A Study of Glofitamab in Combination With Rituximab or Obinutuzumab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP), or Polatuzumab Vedotin Plus Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (CHP) in Participants With Non-Hodgkin Lymphomas or With DLBCL

Part of paid clinical trials in Birmingham, Alabama.

Sponsor
Hoffmann-La Roche
Study ID
NCT03467373
Phase
PHASE1
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Glofitamab — DRUG
    Glofitamab will be administered intravenously (IV) as a step-up dose for Cycle 2 on Days 8 and 15, and as a single dose from Cycle 3 onwards.
  • Obinutuzumab (G) — DRUG
    Obinutuzumab 1000 mg single dose IV infusion on Day 1 of Cycle 1 only
  • Rituximab (R) — DRUG
    Rituximab will be administered as an IV infusion at a dose of 375 mg/m\^2 on Day 1 of each 21-day cycle starting from Cycle 1 to Cycle 6 (Part 1) or from Cycles 1-6 (up to 8) (Part 2: DLBCL R-CHOP).
  • Tocilizumab — DRUG
    Tocilizumab will be administered as an IV infusion as per the methods described in the Summary of Product Characteristics (SmPC) or other similar local prescribing documents. Tocilizumab will be given as rescue medication.
  • Cyclophosphamide — DRUG
    Cyclophosphamide 750 mg/m\^2 administered IV on Day 1 of each 21-day cycle
  • Doxorubicin — DRUG
    Doxorubicin 50 mg/m\^2 administered IV on Day 1 of each 21-day cycle
  • Vincristine — DRUG
    Vincristine 1.4 mg/m\^2 administered by IV push on Day 1 of each 21-day cycle with a recommended cap of 2 mg
  • Prednisone — DRUG
    Prednisone 100 mg/day orally on Days 1-5 (prednisone on Day 1 may be administered IV, with the remaining doses on Days 2-5 to be administered orally) of each 21-day cycle
  • Polatuzumab vedotin — DRUG
    Polatuzumab vedotin 1.8 mg/kg administered IV on Day 1 of each 21-day cycle

Study Details

This is a phase 1B, multi-center, dose-finding study of glofitamab administered in combination with obinutuzumab (Gazyva; \[G\]), rituximab (R) and standard doses of CHOP (G/R-CHOP or R-CHOP) in participants with r/r NHL and G/R CHOP or Pola-R-CHP in participants with untreated diffuse large B-cell lymphoma (DLBCL). Evaluating the safety, preliminary activity, pharmacokinetic (PK), and pharmacodynamic effects of this combination will be the main objectives of this study. The study is divided in two parts: * Part I: Dose finding in participants with r/r NHL; test use of G vs R in Cycle 1 * Part II: Dose Expansion. The maximum tolerated dose or optimal biological dose (MTD or OBD) will be further assessed in participants with untreated DLBCL (\>18 years of age with an age-adjusted International Prognostic Index (IPI) of 2-5). Glofitamab will be studied in combination with R-CHOP and Pola-R-CHP.

Key Dates

Start date
Mar 13, 2018
Status verified
Jan 2025
Primary completion
Dec 2, 2024
Completion
Dec 2, 2024

Study Design

Enrollment
111 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Part 1: Dose Escalation r/r NHL
    Dose finding in participants with r/r NHL: the study will explore different doses of glofitamab in the induction period, starting at a dose of 70 mcg administered in combination with standard of care doses of G/R CHOP and R-CHOP every 3 weeks (Q3W). Participants with r/r NHL will receive 6 cycles of induction treatment (G/R-CHOP). Glofitamab will be administered using step-up dosing for Cycle 2 on Days 8 and 15, followed by single doses on Day 8 for Cycles 3-6. Participants who achieve a complete response (CR), partial response (PR), or stable disease (SD) at the end of induction (EOInd) may optionally receive post-induction treatment (referred to as maintenance) with glofitamab alone. The use of G versus R in Cycle 1 will be compared in parallel dose escalation cohorts.
  • Experimental: Part 2: DLBCL G/R-CHOP
    Participants with untreated DLBCL will receive G-CHOP or R-CHOP in Cycle 1, followed by G/R-CHOP + glofitamab for subsequent cycles. Glofitamab will be administered using step-up dosing for Cycle 2 on Days 8 and 15, followed by single doses on Day 8 for Cycles 3-6 (up to 8). The starting dose of glofitamab for each arm may be one or more levels below the MTD/OBD determined in Part I.
  • Experimental: Part 2: DLBCL Pola-R-CHP
    Participants with untreated DLBCL will receive Pola-R-CHP + glofitamab on Day 1 of each 21-day cycle for a maximum of 6 cycles. Glofitamab will be administered using step-up dosing for Cycle 2 on Days 8 and 15, followed by single doses on Day 8 for Cycles 3-6. The starting dose of glofitamab for each arm may be one or more levels below the MTD/OBD determined in Part I.

Primary Outcome Measure

Part I: Percentage of Participants with Dose Limiting Toxicities (DLTs) [ Time Frame: Up to 29 months ]

Locations (3)

FacilityCityStateZIPSite coordinators
University of Alabama Medical CenterBirminghamAlabama35294-
Levine Cancer InstituteCharlotteNorth Carolina28204-
Fox Chase-Temple Cancer CenterPhiladelphiaPennsylvania19111-

Find similar trials in Birmingham, AL

By research site
University of Alabama Medical Center· Birmingham, ALLevine Cancer Institute· Charlotte, NCFox Chase-Temple Cancer Center· Philadelphia, PA

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