Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

SAR650984 (Isatuximab), Lenalidomide, and Dexamethasone in Combination in RRMM Patients

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01749969
First received: December 10, 2012
Last updated: April 26, 2016
Last verified: April 2016
  Purpose

Primary Objectives:

  • To determine the maximum tolerated dose of SAR650984 (isatuximab) with lenalidomide and dexamethasone (LD) in patients with relapsed or refractory multiple myeloma.
  • Expansion Phase Only: To further evaluate preliminary evidence of antitumor activity (objective response rate [ORR]) of SAR650984 (isatuximab) in combination with LD using International Myeloma Working Group (IMWG) criteria.

Secondary Objectives:

  • To evaluate the safety, including immunogenicity, of SAR650984 (isatuximab) in combination with LD in relapsed or refractory multiple myeloma. The severity, frequency and incidence of all toxicities will be assessed.
  • To evaluate the pharmacokinetics (PK) of SAR650984 (isatuximab) when administered in combination with LD and the PK of lenalidomide in combination with SAR650984 and dexamethasone.
  • To assess the relationship between clinical (adverse event [AE] and/or tumor response) effects and pharmacologic parameters (PK/pharmacodynamics), and/or biologic (correlative laboratory) results.
  • For the dose expansion phase, estimate the activity (ORR) using IMWG defined response criteria of SAR650984 (isatuximab) plus LD.
  • To describe progression-free survival (PFS) in patients treated with this combination.

Condition Intervention Phase
Plasma Cell Myeloma
Drug: isatuximab SAR650984
Drug: lenalidomide
Drug: dexamethasone
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1b Study of SAR650984 (Anti-CD38 mAb) in Combination With Lenalidomide and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Number of patients with adverse events when treated with SAR650984 (isatuximab) in combination with LD [ Time Frame: Up to 30 days for patients experiencing progressive disease and continuously while patients are on treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Preliminary assessment of overall response rate [ Time Frame: 9 months from the last investigational medicinal product (IMP)/non-IMP (NIMP) administration ] [ Designated as safety issue: No ]
  • Preliminary assessment of progression-free survival (PFS) [ Time Frame: Up to disease progression ] [ Designated as safety issue: No ]
  • Assessment of PK parameters - maximum concentration (Cmax) [ Time Frame: Up to disease progression plus 60 days ] [ Designated as safety issue: No ]
  • Assessment of PK parameters - time to reach Cmax (Tmax) [ Time Frame: Up to disease progression plus 60 days ] [ Designated as safety issue: No ]
  • Assessment of PK parameters - concentration observed at end of infusion (Ceoi) [ Time Frame: Up to disease progression plus 60 days ] [ Designated as safety issue: No ]
  • Assessment of PK parameters - area under the plasma concentration versus time curve over the dosing interval (AUCtau) [ Time Frame: Up to disease progression plus 60 days ] [ Designated as safety issue: No ]
  • Assessment of PK parameters - plasma concentration observed just before treatment administration during repeated dosing (Ctrough) [ Time Frame: Up to disease progression plus 60 days ] [ Designated as safety issue: No ]
  • Number of CD38 receptors occupied by SAR650984 (isatuximab) [ Time Frame: Up to disease progression plus 60 days ] [ Designated as safety issue: No ]
  • CD38 receptor density [ Time Frame: Up to disease progression plus 60 days ] [ Designated as safety issue: No ]
  • Immunogenicity: Number of anti-SAR650984 (isatuximab) antibodies in response to SAR650984 (isatuximab) [ Time Frame: Up to disease progression plus 60 days ] [ Designated as safety issue: No ]

Enrollment: 57
Study Start Date: February 2013
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SAR650984 (isatuximab)

SAR650984 (isatuximab) (escalating dose) plus lenalidomide 25 mg on Days 1 to 21 plus dexamethasone 40 mg on Days 1, 8, 15, 22 in 28-day cycles for all cohorts up to disease progression.

For Q2W cohorts: SAR650984 (isatuximab) on Days 1 and 15 of every cycle. For QW/Q2W cohorts: SAR650984 (isatuximab) on Days 1, 8, 15, and 22 of first cycle and Days 1 and 15 of every subsequent cycle.

