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First-in-human Study of SAR443579 Infusion in Male and Female Participants of at Least 12 Years of Age With Relapsed or Refractory Acute Myeloid Leukemia (R/R AML), B-cell Acute Lymphoblastic Leukemia (B-ALL) or High Risk-myelodysplasia (HR-MDS)

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ClinicalTrials.gov Identifier: NCT05086315
Recruitment Status : Recruiting
First Posted : October 20, 2021
Last Update Posted : June 22, 2022
Sponsor:
Information provided by (Responsible Party):
Sanofi

Brief Summary:
This is an open-label, multicenter, Phase 1/Phase 2, dose escalation and dose expansion study to evaluate the safety, pharmacokinetics, pharmacodynamics and anti-leukemic activity of SAR443579 in various hematological malignancies.

Condition or disease Intervention/treatment Phase
Acute Lymphocytic Leukaemia; Acute Myeloid Leukaemia Refractory; Myelodysplastic Syndrome Drug: SAR443579 Phase 1 Phase 2

Detailed Description:
2.5 years.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 82 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, First-in-human, Dose-escalation Study of SAR443579 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)
Actual Study Start Date : December 8, 2021
Estimated Primary Completion Date : June 5, 2024
Estimated Study Completion Date : November 8, 2027


Arm Intervention/treatment
Experimental: SAR443579

Dose Escalation: SAR443579 administered intravenously at escalating dose levels.

Dose Expansion: SAR443579 administered intravenously at the recommended dose and schedule determined from the dose escalation.

Drug: SAR443579
Powder for solution for infusion; by IV infusion




Primary Outcome Measures :
  1. Incidence of dose-limiting toxicity (DLT) (Escalation Part) [ Time Frame: Day 1 to Day 28 ]
  2. Proportion of participants who have a CR (Complete Remission) + CRi (Complete Remission with Incomplete Hematological Recovery) (Expansion Part) [ Time Frame: Up to 3 months ]

Secondary Outcome Measures :
  1. Recommended Phase 2 dose (RP2D) [ Time Frame: Up to 12 months ]
  2. Number of participants with treatment-emergent adverse events (TEAEs) (Escalation and Expansion Parts) [ Time Frame: Up to 30 months ]
  3. Cmax: Maximum observed concentration [ Time Frame: Day 1 to end of trial (maximum up to 30 months) ]
  4. AUC0-T: Area under the concentration versus time curve calculated using the trapezoidal method during a dosing interval (T) [ Time Frame: Day 1 to end of trial (maximum up to 30 months) ]
  5. Incidence of anti-drug antibody (ADA) (Escalation and Expansion Parts) [ Time Frame: Up to 30 months ]
  6. Anti-leukemic activity as define by International Working Group (IWG) for AML (modified) and MDS, or NCCN for B-ALL (Escalation Part) [ Time Frame: Up to 3 months ]
  7. Proportion of participants with CR + CRh (complete remission with partial hematological recovery) (Expansion Part) [ Time Frame: Up to 3 months ]
  8. Rate of CR + CRh + CRi + MLFS (morphological leukemia-free state) (Expansion Part) [ Time Frame: Up to 3 months ]
  9. Time interval from first documented evidence of CR until progressive disease (PD) as per modified IWG or death due to any cause, whichever comes first (Expansion Part) [ Time Frame: Up to 30 months ]
  10. Time interval from date of first SAR443579 administration to induction failure, relapse or death due to any cause, whichever comes first (Expansion Part) [ Time Frame: Up to 30 months ]
  11. Proportion of survivors from the first SAR443579 administration to death from any cause (Expansion Part) [ Time Frame: Up to 12 months ]
  12. Rate of HSCT through SAR443579 treatment but before subsequent therapy (Expansion Part) [ Time Frame: Up to 30 months ]
  13. Time from first SAR443579 administration to discontinuation for any reason excluding remission, ie, disease progression, treatment toxicity, patient preference or death (Expansion Part) [ Time Frame: Up to 30 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

- Participant must be ≥12 years old at the time the trial participant or legal guardian signs the informed consent form.

For participants of the Escalation Part only:

- Confirmed diagnosis of primary or secondary AML [any subtype except acute promyelocytic leukemia (APL)] according to World Health Organization (WHO) classification. Patients with AML must meet one of the following criteria, a), b) or c) and are limited to those with no available (or are ineligible) therapy with known clinical benefit.

a) Primary Induction Failure (PIF) AML, defined as disease refractory to one of the following, i or ii.

i) An intensive induction attempt, per institution. Induction attempts include high-dose and/or standard-dose cytarabine ± an anthracyclines/anthracenedione ± an anti-metabolite, with or without growth factor or targeted therapy containing regimens.

