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LymphomaPhase 2NCT02436707

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

A Phase 2 study testing Ibrutinib, Rituximab and Gemcitabine in people with Lymphoma, run by Canadian Cancer Trials Group at 11 sites in Canada.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 16 to 65 years
Conditions the study is for
Lymphoma
What is being tested?
Ibrutinib, Rituximab and Gemcitabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
129 participants
Where
11 sitesCanada
Study dates
27 Oct 2015to 31 Dec 2026
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 16 to 65 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.
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  • 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:
  • Granulocytes (AGC) ≥ 1.0 x 10^9/L (independent of growth factor support)
  • Platelets ≥ 100 x 10^9/L (50 x 10^9/L if bone marrow involvement by lymphoma, independent of transfusion support)
  • Biochemistry:
  • AST and ALT ≤ 3x ULN (if both are done, both must be <3x UNL)
  • Serum total bilirubin ≤ 1.5x ULN (≤ 5x ULN if Gilberts Disease)
  • Serum Creatinine ≤ 1.5x ULN (or estimated GFR of ≥ 40 mL/min/1.73m2 using Cockcroft Gault formula).
  • Women must be post-menopausal, surgically sterile or use reliable forms of contraception while on study. Women of child bearing potential and men who are sexually active must be practicing a highly effective method of birth control during and after the study consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials. Men must agree to not donate sperm during and after the study. These restrictions apply for 12 months (1 year) after the last dose of study drug.
  • Women of childbearing potential must have a pregnancy test taken (either by serum beta-human chorionic gonadotropin [B-hCG]) or urine) and proven negative within 14 days prior to randomization. Women who are pregnant or breastfeeding are ineligible for this study.
  • Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate.
  • Patients must be accessible for treatment and follow up. Patients randomized on this trial must be treated and followed at the participating centre. This implies there must be reasonable geographical limits (for example: 1 ½ hour's driving distance) placed on patients being considered for this trial. Investigators must assure themselves the patients randomized on this trial will be available for complete documentation of the treatment, response assessment, adverse events, and follow-up.
  • In accordance with CCTG policy, protocol treatment is to begin within 5 working days of patient randomization.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

Canada11 sites

  • Arthur J.E. Child Comprehensive Cancer Centre

    Calgary, Alberta, T2N 5G2

  • Cross Cancer Institute

    Edmonton, Alberta, T6G 1Z2

  • QEII Health Sciences Centre

    Halifax, Nova Scotia, B3H 1V7

  • Kingston Health Sciences Centre

    Kingston, Ontario, K7L 2V7

  • CHUM-Centre Hospitalier de l'Universite de Montreal

    Montreal, Quebec, H2X 3E4

  • Ottawa Hospital Research Institute

    Ottawa, Ontario, K1H 8L6

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

    Québec, Quebec, G1J 1Z4

  • Allan Blair Cancer Centre

    Regina, Saskatchewan, S4T 7T1

  • University Health Network

    Toronto, Ontario, M5G 2M9

  • BCCA - Vancouver

    Vancouver, British Columbia, V5Z 4E6

  • CancerCare Manitoba

    Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

About this study

Official title: A Multi-Stage Randomized Phase II Study of Novel Combination Therapy in the Treatment of Relapsed and Refractory Aggressive B-Cell Lymphoma

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.

Read the detailed description

This research is being done to try to find new combinations of treatment that may be better for treating patients with this disease. It is not clear however if these treatments can offer better results than standard treatment.

The study uses a "pick the winner" design to facilitate efficient screening of novel combination treatment regimens and select those meeting pre-specified criteria for testing in the phase III setting. All novel treatment options will be compared against the standard treatment for this disease: rituximab plus gemcitabine, dexemthasone, and cisplatin (R-GDP).

Conditions
Lymphoma
Medical subject headings
Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02436707
Study groupRoleWhat they receive
R-GDPActive comparatorRituximab - 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;
Receives: Drug: Rituximab; Drug: Gemcitabine; Drug: Dexamethasone; Drug: Cisplatin
Ibrutinib plus R-GDP (ACCRUAL COMPLETE)ExperimentalIbrutinib 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
Receives: Drug: Ibrutinib; Drug: Rituximab; Drug: Gemcitabine; Drug: Dexamethasone; Drug: Cisplatin
R-DICEP (ACCRUAL COMPLETE)ExperimentalRituximab 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.
Receives: Drug: Rituximab; Drug: Cisplatin; Drug: Mesna; Drug: Cyclophosphamide; Drug: Etoposide; Drug: G-CSF
Selinexor + R-GDPExperimentalSelinexor - 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;
Receives: Drug: Rituximab; Drug: Gemcitabine; Drug: Dexamethasone; Drug: Cisplatin; Drug: Selinexor

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 2 years

Secondary outcomes (5)

  1. Number and severity of adverse events

    To evaluate the tolerability and toxicity of novel combinations. Adverse events will be monitored on an ongoing basis by the central office and their frequencies reported annually at investigators' meetings. Safety and tolerability will be reviewed in the first six patients assigned to ibrutinib plus R-GDP as part of a safety run-in. Ibrutinib dose will be reduced for subjects subsequently enrolled if necessary

    Measured: 2 years

  2. Transplantation rate

    A non-inferiority analysis of transplantation rate will be conducted with 10% non-inferiority margin. The one-sided 80% asymptotic confidence limit of the difference in transplantation rate will be calculated between treatment and control arms.

    Measured: 2 years

  3. Stem cell collection rate

    Stem cell collection rate defined as collection of ≥ 2 x 106 CD34+ cells/kg.

    Measured: 2 years

  4. Event free Survival Rate

    • Event free survival (EFS) at one year defined as time from study entry to any treatment failure including disease progression, or discontinuation of treatment for any reason

    Measured: 2 years

  5. Overall Survival

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 May 2015 (estimated)
  2. Study start27 Oct 2015
  3. Primary completion31 Dec 2026 (estimated)
  4. Study completion31 Dec 2026 (estimated)

Resources

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
129 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02436707
Sponsor's protocol ID
LY17
Status last verified
Apr 2026
First submitted
4 May 2015
Last updated
17 Sep 2026
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • 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.

    PubMed 38802107

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ibrutinib, Rituximab and Gemcitabine in people with Lymphoma, run by Canadian Cancer Trials Group at 11 sites in Canada.

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 26 inclusion and 12 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: under way, not looking for participants, as of the sponsor's last update on 17 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in Canada. 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?

This study is still under way. Results are not available in the source record yet.

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?

Measure overall response rate (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02436707, which also lists 1 linked publication.

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 17 Sep 2026.

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