Non-Hodgkin Lymphom

NHL 15B

NHL 15B

Phase II single-arm „window-of-opportunity“ study of a combination of obinutuzumab (GA-101) and venetoclax (ABT-199) in relapsed or refractory diffuse large B-cell lymphoma (DLBCL)

Synopsis

Short title: AGMT_NHL-15B

Title: Phase II single-arm „window-of-opportunity“ study of a combination of obinutuzumab (GA-101) and venetoclax (ABT-199) in relapsed or refractory diffuse large B-cell lymphoma (DLBCL)

Status: open

Start: January 2017

Coordinating Investigator: Univ. Prof. Dr. Ulrich Jäger

EudraCT Number: 2016-001760-10

ClinicalTrialsID: NCT02987400

Number of patients: 21

Sponsor: AGMT gemeinnützige GmbH

Design

Obinutuzumab is given i.v. at a dose of 1000 mg on days 1, 8, 15 in cycle 1 and on day 1 of each following cycle. Venetoclax is given at 800mg daily p.o. One cycle is 21 days. This combination treatment is repeated for up to 3 cycles. Eligible patients will then proceed to stem cell transplantation (in some patients stem cells were already harvested successfully).

A 9 cycles (27 weeks) maintenance phase with obinutuzumab and venetoclax will be given in patients ineligible for transplant.

The study had a 6 patient run-in phase to determine safety and to adjust treatment. A futility analysis is conducted when the first 10 patients have been evaluated for response: If at least two patients had an objective response (CR or PR) the study will be continued.

Primary objective:
  • To evaluate clinical activity and tolerability of obinutuzumab in combination with venetoclax in patients with relapsed/refractory DLBCL
Secondary objectives:
  • Safety: Incidence of dose-limiting toxicities of the combination treatment.
  • Response duration (from first documented response)
  • Progression-free survival
  • Overall survival
  • Ability to proceed to further stem cell transplantation (assessed by number of eligible
  • patients reaching transplant)
  • Identification of genetically/biomarker defined subgroups regarding response and survival

Inclusion/Exclusion criteria

Inclusion criteria (selected):
  • Patients ≥ 18 years of age
  • Diffuse large B-cell lymphoma (DLBCL)
    • with histologically confirmed relapse within 12 months after having achieved a PR or CR with initial R-anthracycline containing therapy, or
    • with refractoriness to initial R-anthracycline containing therapy (not achieving at least a partial response)
  • At least one bi-dimensionally measurable lesion on CT scan defined as > 1.5 cm in its longest dimension
  • ECOG Performance Status of 0, 1, or 2
  • Adequate organ function
Exclusion criteria (selected):
  • DLBCL transformed from other malignancies or CD20 negative DLBCL
  • Radiation, chemotherapy, or immunotherapy or any other anti-cancer therapy ≤ 4 weeks prior to Cycle 1 Day 1
  • Ongoing corticosteroid use > 30 mg/day of prednisone or equivalent
  • Acute or uncontrolled chronic infections
  • Presence of positive test results for Hepatitis B, Hepatitis C and CMV
  • Any sensory or motor peripheral neuropathy greater than or equal to Grade 2

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