SAKK 38/19 Assessing a ctDNA and PET-oriented therapy in patients with DLBCL A multicenter, open-label, phase II trial
Indication :

Lymphome diffus à grandes cellules B


Sponsor :

SAKK


Phase :

II


Ligne :

première


Traitement :

Rituximab + cyclophosphamide+doxorubucin+vincristine+prednisone vs Acalabrutinib + Rituximab + cyclophosphamide+doxorubucin+vincristine+prednisone


Site :

CHUV


Contact(s) :
Anne Cairoli
Investigateur Principale

CHUV
Service d'Hématologie

Rue du Bugnon 46
Lausanne
1011

021 314 41 82
anne.cairoli@chuv.ch

Primary objective :

 Assessing the efficacy of acalabrutinib-R-CHOP in DLBCL harboring MYD88 L265P and/or CD79A/B mutations (cohort A)
 Assessing the activity of treatment escalation to acalabrutinib-R-CHOP followed by acalabrutinib monotherapy in DLBCL patients who are double positive: PET/CT positive (Deauville score 4) and no molecular response (<2log10 fold reduction) after two courses of R-CHOP (cohort B)
 Exploring the feasibility of treatment de-escalation to 4 total R-CHOP courses plus two infusions of single agent rituximab in patients lacking both MYD88 L265P and CD79A/B mutations and quickly obtaining both negative PET/CT (Deauville score 1-3) and molecular response (>2log10 reduction of ctDNA) after two cycles of R-CHOP, which further improve to Deauville score 1-2 and absence of ctDNA after two additional RCHOP courses (cohort C).
 Exploring clinical implications of having a negative PET/CT (Deauville score 1-3) but no molecular response (<2log10 reduction of ctDNA) vs a positive PET/CT (Deauville score 4) but molecular response (>2log10 reduction of ctDNA) after two R-CHOP courses (cohort D)


Inclusion criteria :

 Histologically confirmed, treatment-naïve DLBCL, NOS that fulfill all the following:

  • Patient eligible for 6 cycles of R-CHOP
  • Ann Arbor stage I-IV
  • Metabolically active measurable disease by 18FDG PET-CT
  • No previous treatment with systemic chemotherapy or radiotherapy (a pre-phase treatment with steroids for 10 days is allowed after PET/CT and baseline liquid biopsy have been collected)
  • At least 1 measurable site of disease according to Revised Response Criteria for Malignant Lymphoma. The site of disease must be greater than 1.5 cm in the long axis regardless of short axis measurement or greater than 1.0 cm in the short axis regardless of long axis measurement, and clearly measurable in 2 perpendicular dimensions.
  • Quantifiable and qualifiable circulating tumor DNA
     Patients with a prior malignancy and treated with curative intention are eligible if all treatment of that malignancy was completed at least 2 years before registration and the patient has no evidence of disease at registration. Less than 2 years is acceptable for malignancies with low risk of recurrence and/or no late recurrence.
     Adequate bone marrow, hepatic renal, cardiac and coagulation function

Exclusion criteria :

 CNS lymphoma involvement
 Specific diagnostic categories of large B-cell lymphoma such as high grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, primary central nervous system lymphoma, T-cell/histiocyte-rich large Bcell lymphoma, intravascular large B-cell lymphoma, plasmablastic lymphoma, lymphomatoid granulomatosis, primary effusion lymphoma etc.
 Requires or receiving anticoagulation with warfarin or equivalent antagonists (eg, phenprocoumon), ‘dual’ antiplatelet therapy (DAPT), such as aspirin and clopidogrel. However, use of therapeutic low
molecule weight heparin, direct oral anticoagulants, or low dose antiplatelet agents is allowed.
 Concomitant treatment to Acalabrutinib with strong or moderate CYP3A inducers or inhibitors and co-administration with proton pump inhibitors (PPIs).