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

NCT04161248 | Recruiting Early Phase 1 DMC FDA Drug

• 4 other identifiers: LY18ML40080A17-190I-00208-20-06
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Lymphoma, B-Cell

Outcome Measures

Primary Outcomes (2)

• Establish maximum tolerated dose of new combination therapy

  4 years

• Establish recommended Phase II dose of new combination therapy

  4 years

Secondary Outcomes (7)

• Overall response rate using RECIL response criteria

  4 years

• Overall response rate using the Lugano response criteria

  4 years

• Severity of adverse events using CTCAE

  4 years

• Stem cell collection rate

  4 years

• Transplantation rate

  4 years

Study Arms (3)

Venetoclax + R-GDP

EXPERIMENTAL

Drug: Venetoclax; Drug: Rituximab Injection; Drug: Rituximab SC; Drug: Gemcitabine; Drug: Dexamethasone; Drug: Cisplatin

Glofitamab + R-GDP

EXPERIMENTAL

Drug: Rituximab Injection; Drug: Rituximab SC; Drug: Gemcitabine; Drug: Dexamethasone; Drug: Cisplatin; Drug: Glofitamab

Tafasitamab + R-GDP

EXPERIMENTAL

Drug: Tafasitamab

Interventions

Venetoclax DRUG

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

Venetoclax + R-GDP

Cisplatin DRUG

75mg/m2 - Day 1

Glofitamab + R-GDP; Venetoclax + R-GDP

Rituximab Injection DRUG

375 mg/m2 - Day 1, cycle 1.

Glofitamab + R-GDP; Venetoclax + R-GDP

Rituximab SC DRUG

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

Glofitamab + R-GDP; Venetoclax + R-GDP

Gemcitabine DRUG

1000 mg/m2 - Day 1 to day 8

Glofitamab + R-GDP; Venetoclax + R-GDP

Dexamethasone DRUG

40 mg daily - Day 1 to day 4

Glofitamab + R-GDP; Venetoclax + R-GDP

Glofitamab DRUG

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

Glofitamab + R-GDP

Tafasitamab DRUG

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

Tafasitamab + 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).
• 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.
• 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)

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Canadian Cancer Trials Group: lead
• Roche Pharma AG: collaborator
• AbbVie: collaborator
• Incyte Corporation: collaborator

Study Sites (4)

BCCA - Vancouver

Vancouver, British Columbia, V5Z 4E6, Canada

RECRUITING

Kingston Health Sciences Centre

Kingston, Ontario, K7L 2V7, Canada

RECRUITING

University Health Network

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

The Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

RECRUITING

MeSH Terms

Conditions

Lymphoma, B-Cell

Interventions

venetoclax; Rituximab; Gemcitabine; Dexamethasone; Cisplatin; glofitamab; tafasitamab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; 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

Study Officials

• Sarit Assouline

  The Jewish General Hospital, Montreal QC, Canada

  STUDY CHAIR

• Diego Villa

  BCCA - Vancouver Cancer Centre, BC, Canada

  STUDY CHAIR

• Tara Baetz

  Cancer Centre of Southeastern Ontario at Kingston, ON, Canada

  STUDY CHAIR

Central Study Contacts

Annette Hay

CONTACT

613-533-6430; ahay@ctg.queensu.ca

Lois Shepherd

CONTACT

613-533-6430; lshepherd@ctg.queensu.ca

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2019
• First Posted: November 13, 2019
• Study Start: September 2, 2020
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: February 2, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (4)