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

NCT02060656 | Unknown Phase 2 DMC

• 2 other identifiers: RMH CCR: 38622012-002620-32
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 1

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.

Conditions

Diffuse Large B-Cell Lymphoma

Keywords

Relapsed or refractory Diffuse Large B-Cell Lymphoma after R-CHOP chemotherapy

Outcome Measures

Primary Outcomes (1)

• Complete response rate (CRR)

  Approximatley after 12 weeks of randomisation

Secondary Outcomes (4)

• Overall Response Rate

  Approximately 12 weeks after randamisation

• Event-free Survival

  This will be calculated from the date of randomisation until the date of treatment failure up to 104 weeks

• Overall Survival

  this will be calculated from the date of randomisation until the date of death, irrespective of its cause.

• Rates of successful stem cell harvest

  This will be calculated by the amount of stem cells collected and number of stem cell harvest attempts per patient up to 104 weeks

Study Arms (2)

Control: R-GEM-P

ACTIVE COMPARATOR

Rituximab,Gemcitabine, Methylprednisolone,Cisplatin.

Drug: Gemcitabine; Drug: Methylprednisolone; Drug: Rituximab; Drug: Cisplatin

Experimental: LR-GEM

EXPERIMENTAL

Lenalidomide, Rituximab, Gemcitabine, Methylprednisolone

Drug: Gemcitabine; Drug: Methylprednisolone; Drug: Rituximab; Drug: Lenalidomide

Interventions

Gemcitabine DRUG

1000mg/m2 IV D1, D8, D15 every 28 days

Control: R-GEM-P; Experimental: LR-GEM

Methylprednisolone DRUG

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

Control: R-GEM-P; Experimental: LR-GEM

Rituximab DRUG

375mg/m2 IV D1, D15 every 28 days

Control: R-GEM-P; Experimental: LR-GEM

Cisplatin DRUG

100mg/m2 IV D15 every 28 days

Control: R-GEM-P

Lenalidomide DRUG

25mg PO D1-21 every 28 days

Experimental: LR-GEM

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Royal Marsden NHS Foundation Trust: lead
• Celgene Corporation: collaborator

Study Sites (1)

Royal Marsden NHS Foundation Trust - London and Surrey

London, SM2 5PT, United Kingdom

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Recurrence

Interventions

Gemcitabine; Methylprednisolone; Rituximab; Cisplatin; Lenalidomide

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• David Cunningham, MD FRCP

  Royal Marsden NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2014
• First Posted: February 12, 2014
• Study Start: September 1, 2013
• Primary Completion: February 1, 2018
• Study Completion: August 1, 2023
• Last Updated: September 19, 2019

Record last verified: 2019-09

Locations

GB (1)