CCTG LY.18

A phase I master protocol of novel combination therapy for patients with relapsed or refractory lymphoma - The RGDP-Venetoclax substudy

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Population: Hematology - B-cell lymphoma

Line of therapy: Relapsed/Refractory B-cell lymphoma

Intervention: RGDP-Venetoclax

Key Inclusion Criteria

1. 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).

2. Patients w/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).

3. Patients w/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.

4. 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.

5. 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.

6. ECOG performance status 0, 1, 2 or 3.

7. Life expectancy of > 90 days (3 months)

8. Hematology: ANC ≥ 1.0 x 109/L (independent of growth factor support); Platelets ≥ 100 x 109/L (50 x 109/L if bone marrow involvement by lymphoma, independent of transfusion support)

9. Biochemistry: 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/1.73m2 using Cockcroft Gault formula)

   
   

Key Exclusion Criteria

1. 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;

   • 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.

2. Active and uncontrolled central nervous system involvement, meningeal or parenchymal.

3. Known history of human immunodeficiency virus (HIV), active Hepatitis C virus infection, active Hepatitis B virus infection or any uncontrolled active systemic infection.

4. Live, attenuated vaccines within 4 weeks of enrollment.

5. Clinically significant pre-existing cardiac conditions, including uncontrolled or symptomatic angina, uncontrolled atrial or ventricular arrhythmias, or symptomatic congestive heart failure; LVEF < 40%.

6. Stroke (including TIA) or acute myocardial infarction within three months prior to enrollment.

7. Acute gastrointestinal bleeding within one month prior to enrollment

Sponsor: CCTG

CRP Contact:  martha.elbebawy@ladydavis.ca

514-340-8222 ext. 28224

CRP PI: Dr. S. Assouline

Status: Open to accrual