REMoDL-B

Trial Overview

A randomised evaluation of molecular guided therapy for Diffuse Large B-Cell Lymphoma with Borteziomib

Inclusion criteria

* Histologically confirmed DLBCL, expressing CD20. Sufficient diagnostic material should be available to forward to HMDS for gene expression profiling and central pathology review. Core biopsies are acceptable, however the molecular profiling success rate is inferior compared to larger surgically acquired tissue samples. Best diagnostic practice encourages investigators to seek the latter approach whenever clinically appropriate.

* Not previously treated for lymphoma and fit enough to receive combination chemoimmunotherapy with curative intent.

* Age >18 years

* Stage IAX (bulk defined as lymph node diameter >10cm) to stage IV disease and deemed to require a full course of chemotherapy

* ECOG performance status 0-2

* Adequate bone marrow function with platelets >100×109/L; neutrophils >1.0×109/L at study entry, unless lower figures are attributable to lymphoma.

* Serum creatinine <150μmol/L, measured or calculated creatinine clearance >30mls/min, serum bilirubin <35μmol/L and transaminases <2.5x upper limit of normal at the time of study entry, unless attributable to lymphoma. * Cardiac function sufficient to tolerate 300mg/m2 of doxorubicin. A pre-treatment echocardiogram is not mandated, but recommended in patients considered at higher risk of anthracycline cardiotoxicity * No concurrent uncontrolled medical condition. * Life expectancy >3 months

* Adequate contraceptive precautions for all patients of child bearing potential

* A negative serum pregnancy test for females of child bearing potential or those <2 years after the onset of the menopause

* Patients will have provided written informed consent

Exclusion criteria

Patients will be excluded from study entry if any of the following criteria are met

* Previous history of treated or untreated indolent lymphoma. However newly diagnosed patients with DLBCL who are found to also have small cell infiltration of the bone marrow or other diagnostic material (discordant lymphoma) will be eligible.

* Uncontrolled systemic infection

* History of cardiac failure of uncontrolled angina

* Clinical CNS involvement

* Serological positivity for Hepatitis C, B or known HIV infection. Viral serological testing is not mandated for study entry, but considered standard of care. Patients who are HepBsAg positive will not be eligible.

* Serious medical or psychiatric illness likely to affect participation or that may compromise the ability to give informed consent.

* Active malignancy other than fully excised squamous or basal cell carcinoma of the skin or carcinoma in situ of the uterine cervix in the preceding 5 years.

* History of allergic reaction to substances containing boron or mannitol

* Patient unwilling to abstain from green tea and preparations made from green tea as bortezomib may interact with these.

* Any co-existing medical or psychological condition that would compromise ability to give informed consent.

* Previous history of treated or untreated indolent lymphoma. However newly diagnosed patients with DLBCL who are found to also have small cell infiltration of the bone marrow or other diagnostic material (discordant lymphoma) will be eligible.

* Uncontrolled systemic infection

* History of cardiac failure of uncontrolled angina

* Clinical CNS involvement

* Serological positivity for Hepatitis C, B or known HIV infection. Viral serological testing is not mandated for study entry, but considered standard of care. Patients who are HepBsAg positive will not be eligible.

* Serious medical or psychiatric illness likely to affect participation or that may compromise the ability to give informed consent.

* Active malignancy other than fully excised squamous or basal cell carcinoma of the skin or carcinoma in situ of the uterine cervix in the preceding 5 years.

* History of allergic reaction to substances containing boron or mannitol

* Patient unwilling to abstain from green tea and preparations made from green tea as bortezomib may interact with these.

* Any co-existing medical or psychological condition that would compromise ability to give informed consent.

Consultant Haematologist

Dr Rod Johnson

Tel: 0113 2068133/2068369

E-mail: [email protected]

Research Nurse

Amy Humphries

Tel: 0113 2068984

E-mail: [email protected]

Other trials currently active for Diffuse Large B-Cell Lymphoma

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SADAL

b Open-label, Randomized Two-arm Study of

Selinexor (KPT-330) with Low Dose Dexamethasone in Patients with Relapsed /

Refractory Diffuse Large B-Cell Lymphoma(DLBCL)

A Phase 2

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