Clinical Trial 21416

• Overview

  Study Title:

  A Phase 1, Open-label, Preliminary Pharmacokinetics (PK) and Safety Study of CLN-049 (An fms-like tyrosine kinase 3 [FLT3] x cluster of differentiation 3 [CD3] bispecific T cell engager) in Patients with Relapsed/Refractory Acute Myeloid Leukemia (AML)

  Summary:

  CLN-049-001 is a Phase 1, open-label, multicenter, first-in-human trial of CLN-049 in patients with Relapsed/Refractory AML

  Objective:

  1. To assess the safety and tolerability of IV--administered CLN-049; 2. To characterize select pharmacokinetic (PK) parameters associated with IV-administered CLN-049; 3. To evaluate the immunogenicity of CLN-049 and assess potential impact on PK exposure.

• Treatments

  Therapies:

  Therapy (NOS)

  Medications:

  CLN-049 (); Diphenhydramine (); Hydrocortisone (); Paracetamol (); acetaminophen ()

• Inclusion Criteria

  • Males or females aged > 18 years of age
  • Willing and able to give written informed consent and adhere to protocol requirements; written informed consent and any locally required authorization must be obtained from the patient prior to performing any protocol-related procedures, including screening evaluations, and serial samples of bone marrow and peripheral blood
  • Confirmed diagnosis of recurrent or refractory AML as defined below
  • (a) AML either de novo or secondary that either: are in relapse to standard therapy following an initial response or failed primary induction therapy (PIF) with no complete response (CR [failed ≥2 induction attempts]) and for whom no other approved therapy is available
  • (b) For adults 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. Patient has received 2 or more cycles of B-cell lymphoma 2 (bcl-2) inhibitors in combination with azacitidine, decitabine, or low dose cytarabine
  • (c) MDS with 5% blasts that is relapsed after or refractory to hypomethylating agent (HMA) therapy, defined as prior receipt of 4 cycles of HMA therapy with failure to attain a response, or progression of disease or relapse at any time after prior response to HMA therapy.
  • Patient has received, and has progressed, recurred, or is intolerant of approved therapeutic options that are available, or declines treatment with these therapies
  • White blood cell (WBC) count at the time of the first dose is > Eastern Cooperative Oncology Group (ECOG) performance status is 0 to 2.
  • Toxicities related to prior study therapy should have resolved to Grade 1 or less according to criteria of NCI CTCAE v5.0, except for alopecia, lymphopenia, neutropenia, leukopenia, anemia, thrombocytopenia. Patients with chronic but stable toxicities may be allowed to enroll after agreement between the Investigator and Sponsor.
  • The patient's laboratory values meet the criteria per protocol

• Exclusion Criteria

  • Diagnosis of acute promyelocytic leukemia
  • Active central nervous system leukemia. For patients with a history of CNS leukemia, a lumbar puncture should be performed during screening to exclude the presence of active CNS involvement
  • Isolated extramedullary relapse
  • Prior organ allograft
  • Allogeneic hematopoietic transplantation within six months of treatment or with linical or laboratory evidence of GVHD, or requiring ongoing treatment with immune suppression within 2 months of the first dose of CLN-049
  • Treatment with any of the following:
  • Radiation therapy (XRT) within 28 days of the first dose of CLN-049, or craniospinal XRT within 8 weeks of the first dose of CLN-049, or history of total body irradiation (TBI).
  • a. Prior immunotherapy with checkpoint inhibitors, ≤ 42 days prior to the first dose of CLN-049.
  • b. Prior history of chimeric antigen receptor (CAR-T) cell therapy or other modified T cell therapy.
  • c. Anti-leukemic therapy except hydroxyurea for cytoreduction, and intrathecal chemotherapy > d. Short-acting hematopoietic growth factors > e. Long-acting growth factors > f. Systemic glucocorticoid therapy (except equivalent of > g. Prior treatment with a FLT3-directed bispecific molecule, or a FLT3-targeted antibody.
  • h. Currently participating/previously participated in an interventional study and received an investigational drug within 14 days (or five half-lives, whichever is longer) prior to the first dose
  • Patients with concomitant second malignancies requiring active treatment in the past 12 months, or if additional therapy is required or anticipated during study participation.
  • Patients with any active autoimmune disease or a history of known or suspected autoimmune disease, or history of a syndrome that requires systemic corticosteroids or immunosuppressive medications, except for patients with vitiligo, psoriasis (in consultation with the Sponsor), resolved childhood asthma/atopy or autoimmune thyroid disorders on stable thyroid hormone supplementation.
  • A serious uncontrolled medical disorder that would impair the ability of the patient to receive protocol therapy or whose control may be jeopardized by the complications of this therapy.
  • Additional criteria will apply

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