Single arm NCRI phase II study of CHOP in combination with Ofatumumab in induction and maintenance for patients with newly diagnosed Richter’s syndrome

Eyre, Toby A.; Clifford, Ruth; Roberts, Corran; Boyle, Lucy; Francis, Anne B.; Schuh, Anna; Dutton, Susan

doi:10.1186/s12885-015-1048-9

Cited by 11 publications

(7 citation statements)

References 21 publications

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“…Simon's minimax two-stage design was implemented to calculate the required sample size (n = 35) to identify a desired response of the trial drug of 47% with a power of 80% and significance of 20%. For a detailed description of the study design, patient selection, statistical design, interventions and outcome measures, the reader is directed to the open access protocol manuscript (Eyre et al, 2015).…”

Section: Methodsmentioning

confidence: 99%

NCRI phase II study of CHOP in combination with ofatumumab in induction and maintenance in newly diagnosed Richter syndrome

et al. 2016

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Richter syndrome (RS) is associated with chemotherapy resistance and a poor historical median overall survival (OS) of 8-10 months. We conducted a phase II trial of standard CHOP-21 (cyclophosphamide, doxorubicin, vincristine, prednisolone every 21 d) with ofatumumab induction (Cycle 1: 300 mg day 1, 1000 mg day 8, 1000 mg day 15; Cycles 2-6: 1000 mg day 1) (CHOP-O) followed by 12 months ofatumumab maintenance (1000 mg given 8-weekly for up to six cycles). Forty-three patients were recruited of whom 37 were evaluable. Seventy-three per cent were aged >60 years. Over half of the patients received a fludarabine and cyclophosphamide-based regimen as prior CLL treatment. The overall response rate was 46% (complete response 27%, partial response 19%) at six cycles. The median progression-free survival was 6·2 months (95% confidence interval [CI] 4·9-14·0 months) and median OS was 11·4 months (95% CI 6·4-25·6 months). Treatment-naïve and TP53-intact patients had improved outcomes. Fifteen episodes of neutropenic fever and 46 non-neutropenic infections were observed. There were no treatment-related deaths. Seven patients received platinum-containing salvage at progression, with only one patient obtaining an adequate response to proceed to allogeneic transplantation. CHOP-O with ofatumumab maintenance provides minimal benefit beyond CHOP plus rutuximab. Standard immunochemotherapy for RS remains wholly inadequate for unselected RS. Multinational trials incorporating novel agents are urgently needed.

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Section: Methodsmentioning

confidence: 99%

NCRI phase II study of CHOP in combination with ofatumumab in induction and maintenance in newly diagnosed Richter syndrome

et al. 2016

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“…Accordingly, in vitro studies suggest that ofatumumab activates complement more efficiently than rituximab[117]. An ongoing single arm phase II trial has produced complete or partial responses in several patients receiving CHOP therapy plus ofatumumab for the treatment of Richter's transformation, a transformation of CLL to diffuse large B cell lymphoma[118]. …”

Section: Fc Domain-mediated Activationmentioning

confidence: 99%

Mechanisms of action of therapeutic antibodies for cancer

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Aldeghaither

et al. 2015

Molecular Immunology

142

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The therapeutic utility of antibodies and their derivatives is achieved by various means. The FDA has approved several targeted antibodies that disrupt signaling of various growth factor receptors for the treatment of a number of cancers. Rituximab, and other anti-CD20 monoclonal antibodies are active in B cell malignancies. As more experience has been gained with anti-CD20 monoclonal antibodies, the multifactorial nature of their anti-tumor mechanisms has emerged. Other targeted antibodies function to dampen inhibitory checkpoints. These checkpoint inhibitors have recently achieved dramatic results in several cancers, including melanoma. These and related antibodies continue to be investigated in the clinical and pre-clinical settings. Novel antibody structures that target two or more antigens have also made their way into clinical use. Tumor targeted antibodies can also be conjugated to chemo- or radiotherapeutic agents, or catalytic toxins, as a means to deliver toxic payloads to cancer cells. Here we provide a review of these mechanisms and a discussion of their relevance to current and future clinical applications.

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“…Most data for treatment for RS is derived from single-arm phase I-II studies, and retrospective analyses [13,[72][73][74][75][76][77][78][79]. The standard therapy for RS is chemoimmunotherapy with a median survival after therapy of less than 1 year [36].…”

Section: Treatmentmentioning

confidence: 99%

Histologic transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma

et al. 2016

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Although generally considered a clinically indolent neoplasm, CLL/SLL may undergo transformation to a clinically aggressive lymphoma. The most common form of transformation, to DLBCL, is also known as Richter syndrome. Transformation determines the course of the disease and is associated with unfavorable patient outcome. Precise detection of transformation and identification of predictive biomarkers and specific molecular pathways implicated in the pathobiology of transformation in CLL/SLL will enable personalized therapeutic approach and provide potential avenues for improving the clinical outcome of patients. In this review, we present an overview of the pathologic features, risk factors, and pathogenic mechanisms of CLL/ SLL transformation.

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Single arm NCRI phase II study of CHOP in combination with Ofatumumab in induction and maintenance for patients with newly diagnosed Richter’s syndrome

Cited by 11 publications

References 21 publications

NCRI phase II study of CHOP in combination with ofatumumab in induction and maintenance in newly diagnosed Richter syndrome

NCRI phase II study of CHOP in combination with ofatumumab in induction and maintenance in newly diagnosed Richter syndrome

Mechanisms of action of therapeutic antibodies for cancer

Histologic transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma

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