Examples include but are not limited to:

  • One cycle of high dose cytarabine (HiDAC) containing regimen
  • One cycle of liposomal cytarabine and daunorubicin
  • Two cycles of standard dose cytarabine containing regimen ii) For adults who are age 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy; PIF is defined as AML refractory to one of the following less intensive regimens, 1 or 2:

    1. 4 cycles of hypomethylating agents (HMA) or
    2. 2 cycles HMA + venetoclax b) Early relapse (ER) AML, defined as AML in relapse with CR duration < 6 months from most recent treatment c) Leukemia in first or higher relapse

      • Confirmed diagnosis of cluster of differentiation 123 (CD123) + HR-MDS, with a Revised International Prognostic Scoring System (IPSS-R) risk category of intermediate or higher and are limited to those with no available (or are ineligible) therapy with known clinical benefit.
  • Not eligible for induction therapy and having completed ≥2 cycles of any of the following: hypomethylating agent (eg, 5 azacitidine or decitabine) and/or venetoclax, chemotherapy, or targeted agents.
  • Not eligible for autologous stem cell transplant (ASCT) and having completed ≥1 course of induction therapy.

    • Confirmed diagnosis of CD123 + B-ALL without extramedullary lesions that have no available (or are ineligible) therapy with known clinical benefit.

For Participants in the Expansion Part Only:

  • For participants in Cohort A: Participants meeting inclusion criteria for AML patients that have been primary refractory (PIF) to prior induction treatment or who have had ER occurring 6 months or less after an initial remission on prior induction treatment.
  • For participants in Cohort B: Participants meeting inclusion criteria for AML patients that have had late relapse (LR), occurring more than 6 months after an initial remission on prior induction treatment.
  • Body weight >40 kg. -- Body weight >40 kg. - - -

Exclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) performance status >2 (≥18 years-old). Karnovsky Scale (16-17 years-old) <50% or Lansky Scale (<16 years-old) <50%.
  • History of an active or chronic autoimmune condition that has required or requires therapy.
  • Second primary malignancy that requires active therapy. Adjuvant hormonal therapy is allowed.
  • Evidence of active central nervous system leukemia at the time of enrollment as evidenced by cytology or pathology.
  • Known acquired immunodeficiency syndrome (AIDS-related illnesses) or human immunodeficiency virus (HIV) disease requiring antiretroviral treatment, or having active hepatitis B or C infection, or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Participants with a history of SARS-CoV-2 infection must have completed clinical recovery at least 1 month prior to enrollment. - Prior treatment with an anti-CD123-directed agent.
  • Prior HSCT with relapse beyond 3 months may be included only if off immunosuppression for a minimum of 4 weeks and no evidence of graft versus host disease (GVHD).
  • Receiving at the time of first investigational medicinal product (IMP) administration corticosteroid as a concomitant medication with corticosteroid dose >10 mg/day of oral prednisone or the equivalent,
  • Prior treatment with cellular therapy, eg, chimeric antigen receptor T cell (CAR-T) or chimeric antigen receptor NK cell (CAR-NK).
  • Concurrent treatment with other investigational drugs.
  • Radiotherapy, even if palliative in intent, may not be given during the study.
  • Prophylactic use of hematopoietic growth factors (eg, granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), erythropoietin) during the DLT observation period in the Dose Escalation Part only. - Individuals accommodated in an institution because of regulatory or legal order; prisoners or participants who are legally institutionalized.
  • Pregnant and breast-feeding women.
  • History of solid organ transplant, including corneal transplant.
  • Average QTc (using the Fridericia correction calculation) >470 millisecond (msec) at screening.

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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05086315


Contacts
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Contact: Trial Transparency email recommended (Toll free for US & Canada) 800-633-1610 ext option 6 Contact-US@sanofi.com

Locations
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United States, California
Investigational Site Number :8400002 Recruiting
Duarte, California, United States, 91010
United States, Texas
Investigational Site Number :8400001 Recruiting
Houston, Texas, United States, 77030
Australia, Victoria
Investigational Site Number :0360002 Recruiting
Melbourne, Victoria, Australia, 3000
Investigational Site Number :0360001 Recruiting
Melbourne, Victoria, Australia, 3004
Netherlands
Investigational Site Number :5280001 Recruiting
Rotterdam, Netherlands, 3015 GD
Sponsors and Collaborators
Sanofi
Investigators
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Study Director: Clinical Sciences & Operations Sanofi
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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT05086315    
Other Study ID Numbers: TCD17197
U1111-1266-7399 ( Registry Identifier: ICTRP )
2021-004287-98 ( EudraCT Number )
First Posted: October 20, 2021    Key Record Dates
Last Update Posted: June 22, 2022
Last Verified: June 20, 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Myelodysplastic Syndromes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Leukemia, Lymphoid
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases