An Open-label, First-in-human, Dose Escalation Study of SAR440234 Administered as Single Agent by Intravenous Infusion in Patients With Relapsed or Refractory Acute Myeloid Leukemia (R/R AML), B-cell Acute Lymphoblastic Leukemia (B-ALL), or High Risk Myelodysplasia (HR-MDS)

First in Human Testing of Dose-escalation of SAR440234 in Patients With Acute Myeloid Leukemia, Acute Lymphoid Leukemia and Myelodysplastic Syndrome

Sponsors

Lead sponsor: Sanofi

Source Sanofi
Brief Summary

Primary Objective:

- Dose escalation: To determine the maximum tolerated dose (MTD) of SAR440234 administered as a single agent in patients with R/R AML (relapsed or refractory acute myeloid leukemia), HR-MDS (high risk myelodysplastic syndrome), or B-ALL (B-cell acute lymphoblastic leukemia), and determine the recommended phase 2 dose (RP2D) for the subsequent Expansion part.

- Expansion part: To assess the activity of single agent SAR440234 at the RP2D in patients with R/R AML or HR-MDS.

Secondary Objective:

- To characterize the safety profile including cumulative adverse drug reactions.

- To evaluate the potential immunogenicity of SAR440234.

- To assess any preliminary evidence of hematologic response in the Dose Escalation Part.

Detailed Description

The duration of the study for the patients will include a period for screening of up to 14 days. The cycle duration is 42 days. Patients will continue study treatment as long as clinical benefit is possible or until disease progression, unacceptable adverse reaction, patient's decision to stop treatment, or other reason of discontinuation. After study treatment discontinuation patients will return to the study site 30 days after the last administration of SAR440234 for end of treatment assessments. Patients without documented disease progression at the end of a treatment visit who have not yet started treatment with another anti-cancer therapy will proceed with monthly follow-up visits until initiation of another anti-cancer therapy, disease progression, or study cut-off date, whichever comes first.

Overall Status Recruiting
Start Date October 24, 2018
Completion Date November 2022
Primary Completion Date November 2022
Phase Phase 1/Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Incidence of Dose-limiting toxicities (DLTs) Baseline to Day 42
Incidence of allergic reactions/hypersensitivity and CRS/acute infusion reactions Baseline to 30 days after last study treatment administration
Overall response rate (ORR) Baseline to 30 days after last study treatment administration
Duration of response (DOR) Baseline to date of first documentation of disease progression
Event-free survival Baseline to date of first documentation of disease progression
Secondary Outcome
Measure Time Frame
Adverse events Baseline to 30 days after last study treatment administration
Preliminary Anti-leukemia Activity Baseline to approximately 3 months after the last entered patient
Immunogenicity of SAR440234 Baseline to approximately 3 months after the last entered patient
Enrollment 77
Condition
Intervention

Intervention type: Drug

Intervention name: SAR440234

Description: Pharmaceutical form:lyophilisate to be resuspended in solution Route of administration: intravenous

Arm group label: SAR440234

Eligibility

Criteria:

Inclusion criteria :

- Confirmed diagnosis of Acute Myeloblastic leukemia (AML) (except acute promyelocytic leukemia), or myelodysplastic syndrome (MDS) with a risk category of intermediate or higher. Patients must have exhausted available treatment options and must not be eligible for any treatment known to provide clinical benefit.

- Patients with AML must have relapsed or refractory disease that has been resistant to available therapies.

- Patients with B-ALL (B acute lymphoid leukemia) in second or subsequent relapse: should have completed previously ≥1 cycle of a salvage regimen. Patients must have exhausted available treatment options and must not be eligible for any treatment known to provide clinical benefit.

- Patients with HR-MDS (high risk myelodysplastic syndrome) must have >10% blasts in the bone marrow at the time of enrollment and fit one of the following categories: Not eligible for induction therapy and having completed ≥2 cycles of therapy or not eligible for allogeneic stem cell transplant and having completed ≥1 course of induction therapy.

- Signed written informed consent.

Exclusion criteria:

- Age <16 years old.

- Eastern Cooperative Oncology Group (ECOG) performance status >2.

- Patients with inadequate biological tests.

- White blood cell count > 30,000/mm3

- History of active or chronic autoimmune conditions that has required or requires therapy.

- Graft-versus-host disease following allogeneic stem cell transplantation requiring treatment with more than 10 mg of oral prednisone or equivalent daily. The stem cell transplant and/or donor lymphocyte infusion should have been performed more than 3 months before study treatment start.

- Second primary malignancy that requires active therapy. Adjuvant hormonal therapy is allowed.

- Previous treatment with radiotherapy or immunotherapeutic agents in the 4 weeks prior to investigational medicinal product (IMP) administration.

- Previous treatment with any other investigational agent in the 4 weeks prior to IMP administration.

- Receiving, at the time of first IMP administration, of concurrent steroids >10 mg/day of oral prednisone or the equivalent for ≥3 months.

- Requirement for tocilizumab for any other diagnosis.

- Evidence of active central nervous system leukemia at the time of enrollment.

- Acquired immunodeficiency syndrome (AIDS-related illnesses) or HIV (human immunodeficiency virus) disease requiring antiretroviral treatment or having active Hepatitis B viral infection or Hepatitis C viral infection.

- Women of childbearing potential, male with a partner of childbearing potential who do not agree to use effective methods of birth control.

- Any clinically significant, uncontrolled medical conditions that, in the Investigator's opinion, would expose excessive risk to the patient or may interfere with compliance or interpretation of the study results.

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

Gender: All

Minimum age: 16 Years

Maximum age: N/A

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Clinical Sciences & Operations Study Director Sanofi
Overall Contact

Last name: Trial Transparency email recommended (Toll free number for US & Canada)

Phone: 800-633-1610

Phone ext: 1 then #

Email: [email protected]

Location
facility status
Investigational Site Number 8400001 | Houston, Texas, 77030, United States Recruiting
Investigational Site Number 2500004 | Marseille, 13273, France Recruiting
Investigational Site Number 2500001 | Paris Cedex 10, 75010, France Recruiting
Investigational Site Number 2500003 | Villejuif Cedex, 94805, France Recruiting
Location Countries

France

United States

Verification Date

February 2020

Responsible Party

Responsible party type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Arm group label: SAR440234

Arm group type: Experimental

Description: SAR440234 as weekly intravenous injection; a cycle is defined as 6 weeks of study treatment; (Additionally infusion on day 4 is planned for dose level ≥ 3). One dose escalation scheme will be used. Treatment may be continued as long as it is clinically beneficial.

Patient Data Yes
Study Design Info

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov