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

This study is currently recruiting participants.
Verified April 2014 by Sanofi
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01084252
First received: March 9, 2010
Last updated: April 16, 2014
Last verified: April 2014
  Purpose

Primary Objective:

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

Secondary Objectives:

  • 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

Condition Intervention Phase
Hematological Malignancy
Drug: SAR650984
Phase 1

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 ]

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 + 30days, 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 - PK will be assessed at cycle 1, cycle 2 and at the end of treatment during the accelarated phase and cycle 1,2,3,4 and at the end of treatment during the basic phase ] [ Designated as safety issue: No ]
  • Main PD Biomarker : CD38 receptor occupancy [ Time Frame: every 4 weeks up to a maximum duration study duration of 36 months ] [ 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 ]
  • Preliminary activity assessment with criteria depending on type of hematological malignancies [ Time Frame: every 4 weeks, up to end of treatment + 30days ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: June 2010
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SAR650984
Accelerated dose escalation phase (1 patient/cohort), two administrations every two weeks (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. In each cohort, at least 7 days must pass after dosing the first patient before dosing the second patient. Cohort 1-10 will enroll patients with CD38+ hematological malignancies and cohort 11 onwards will enroll patients with multiple myeloma only.
Drug: SAR650984

Pharmaceutical form: solution for infusion

Route of administration: intravenous


Detailed Description:

The study duration for an individual patient will include a period for inclusion of up to 2 weeks, up to 4 weeks of SAR650984 administration (QW, every week or Q2W, every 2 weeks) unless discontinued earlier due to safety or disease progression, followed by 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.

Patients with Stable Disease (SD), or objective response (complete or partial response : CR, PR) and no Dose Limiting toxicity (DLT) at the end of 4 weeks of SAR650984 dosing may continue treatment (upon investigator's decision) as long as clinical benefit is possible, or until progression (PD) or for other reasons . Patients will be followed by 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.

  Eligibility

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

Inclusion criteria:

  • 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) patient
  • Chronic lymphocytic leukemia (CLL) patients

Exclusion criteria:

  • Karnofsky performance status <60
  • Poor bone marrow reserve
  • Poor organ function
  • Known intolerance/hypersensitivity to infused protein products
  • 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
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: April 16, 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 April 16, 2014