Phase 1/2 Dose Escalation and Efficacy Study of Anti-CD38 Monoclonal Antibody in Patients with Selected CD38+ Hematological Malignancies

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 248

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) 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 mprotein, serum FLC =10 mg/dL, and abnormal serum immunoglobulin kappa
lambda FLC ratio.
- 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 124
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 124

Exclusion Criteria

Phase 1:
- Karnofsky performance status <60
- Poor bone marrow reserve
- Poor organ function
- Known intolerance/hypersensitivity to infused protein products, sucrose or polysorbate 80
- 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 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
- Poor bone marrow reserve
- Poor organ function
- Known intolerance/hypersensitivity to infused protein products, sucrose or polysorbate 80
- 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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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