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

Phase 1

Conditions: Haematological malignancy
MedDRA version: 21.1Level: PTClassification code 10066476Term: Haematological malignancySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2013-001418-13-GB

Lead Sponsor: Sanofi-aventis recherche & développement

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 341

Inclusion Criteria

Phase 1:
-For dose escalation cohorts, patients with confirmed selected CD38+ haematological 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 (=0.5 g/dL in case of IgA disease for stage 2), 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.
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 171
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 170

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.

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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