Novel Combination Therapy in the Treatment of Relapsed and Refractory Aggressive B-Cell Lymphoma

NCT02436707 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: LY17
• Study Type: interventional
• Target: 129
• Locations: 1 country
• Sites: 11

Brief Summary

The purpose of this study is to find out what effects new combinations of treatment will have this disease. New promising treatment strategies will be added to this study as they are available to be compared against the standard treatment.

Conditions

Lymphoma

Outcome Measures

Primary Outcomes (1)

• Measure overall response rate

  To determine the overall response rate (complete and partial response) to novel combination therapy in patients with relapsed and refractory aggressive B cell lymphoma

  2 years

Secondary Outcomes (5)

• Number and severity of adverse events

  2 years

• Transplantation rate

  2 years

• Stem cell collection rate

  2 years

• Event free Survival Rate

  2 years

• Overall Survival

  2 years

Study Arms (4)

R-GDP

ACTIVE COMPARATOR

Rituximab - 375 mg/m2 IV, 1.5 - 6 hours D1 (prior to cisplatin); Gemcitabine - 1000 mg/m2, IV 30 min D1, D8; Dexamethasone - 40 mg daily PO D1 - D4; Cisplatin - 75 mg/m2 IV, 1 hour D1;

Drug: Rituximab; Drug: Gemcitabine; Drug: Dexamethasone; Drug: Cisplatin

Ibrutinib plus R-GDP (ACCRUAL COMPLETE)

EXPERIMENTAL

Ibrutinib 560 mg PO -- D1 - D21 Rituximab 375 mg/m2 IV 1.5 - 6 hours D1 (prior to cisplatin) Gemcitabine 1000 mg/m2 IV 30 min D1, D8 Dexamethasone 40 mg daily PO -- D1 - D4 Cisplatin 75 mg/m2 IV 1 hour D1

Drug: Ibrutinib; Drug: Rituximab; Drug: Gemcitabine; Drug: Dexamethasone; Drug: Cisplatin

R-DICEP (ACCRUAL COMPLETE)

EXPERIMENTAL

Rituximab 375 mg/m2 IV 1.5-6hrs Day 1 and Day 5 prior to Cisplatin Mesna 1.75 g/m2 IV 24 hour Cycle 1, Day 2, Day 3 and Day 4 Cyclophosphamide, 1.75 g/m2 IV 2 hours, Day 2, Day 3 and Day 4 Etoposide 350 mg/m2 IV 2 hours, Day 2, Day 3 and Day 4 Cisplatin 35 mg/m2 IV, 2 hours, Day 2, Day 3 and Day 4 G-CSF 300 mcg (\<60kg); 480 mcg (60-90kg); 600 mcg (\>90kg); SC, Daily, starting Day 15 until apheresis completed.

Drug: Rituximab; Drug: Cisplatin; Drug: Mesna; Drug: Cyclophosphamide; Drug: Etoposide; Drug: G-CSF

Selinexor + R-GDP

EXPERIMENTAL

Selinexor - 40mg PO, D1, D3, D8 Rituximab - 375 mg/m2 IV, 1.5 - 6 hours D1 (prior to cisplatin); Gemcitabine - 1000 mg/m2, IV 30 min D1, D8; Dexamethasone - 40 mg daily PO D1 - D4; Cisplatin - 75 mg/m2 IV, 1 hour D1;

Drug: Rituximab; Drug: Gemcitabine; Drug: Dexamethasone; Drug: Cisplatin; Drug: Selinexor

Interventions

Ibrutinib DRUG

Ibrutinib plus R-GDP (ACCRUAL COMPLETE)

Rituximab DRUG

Ibrutinib plus R-GDP (ACCRUAL COMPLETE); R-DICEP (ACCRUAL COMPLETE); R-GDP; Selinexor + R-GDP

Gemcitabine DRUG

Ibrutinib plus R-GDP (ACCRUAL COMPLETE); R-GDP; Selinexor + R-GDP

Cisplatin DRUG

Ibrutinib plus R-GDP (ACCRUAL COMPLETE); R-DICEP (ACCRUAL COMPLETE); R-GDP; Selinexor + R-GDP

Dexamethasone DRUG

Ibrutinib plus R-GDP (ACCRUAL COMPLETE); R-GDP; Selinexor + R-GDP

Mesna DRUG

R-DICEP (ACCRUAL COMPLETE)

Cyclophosphamide DRUG

R-DICEP (ACCRUAL COMPLETE)

Etoposide DRUG

R-DICEP (ACCRUAL COMPLETE)

G-CSF DRUG

R-DICEP (ACCRUAL COMPLETE)

