituximab
Lenalidomide
Prednisolone hemisuccinate
Prednisolone phosphate
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors