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Lymphoma, B-CellEarly Phase 1NCT04161248

Phase I Master Protocol of Novel Combination Therapy for Patients With Relapsed or Refractory Aggressive B-Cell Lymphoma

A Early Phase 1 study testing Venetoclax, Rituximab Injection and Rituximab SC in people with Lymphoma, B-Cell, run by Canadian Cancer Trials Group at 4 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 the highest dose of a new drug, in combination with standard drugs, which can be tolerated without causing very severe side effects. The study treatment is new agents in combination with R-GDP or an equivalent regimen. Read more about this study

Who is it for?
Ages 16 to 65 years
Conditions the study is for
Lymphoma, B-Cell
What is being tested?
Venetoclax, Rituximab Injection and Rituximab SC
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
4 sitesCanada
Study dates
2 Sep 2020to 31 Dec 2026
Phase
Early Phase 1
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).
  • Patients with de novo aggressive B-cell lymphoma must have relapsed or progressed, or have biopsy-proven refractory disease, after one prior line of therapy (R-CHOP chemotherapy or equivalent). R-CHOP chemotherapy equivalents include R-CEOP, dose-adjusted EPOCH-R, CODOX-M/IVAC-R, and other combination regimens including a CD20 monoclonal antibody, alkylating agent and anthracycline.
  • 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 must be considered fit for intensive chemotherapy and ASCT, and an appropriate candidate to receive second-line salvage chemotherapy and ASCT. Individuals older than 65 years of age are not recommended for this study.
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  • Clinically and / or radiologically measurable disease (1 site dimensionally measurable). Measurements / evaluations must be done within 28 days prior to enrollment using the RECIL and Lugano criteria.
  • Age ≥ 16 years. (Note that the lower age limit at each centre will be determined by that centre's policy regarding the age at which an individual may sign his or her own consent.)
  • ECOG performance status 0, 1, 2 or 3.
  • Life expectancy of ≥ 90 days (3 months).
  • Laboratory Requirements: (must be done within 14 days of enrollment)
  • Absolute Neutrophil ≥ 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)
  • AST and ALT ≤ 3x ULN
  • Serum total bilirubin≤ 1.5x ULN (≤ 5x ULN if Gilberts Disease)
  • Serum Creatinine ≤ 1.5x ULN (or estimated GFR of ≥ 45 mL/min/1.73 m2 using Cockcroft Gault formula)
  • Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrolment in the trial to document their willingness to participate.
  • Patients must be accessible for treatment and follow up. Patients enrolled on this trial must be treated and followed at the participating centre. This implies there must be reasonable geographical limits (for example: 1 ½ hours driving distance) placed on patients being considered for this trial.
  • In accordance with CCTG policy, protocol treatment is to begin within 5 working days of patient enrollment.
  • Women of childbearing potential who are sexually active must have agreed to use a highly effective contraceptive method during treatment and for 12 months after the end of treatment. Men must not father a baby or donate sperm while taking study treatment, and for 24 months after the last dose.

Who cannot join

  • Patients concurrently receiving any other anti-cancer therapy (cytotoxic, biologic, radiation, or hormonal other than for replacement) except for medications that are prescribed for supportive care but may potentially have an anti-cancer effect.
  • Systemic therapy (cytotoxics, targeted agents and investigational drugs): patients must have recovered from all reversible toxicity related to prior treatment and have adequate washout prior to enrollment with the longest of:
  • Five half-lifes
  • Two weeks
  • Standard cycle length of prior regimen
  • Biologic agents e.g. monoclonal antibodies: not permitted within 28 days prior to enrollment.
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  • Steroids: avoidance of steroids with anti-neoplastic intent in 7 days prior to study drug is preferred. However, if clinically required, it can be administered at investigator discretion (prednisone 40 mg for 4 days maximum, or equivalent) and must be captured on the electronic case report form.
  • Radiation: not permitted within 28 days prior to enrollment.
  • 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.
  • Known history of human immunodeficiency virus (HIV), active Hepatitis C virus infection, active Hepatitis B virus infection or any uncontrolled active systemic infection. 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 history of hepatitis C who have eradicated the virus are eligible.
  • Patients who have been vaccinated with live, attenuated vaccines within 4 weeks of enrollment.
  • Patients with clinically significant pre-existing cardiac conditions, including uncontrolled or symptomatic angina, uncontrolled atrial or ventricular arrhythmias, or symptomatic congestive heart failure.
  • Patients with known left ventricular ejection fraction (LVEF) < 40%.
  • Patients with stroke (including TIA) or acute myocardial infarction within three months prior to enrollment.
  • Patients with acute gastrointestinal bleeding within one month prior to enrollment.
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. However, patients on active anticancer therapy for other advanced or metastatic malignancies are not eligible, as this is a phase I study identifying a RP2D of a single agent and there is the potential for drug-drug interactions. Consult CCTG for patients who are on adjuvant therapies after curative surgery or in instances where it is felt the patient may be eligible (for example, TCC bladder receiving local therapies or CLL not requiring active therapy).
  • 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.
  • Patients with any other clinically significant medical condition which, in the opinion of the treating physician, makes it undesirable for the patient to participate in the study or which could jeopardize compliance with study requirements including, but not limited to: ongoing or active infection, significant uncontrolled hypertension, or severe psychiatric illness/social situations.

Trial locations and contacts

4 sites in 1 country.