Drug: isatuximab SAR650984
Pharmaceutical form:solution Route of administration: intravenous
Drug: lenalidomide
Pharmaceutical form:capsules Route of administration: oral
Other Name: Revlimid
Drug: dexamethasone
Pharmaceutical form:solution or tablet Route of administration: intravenous or oral

Detailed Description:
The study duration for an individual patient will include a screening period for inclusion of up to 21 days, and at least 4 weeks of treatment in the absence of severe adverse reaction, dose limiting toxicity or disease progression plus up to 60 days post-treatment follow up. The treatment period may continue until disease progression, intolerable toxicity, or Investigator, sponsor, or patient decision to discontinue therapy. After study treatment discontinuation, an end of treatment (EOT) visit will be done at 30 days to assess safety, and at 30 and 60 days for anti-drug antibody (ADA) and PK. If the ADA is positive or inconclusive at day 60, then PK and ADA will be repeated every 30 days until ADA is negative. Patients who discontinue treatment for reasons other than progression of disease will be followed monthly until progression, initiation of subsequent therapy, or until the primary analysis cutoff date, whichever comes first.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

Male or female patients age 18 years or older. Diagnosis of multiple myeloma and documentation of at least 2 prior therapies (induction therapy, autologous stem cell transplant, consolidation and maintenance therapy is considered one prior therapy); there is no maximum number of prior regimens and prior bone marrow transplant is acceptable.

Confirmed evidence of disease progression from immediately prior MM therapy or refractory to the immediately prior therapy.

Patients may have received prior immunomodulatory drugs (IMiDs®) (eg, lenalidomide or thalidomide).

Patients with measurable disease. Patients with a Karnofsky ≥60% performance status. Females of childbearing potential (FCBP). Voluntary written informed consent before performance of any study-related procedure not part of routine medical care with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.

Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local subject privacy regulations).

Able to take aspirin daily as prophylactic anti-coagulation therapy (patients intolerant to aspirin may use warfarin, low molecular weight heparin or equivalent anti-platelet therapy).

Adequate organ function.

Exclusion criteria:

Diagnosed or treated for another malignancy within 3 years prior to enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low risk prostate cancer after curative therapy.

Prior anti-cancer therapy (chemotherapy, targeted agents, radiotherapy, and immunotherapy) within 21 days except for alkylating agents (eg, melphalan) where 28 days will be required or participated in another clinical trial during the past 30 days.

History of significant cardiovascular disease within the past 6 months, unless the disease is well-controlled.

Prior autologous stem cell transplant within 12 weeks of the first dose of study treatment and/or prior allogeneic transplant within 1 year or has evidence of active graft-versus-host disease (GVHD) requiring >10 mg prednisone daily.

Daily requirement for corticosteroids (>10 mg prednisone qd for 7 consecutive days) (except for inhalation corticosteroids and patients being treated for adrenal insufficiency/replacement therapy).

Evidence of mucosal or internal bleeding. Prior radiation therapy or major surgical procedure within 4 weeks of the first dose of study treatment.

Known active infection requiring parenteral or oral anti-infective treatment. Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse follow-up evaluation.

Any medical conditions that, in the Investigator's opinion, would impose excessive risk to the patient.

Hypersensitivity to any of the components of study therapy that is not amenable to premedication with steroids and H2 blockers.

Known human immunodeficiency virus (HIV) or active hepatitis B or C viral infection.

Neuropathy ≥ Grade 3 or painful neuropathy ≥ Grade 2. Gastro-intestinal abnormalities, including bowel obstruction, inability to take oral medication, requirement for intravenous (IV) alimentation, active peptic ulcer or prior surgical procedures or bowel resection affecting absorption.

Pregnancy.

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: NCT01749969

Locations
United States, California
Investigational Site Number 840004
San Francisco, California, United States, 94117
United States, Florida
Investigational Site Number 840001
Tampa, Florida, United States, 33612
United States, Missouri
Investigational Site Number 840002
St Louis, Missouri, United States, 63110
United States, New York
Investigational Site Number 840005
New York, New York, United States, 10021
United States, Ohio
Investigational Site Number 840003
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01749969     History of Changes
Other Study ID Numbers: TCD11863  U1111-1119-3107 
Study First Received: December 10, 2012
Last Updated: April 26, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Lenalidomide
Thalidomide
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal

ClinicalTrials.gov processed this record on September 27, 2016