Ensayos clínicos

Inclusion Criteria:

Phase 1:

• For dose escalation cohorts, patients with confirmed selected CD38+ hematological malignancies as specified below who have progressed on after standard therapy or for whom there is no effective standard therapy (refractory/relapsed patients). B-cell Non-Hodgkin-lymphoma/leukemia (NHL) patients having at least 1 measurable lesion. Multiple myeloma (MM) patients with measurable M-protein serum and/or 24-hour urine. Acute myeloid leukemia (AML) patients, all types except M3 based on French-American-British (FAB) classification. Acute Lymphoblastic Leukemia (B-cell ALL) patients. Chronic lymphocytic leukemia (CLL) patients.
• For expansion cohorts, patients with relapsed/refractory MM with measurable M-protein (serum M-protein of >0.5 g/dL and/or urine M-protein of >200 mg (24-hr urine)) or elevated serum free light chains (FLC) >10 mg/dL with abnormal FLC ratio) who have progressed on or after standard therapy that includes an iMiD and a proteasome inhibitor and who meet the protocol defined criteria for standard risk or high risk.

Phase 2:

• Patients must have a known diagnosis of multiple myeloma with evidence of measurable disease, and have evidence of disease progression based on International Myeloma Working Group (IMWG) criteria: Serum M-protein ≥1 g/dL, or urine M-protein ≥200 mg/24 hours or in the absence of measurable m-protein, serum FLC ≥10 mg/dL, and abnormal serum immunoglobulin kappa lambda FLC ratio (<0.26 or >1.65).
• Patients must have received at least three prior lines of therapy for MM and must include treatment with an Immunomodulatory drug (IMiD) (for ≥2 cycles or ≥2 months of treatment) and a proteasome inhibitor (PI) (for ≥2 cycles or ≥2 months of treatment) OR patients whose disease is double refractory to an IMiD and a PI. For patients who have received more than 1 type of IMiD and PI, their disease must be refractory to the most recent one.
• Patients must have achieved a minimal response or better to at least one prior line of therapy.
• Patients must have received an alkylating agent (≥2 cycles or ≥2 months) either alone or in combination with other MM treatments.
• Stage 2 only: Patients must have evidence of disease progression on or after the most recent prior regimen based on IMWG criteria.

Exclusion Criteria:

Phase 1:

• Karnofsky performance status <60
• Poor bone marrow reserve
• Poor organ function
• Known intolerance to infused protein products, sucrose, histidine, polysorbate 80 or known hypersensitivity to any of the components of the study therapy that is not amenable to pre-medication with steroids and H2 blockers
• Any serious active disease (including clinically significant infection that is chronic, recurrent, or active) or co-morbid condition, which, in the opinion of the investigator, could interfere with the safety, the compliance with the study or with the interpretation of the results
• Any severe underlying medical conditions including presence of laboratory abnormalities, which could impair the ability to participate in the study or the interpretation of its results

Phase 2:

• Patients with multiple myeloma immunoglobulin M (IgM) subtype
• Previous treatment with any anti-CD38 therapy
• Patients with concurrent plasma cell leukemia
• Patients with known or suspected amyloidosis
• Karnofsky performance status <60 (stage 1)/ECOG Performance status >2 (stage 2).
• Poor bone marrow reserve
• Poor organ function
• Known intolerance to infused protein products, sucrose, histidine, polysorbate 80 or known hypersensitivity to any of the components of the study therapy that is not amenable to pre-medication with steroids and H2 blockers
• Any serious active disease (including clinically significant infection that is chronic, recurrent, or active) or co-morbid condition, which, in the opinion of the investigator, could interfere with the safety, the compliance with the study or with the interpretation of the results
• Any severe underlying medical conditions including presence of laboratory abnormalities, which could impair the ability to participate in the study or the interpretation of its results