Dose Escalation Study of Anti-CD38 Monoclonal Antibody in Patients With Selected CD38+ Hematological Malignancies

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Sanofi
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01084252
First received: March 9, 2010
Last updated: July 17, 2014
Last verified: July 2014
  Purpose

Primary Objective:

Phase 1:

To determine the maximum tolerated dose (MTD)/maximum administered dose (MAD) of SAR650984

Phase 2:

To evaluate the activity of single-agent SAR650984 at different doses/schedules and to further evaluate the overall response rate (ORR) of SAR650984 at the selected dose

Secondary Objectives:

Phase 1:

  • To characterize the global safety profile including cumulative toxicities
  • To evaluate the pharmacokinetic (PK) profile of SAR650984 in the proposed dosing schedule(s)
  • To assess the pharmacodynamics, immune response, and preliminary disease response

Phase 2:

  • To evaluate safety of SAR650984
  • To evaluate the efficacy of SAR650984 as measured by duration of response, clinical benefit rate, progression free survival, overall survival
  • To evaluate patient reported outcomes
  • To evaluate the PK profile
  • To evaluate the immunogenicity of SAR650984
  • To investigate the relationship between CD38 receptor occupancy and CD38 receptor density and parameters of clinical response

Condition Intervention Phase
Hematological Malignancy
Drug: SAR650984
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Dose Escalation Safety and Pharmacokinetic Study of Multiple Intravenous Administrations of a Humanized Monoclonal Antibody (SAR650984) Against CD38 In Patients With Selected CD38+ Hematological Malignancies

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Dose Limiting Toxicities (DLTs) [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
  • Overall Response Rate [ Time Frame: 4 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety as assessed from Adverse events reporting, laboratory tests, vital signs according to the National Cancer Institute - Common Toxicity Criteria (NCI-CTC) version 4.0 grade scaling [ Time Frame: end of treatment + 30 days, up to a maximum study duration of 36 months ] [ Designated as safety issue: Yes ]
  • Main PK parameters : Partial area under the serum concentration time curve (AUC), maximum observed concentration (Cmax) [ Time Frame: end of treatment + 60 days ] [ Designated as safety issue: No ]
  • Main PD Biomarker : CD38 receptor density [ Time Frame: end of treatment ] [ Designated as safety issue: No ]
  • Immune response : levels of human anti-human antibodies [ Time Frame: end of treatment + 60 days ] [ Designated as safety issue: Yes ]
  • Duration of Response [ Time Frame: 12 months from last patient in ] [ Designated as safety issue: No ]
  • Patient reported outcomes [ Time Frame: every 4 weeks up to end of treatment ] [ Designated as safety issue: No ]
  • Overall Survival [ Time Frame: 12 months from last patient in ] [ Designated as safety issue: No ]
  • Clinical Benefit Rate [ Time Frame: 12 months from last patient in ] [ Designated as safety issue: No ]
  • Progression Free Survival [ Time Frame: 12 months from last patient in ] [ Designated as safety issue: No ]

Estimated Enrollment: 248
Study Start Date: May 2010
Estimated Study Completion Date: August 2017
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SAR650984

Phase 1: Accelerated dose escalation phase (1 patient/cohort), two administrations every two week (Q2W) per dose cohort. Followed by basic dose escalation phase evaluating SAR650984 administration weekly (QW) and Q2W with 3-6 patients/cohort treated until disease progression or unsatisfactory safety. Cohort 1-10 will enroll patients with CD38+ hematological malignancies and cohort 11 onwards will enroll patients with multiple myeloma only. Two expansion cohorts will evaluate the recommended Phase 2 dose (RP2D) in standard risk and high risk multiple myeloma patients.

Phase 2: Stage 1 will further evaluate three dose levels and schedules in parallel, randomized arms. Arm 1: Dose 1 Q2W, Arm 2: Dose 2 Q2W, Arm 3: Dose 2 Q2W for 8 weeks then every 4 weeks (Q4W). Stage 2 will use the dose and schedule determined from Stage 1.

Drug: SAR650984

Pharmaceutical form: solution for infusion

Route of administration: intravenous


Detailed Description:

The Phase 1 study duration for an individual patient will include a screening period for inclusion of up to 2 weeks, treatment with SAR650984 QW (every week) or Q2W (every 2 weeks) unless discontinued earlier due to safety or disease progression. Patients will be followed for a minimum of 30 days following the last use of study drug or more than 30 days in case of unresolved toxicity, or up to initiation of another anticancer treatment.

The Phase 2 study duration for an individual patient will include a screening period for inclusion of up to 3 weeks, treatment with SAR650984 Q2W or Q4W (every 4 weeks) unless discontinued earlier due to safety or disease progression. Patients will be followed every 3 months following the last use of study drug until death or study cutoff whichever comes first.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 m-protein, 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.

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

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01084252

Contacts
Contact: For site information, send an email with site number to Contact-Us@sanofi.com

Locations
United States, Arizona
Investigational Site Number 840003 Recruiting
Scottsdale, Arizona, United States, 85259-5499
United States, California
Investigational Site Number 840005 Recruiting
San Francisco, California, United States, 94117
United States, Georgia
Investigational Site Number 840009 Recruiting
Atlanta, Georgia, United States, 30322
United States, New Jersey
Investigational Site Number 840011 Recruiting
Hackensack, New Jersey, United States, 07601
United States, Ohio
Investigational Site Number 840004 Completed
Cincinnati, Ohio, United States, 45267-0542
United States, Tennessee
Investigational Site Number 840001 Recruiting
Nashville, Tennessee, United States, 37232
United States, Utah
Investigational Site Number 840002 Recruiting
Salt Lake City, Utah, United States, 84112-5550
United States, Washington
Investigational Site Number 840012 Recruiting
Seattle, Washington, United States, 98109
France
Investigational Site Number 250003 Recruiting
Nantes Cedex 01, France, 44093
Investigational Site Number 250004 Recruiting
Pierre Benite, France, 69310
Investigational Site Number 250001 Recruiting
Toulouse, France, 31052
Spain
Investigational Site Number 724002 Recruiting
Pamplona, Spain, 31008
Investigational Site Number 724001 Recruiting
Salamanca, Spain, 37007
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01084252     History of Changes
Other Study ID Numbers: TED10893, U1111-1116-5472
Study First Received: March 9, 2010
Last Updated: July 17, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Hematologic Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 31, 2014