Studientherapie

Prephase/Debulking Phase
There will be a mandatory prednisolon prephase of 5 days. Prednisolon will be administered p.o. at a dose of 100 mg for 5 days before the start of the study. If p.o. application is not possible intravenous application is considered equivalent. The prephase can have started before enrollment. Vincristine, as used in other prephases, should not be administered.

Step-up cycle (cycle 1) will comprise of intravenous (i.v.) application of rituximab 375mg/m2 on d1 followed by i.v. application obinutuzumab 1000 mg on d2, followed by i.v. application polatuzumab 1.8mg/kg on d3 and i.v. application of glofitamab in an escalating dose of 2,5 mg on d8 and 10 mg on d15.

Target dose phase (cycle 2-6) will start 3 weeks after the step-up cycle and will be repeated q3w. Each of the 5 cycle comprises rituximab 375mg/m2 and polatuzumab 1.8mg/kg both administered i.v. on d1 and i.v. glofitamab 30 mg on d2

Maintainance phase (cycle 7-12) will start 3 weeks after the last target dose cycle and will comprise 6 cycles of glofitamab 30 mg administered intravenously on d1.

The total duration of the combination of rituximab, obinutuzumab plus polatuzumab and glofitamab will be 6 cycles q3w in 18 weeks (4.5 months) followed by 6 cycles q3w of glofitamab maintenance for 18 weeks ( 4.5 months). In total, there will be 6 doses of rituximab, 6 doses of polatuzumab vedotin, 1 dose of obinutuzumab and 12 doses of glofitamab. An antiinfective prophylaxis using acciclovir, cotrimoxaxol, ciprofloxacin will be mandatory.

Studienstatus

Rekrutierung gestartet/nimmt Patienten auf

Allgemeine Infos zum Antrag

Herr Prof. Dr. med. Björn Chapuy
bjoern.chapuy@charite.de

Charité – Universitätsmedizin Berlin - CBF (Prüfzentrum (CAR-T), 12143)
Medizinische Klinik mit Schwerpunkt Hämatologie und Onkologie
Hindenburgdamm 30
12200 Berlin

The primary objective of this study is:

(1) The 1-year PFS of the chemotherapy-light combination of rituximab, glofitamab, polatuzumab in patients with previously untreated CD20 positive aggressive lymphoma e 80 years of age (cohort 1), and;

(2) The 1-year PFS patients of unfit patients not eligible for R-CHOP-like therapies between 61-79 years of age (cohort 2).

The secondary objectives are to evaluate the feasibility, safety and efficacy, treatment compliance, and patient-reported symptoms of the chemotherapy-light new combination therapy in the first-line treatment of patients with CD20-positive aggressive lymphoma.

All previously not treated patients diagnosed with a histologically confirmed CD20 positive aggressive lymphoma above e 80 years of age (cohort 1) and non-fit patients not eligible for full dosed R-CHOP-like therapies between 61-80 years of age (cohort 2).

n=80 analyzable patients will be included into the trial.

It is assumed that 50 patients are recruited in cohort 1 (e80 years) and 20 patients are recruited in cohort 2 (non-fit patients 61-79 years). The numbers might be subject to changes according to clinical routine.

To accomplish allocation of 70 analyzable patients, a total number of n=100 subjects will be assessed for eligibility and 80 will be enrolled in the trial allowing to compensate for screening failures and drop-outs.

1.) PFS at 1 year for patients e80 years (cohort 1)
2.) PFS at 1 year for non-fit patients 61-79 years (cohort 2)

All secondary endpoints will be evaluated in both cohorts separately.
• Rate of complete metabolic remission (CR) after 6 cycles and at
end of treatment (12 cycles)
• Rate of partial remission (PR) after 6 cycles and at the end of
treatment (12 cycles)
• Overall response rate (ORR; CR+PR)
• Rate of progressive disease (PD)
• Relapse rate
• Conversion rate of PRs to CRs during maintenance
• Rate of treatment-related mortality
• Rate and type of AEs and SAEs as secondary toxicity endpoints.
• Event-free and overall survival at 1 year (EFS and OS; next
lymphoma therapy as an event; non mCR as event)
• Duration of response
• Patient characteristics of recruited population (Ratio: >80/60-79)
• Protocol adherence
• Patient-reported outcome analysis for quality of life
• As determined by imaging and liquid biopsy:
-Percentage of MRD-negative patients at the end of cycle 6 and end of glofitamab
maintainance cycle 12
-Duration of molecular remission as determined by liquid biopsy for MRD negative
patients from end target dose cycles
-Molecular and imaging based predictors of response and sensitivity
-Molecular and imaging based predictors of PR to CR conversion.

Spezifische Infos zum Antrag

s. synposis enclosed

s. synposis enclosed

s. synposis enclosed

30 international, 24 in Germany, 6 in Austria. Inpatient service is mandatory.

Klassische IIT. IKF ist Sponsor und für die Gesamtfinanzierung verantwortlich. Roche ist Unterstützer (IMP+finanziell),

8 Millionen Euro

0

Fees for study set up, archiving and documentation and conducting the PET/CTs will be covered

Ja

• Study synposis
   
• Interessensbekundung und Vertraulichkeitserklärung