Canada4 sites

  • Kingston Health Sciences Centre

    Kingston, Ontario, K7L 2V7

  • The Jewish General Hospital

    Montreal, Quebec, H3T 1E2

  • University Health Network

    Toronto, Ontario, M5G 2M9

  • BCCA - Vancouver

    Vancouver, British Columbia, V5Z 4E6

Other trials in Canada

About this study

Official title: A Phase I Master Protocol of Novel Combination Therapy for Patients With Relapsed or Refractory Aggressive B-Cell Lymphoma

The purpose of this study is to find the highest dose of a new drug, in combination with standard drugs, which can be tolerated without causing very severe side effects. The study treatment is new agents in combination with R-GDP or an equivalent regimen.

Read the detailed description

To find the highest dose of a new drug that can be tolerated without causing severe side effects when receiving R-GDP or an equivalent regimen. This is done by starting at a dose lower than the one that is tolerated in patients when given on its own. Participants are given the new drug together with R-GDP and are watched very closely to see what side effects they have and to make sure the side effects are not severe. If the side effects are not severe, then new participants will be given a higher dose of the new drug. Participants joining the study later on will get higher doses of the new drug than participants who join earlier. This will continue until a dose is found that causes severe but temporary side effects. Doses higher than that will not be given.

Being tested
Venetoclax, Rituximab Injection, Rituximab SC, Gemcitabine, Dexamethasone
Medical subject headings
Lymphoma, B-Cell

What participants receive

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

  • VenetoclaxDrug

    Dose Level -1: Venetoclax 200 mg/day days 4-8 cycle 1, days 1-5 cycle 2 and 3, + R-GDP

    Dose Level 1: Venetoclax 200 mg/day days 4-10 cycle 1, days 1-10 cycle 2 and 3, + R-GDP

    Dose Level 2: Venetoclax 400 mg/day days 4-10 cycle 1, days 1-10 cycle 2 and 3, + R-GDP

    Dose Level 3: Venetoclax 800 mg/day days 4-10 cycle 1, days 1-10 cycle 2 and 3, + R-GDP

  • Rituximab InjectionDrug

    375 mg/m2 - Day 1, cycle 1.

  • Rituximab SCDrug

    1400 mg fixed dose - Day 1, cycle 2 and 3

  • GemcitabineDrug

    1000 mg/m2 - Day 1 to day 8

  • DexamethasoneDrug

    40 mg daily - Day 1 to day 4

  • CisplatinDrug

    75mg/m2 - Day 1

  • GlofitamabDrug

    Cycle 1: Glofitamab 2.5 mg (day 8) and 10 mg (day 15) + R-GDP Cycle 2: Glofitamab 30 mg (day 8) + R-GDP Cycle 3: Glofitamab 30 mg (day 8) + R-GDP

  • TafasitamabDrug

    Cycle 1: Tafasitamab (12 mg/kg IV day -1, 8, 15) Cycles 2 and 3: Tafasitamab (12 mg/kg IV day 1, 8, 15)

Study groups in NCT04161248
Study groupRoleWhat they receive
Venetoclax + R-GDPExperimentalNot described
Receives: Drug: Venetoclax; Drug: Rituximab Injection; Drug: Rituximab SC; Drug: Gemcitabine; Drug: Dexamethasone; Drug: Cisplatin
Glofitamab + R-GDPExperimentalNot described
Receives: Drug: Rituximab Injection; Drug: Rituximab SC; Drug: Gemcitabine; Drug: Dexamethasone; Drug: Cisplatin; Drug: Glofitamab
Tafasitamab + R-GDPExperimentalNot described
Receives: Drug: Tafasitamab

What is being measured

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

  1. Establish maximum tolerated dose of new combination therapy

    Measured: 4 years

  2. Establish recommended Phase II dose of new combination therapy

    Measured: 4 years

Secondary outcomes (7)

  1. Overall response rate using RECIL response criteria

    Measured: 4 years

  2. Overall response rate using the Lugano response criteria

    Measured: 4 years

  3. Severity of adverse events using CTCAE

    Measured: 4 years

  4. Stem cell collection rate

    Measured: 4 years

  5. Transplantation rate

    Measured: 4 years

  6. Event-free survival

    Measured: 4 years

  7. Overall Survival

    Measured: 4 years

Timeline

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

  1. First posted13 Nov 2019
  2. Study start2 Sep 2020
  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
Early Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04161248
Sponsor's protocol ID
LY18
Other IDs
ML40080, A17-190, I-00208-20-06
Status last verified
May 2026
First submitted
8 Nov 2019
Last updated
24 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Assouline S, Prica A, Villa D, Kridel R, Johnson N, Kukreti V, Shamy A, Kaedbey R, Gerrie A, Savage K, Kelly J, Shepherd LE, Hay AE, Scott DW, Crump M, Chen BE, Kuruvilla J. A phase 1 study of R-GDP-venetoclax before autologous transplant in relapsed/refractory large B-cell lymphoma (CCTG LY.18). Blood Neoplasia. 2026 Apr 15;3(3):100233. doi: 10.1016/j.bneo.2026.100233. eCollection 2026 Aug.

    PubMed 42255257

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Venetoclax, Rituximab Injection and Rituximab SC in people with Lymphoma, B-Cell, run by Canadian Cancer Trials Group at 4 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 20 inclusion and 19 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 24 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 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?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

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?

Establish maximum tolerated dose of new combination therapy (time frame: 4 years). The study lists 2 primary outcomes in all. 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 NCT04161248, 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 24 Jun 2026.

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