BI-1206 and an Anti-CD20 Antibody in Patients With CD32b Positive B-cell Lymphoma or Leukaemia

Inclusion Criteria

• Written (signed and dated) informed consent and be capable of co-operating with treatment and follow-up.
• B-cell lymphoma or CLL proven by histology or flow cytometry, relapsed or refractory to conventional treatment, or for which no conventional therapy exists or is declined by the patient. Patients should have received at least one line of conventional previous therapy which must have included a rituximab based regimen.
• CD32b positive malignancy as demonstrated centrally by immunohistochemistry or flow cytometry prior to study entry. Available tissue or blood must have been taken within six months of study entry.
• Life expectancy of at least 12 weeks.
• World Health Organisation (WHO) performance status of 0-2 (Appendix 1).
• Haematological and biochemical indices within the ranges shown below. These measurements must be performed within one week before their first dose of mAb (BI-1206 and/or rituximab) as part of this study.

Laboratory Test Value required

Haemoglobin (Hb) ≥9.0 g/dL (red cell support is permissible)

Absolute neutrophil count (ANC) ≥1.0 x 10^9/L (or >0.5 x 10^9/L if due to lymphoma), granulocyte - colony stimulating factor (G-CSF) support is not permissible at screening

Platelet count ≥50 x 10^9/L (or ≥30 x 10^9/L if due to malignant involvement of bone marrow)

Either:

Serum bilirubin ≤1.5 x upper limit of normal (ULN) unless raised due to Gilbert's syndrome in which case up to 3 x ULN is permissible.

Or:

Alanine amino-transferase (ALT) and /or aspartate amino-transferase (AST) ≤ 2.5 x ULN unless raised due to malignant hepatic involvement in which case up to 5 x ULN is permissible

Either:

Calculated creatinine clearance (Cockcroft Gault) ≥30 mL/min (uncorrected value)

Or:

Isotope clearance measurement ≥30 mL/min (corrected)

• 18 years or over.
• B-cell lymphoma patients only: patients has at least one measurable lesion by CT scan (defined as greater than 1.5 cm in one axis) or in the case of Waldenström's macroglobulinemia, disease must be assessable by the criteria stated in Appendix 6 of the protocol.
• Patients recruited to Arm 2 in Parts A and B (combination arms) only: CD20 positive malignancy as demonstrated by immunohistochemistry or flow cytometry prior to trial entry.

Exclusion Criteria

• Allogenic bone marrow transplant within 12 months prior to the first dose of BI-1206 or presence of chronic graft versus host disease.
• Patients with clinically active leptomeningeal or central nervous system lymphoma/leukaemia.
• Doses of prednisolone >10 mg daily (or equipotent doses of other corticosteroids) are not permitted whilst on the study other than as pre-medication. During the screening period, doses of up to 20 mg per day may be given but the dose must be reduced to 10 mg/day by Cycle 1 Day 1 (or Day -7 in the CLL combination expansion).
• Known or suspected hypersensitivity to study drugs.
• Cardiac or renal amyloid light-chain (AL) amyloidosis.
• Radiotherapy, endocrine therapy, immunotherapy, chemotherapy or investigational medicinal products during the previous 4 weeks before treatment.
• Ongoing toxic manifestations of previous treatments. Exceptions to this are alopecia or certain Grade 1 toxicities, which in the opinion of the Investigator and the Sponsor should not exclude the patient.
• Ability to become pregnant (or already pregnant or lactating). However, those female patients who have a negative serum or urine pregnancy test before enrolment and agree to use two forms of contraception (one highly effective form plus a barrier method) [oral, injected or implanted hormonal contraception and condom; intra-uterine device and condom; diaphragm with spermicidal gel and condom] or agree to sexual abstinence^4 for four weeks before entering the trial, during the trial and for twelve months after completing treatment are considered eligible.
• Male patients with partners of child-bearing potential (unless they agree to take measures not to