Selinexor DRUG

Selinexor + R-GDP

Eligibility Criteria

• Age: 16 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologic diagnosis for one of the following histologies according to the World Health Organization: documented at initial diagnosis or at relapse:
• Diffuse large cell lymphoma, B-cell (includes primary mediastinal B-cell lymphoma, T-cell rich B-cell lymphoma);
• Previous indolent lymphoma (follicular lymphoma, marginal zone lymphoma, including extranodal MALT lymphoma, lymphoplasmacytoid lymphoma) with transformation to diffuse large B-cell lymphoma at most recent relapse (biopsy proof of transformation is mandatory);
• Unclassifiable B-cell lymphoma with indeterminate features between diffuse large B-cell lymphoma and Burkitt lymphoma.
• Biopsy proof of disease at initial diagnosis is mandatory. A repeat biopsy in primary refractory disease is preferred but not mandatory to confirm progressive disease. A biopsy at relapse is preferred but not mandatory. Participating centres must designate a local reference expert pathologist who will confirm the diagnosis for the patients enrolled at that centre.
• Patients must be CD20+ in order to be eligible for the study.
• Clinically and/or radiologically measurable disease (one site bidimensionally measurable). Measurements/ evaluations must be done within 28 days prior to randomization.
• Prior FDG-PET scan, if done at baseline, must be positive (known FDG-avid lymphoma)
• Patients with de novo aggressive B-cell lymphoma must have relapsed or progressed, or have refractory disease, after 1 prior line of therapy (R-CHOP chemotherapy or equivalent). Patients with histological transformation from low grade lymphoma may have had up to 3 prior treatment regimens. Patients with transformed low grade lymphoma treated with a non-anthracycline regimen may be enrolled at investigator discretion.
• Patient age is ≥16 years. Patients older than 65 years of age are not recommended for this study.
• ECOG performance status of 0, 1 or 2.
• Patient must be considered fit for intensive chemotherapy and ASCT, and an appropriate candidate to receive second-line salvage chemotherapy and ASCT.
• Life expectancy \> 90 days.
• Laboratory Requirements: (must be done within 14 days of randomization)
• Hematology:

You may not qualify if:

• Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer and superficial bladder cancer, curatively treated in-situ cancer of the cervix or breast, or localized excised prostate cancer, other solid tumours curatively treated with no evidence of disease for ≥ 3 years.
• Active and uncontrolled central nervous system involvement, meningeal or parenchymal. Patients with CNS disease at initial presentation and who are in a CNS CR at the time of relapse are eligible. MRI scanning and / or lumbar puncture should be performed if there is clinical suspicion of active CNS disease.
• Major surgery performed within 10 days of randomization.
• Known history of human immunodeficiency virus (HIV), active Hepatitis C Virus infection, active Hepatitis B Virus infection or any uncontrolled active systemic infection requiring intravenous (IV) antibiotics. Patients with Hepatitis B serology suggestive of infection are eligible if they are HBV DNA negative and concurrently treated with anti-viral therapy. Patients with a past history of hepatitis C who have eradicated the virus are eligible.
• Patients who have been vaccinated with live, attenuated vaccines within 4 weeks of randomization.
• Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification.
• Any serious active disease or co-morbid medical condition, including psychiatric illness, judged by the local investigator to preclude safe administration of the planned protocol treatment or required follow-up.
• Any other serious intercurrent illness, life threatening condition, organ system dysfunction, or medical condition judged by the local investigator to compromise the subject's safety, interfere with the absorption or metabolism of selinexor tablets, or preclude safe administration of the planned protocol treatment or required follow-up, including (for example):
• active, uncontrolled bacterial, fungal, or viral infection;
• clinically significant cardiac dysfunction or cardiovascular disease.
• Pregnant or lactating females, or women of childbearing potential not willing to use an adequate method of birth control for the duration of the study.
• Patients are not eligible if they have a known hypersensitivity to the study drugs or their components.

Sponsors & Collaborators

• Canadian Cancer Trials Group: lead
• Janssen, LP: collaborator
• Roche Pharma AG: collaborator
• Karyopharm Therapeutics Inc: collaborator

Study Sites (11)

Arthur J.E. Child Comprehensive Cancer Centre

Calgary, Alberta, T2N 5G2, Canada

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

BCCA - Vancouver

Vancouver, British Columbia, V5Z 4E6, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

QEII Health Sciences Centre

Halifax, Nova Scotia, B3H 1V7, Canada

Location

Kingston Health Sciences Centre

Kingston, Ontario, K7L 2V7, Canada

Location

Ottawa Hospital Research Institute

Ottawa, Ontario, K1H 8L6, Canada

Location

University Health Network

Toronto, Ontario, M5G 2M9, Canada

Location

CHUM-Centre Hospitalier de l'Universite de Montreal

Montreal, Quebec, H2X 3E4, Canada

Location

CHU de Quebec-Hopital l'Enfant-Jesus (HEJ)

Québec, Quebec, G1J 1Z4, Canada

Location

Allan Blair Cancer Centre

Regina, Saskatchewan, S4T 7T1, Canada

Location

Related Publications (1)

• Stewart DA, Kuruvilla J, Lee D, Dudebout JJ, Chua N, Larouche JF, Baetz T, Shafey M, Abdel-Samad N, Robinson S, Fleury I, Fraser G, Skrabek P, Kukreti V, Kelly J, Hay AE, Shepherd LE, Chen BE, Crump M. Canadian cancer trials group LY.17: A randomized phase II study evaluating novel salvage therapy pre-autologous stem cell transplant in relapsed/refractory diffuse large B-cell lymphoma-outcome of rituximab-dose-intensive cyclophosphamide, etoposide, cisplatin (R-DICEP) versus R-GDP. Br J Haematol. 2024 Sep;205(3):881-890. doi: 10.1111/bjh.19555. Epub 2024 May 27.

  PMID: 38802107 RESULT

MeSH Terms

Conditions

Lymphoma

Interventions

ibrutinib; Rituximab; Gemcitabine; Dexamethasone; Cisplatin; Mesna; Cyclophosphamide; Etoposide; Granulocyte Colony-Stimulating Factor; selinexor

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Glucosides; Glycosides; Carbohydrates; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors

Study Officials

• Michael Crump

  Univ. Health Network-OCI/Princess Margaret Hospital, Toronto ON Canada

  STUDY CHAIR

• John Kuruvilla

  Univ. Health Network-Princess Margaret Hospital, Toronto ON Canada

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: May 4, 2015
• First Posted: May 7, 2015
• Study Start: October 27, 2015
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 20, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (11)