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  • Cancer Type: Malignant Hematology
  • Study Type: Treatment
  • NCT#: NCT04278768
  • Phase: Phase I
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  • Overview

    Study Title:

    A Phase 1, Open Label Dose Escalation Trial Evaluating the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of Orally Administered CA-4948 in Patients with Acute Myelogenous Leukemia or Myelodysplastic Syndrome


    his is a multicenter, open-label, Phase 1/2a dose escalation and expansion study of orally administered CA-4948 monotherapy and in combination with azacitidine or venetoclax in adult patients with Acute Myelogenous Leukemia (AML) or high risk Myelodysplastic Syndrome (MDS).


    Primary To determine the maximum tolerated dose (MTD) and Recommended Phase 2 Dose (RP2D) for CA-4948 in patients with AML and high risk MDS based on the safety and tolerability, dose-limiting toxicities (DLTs), and PK/PD findings Secondary To characterize the pharmacokinetic

  • Treatments


    Therapy (NOS)


    CA-4948 (); GDC-0199 (Venetoclax); Venetoclax (); azacitidine (5-azacitidine)

  • Inclusion Criteria

      Inclusion Criteria:
    • Males and females 18 years of age or older
    • Life expectancy of at least 3 months
    • Eastern Cooperative Oncology Group (ECOG) Performance Status of less than or equal to 1
    • Cytomorphology based confirmed diagnosis of MDS or AML with the following characteristics. Phase 1 Dose Escalation AML (primary or secondary, including treatment-related) after failing at least 1 standard treatment (may include chemotherapy, re induction therapy or stem cell transplantation) based on the assessment of the Investigator. Higher-risk R/R MDS that are considered resistant/refractory following at least 2 to 3 cycles of hypermethylating agent (HMA) or evidence of early progression Phase 1b (Combination Therapy) Doublet Arm: CA-4948 + AZA, Patients with: IPSS-R High, hrMDS, ineligible for intensive chemotherapy Doublet Arm: CA-4948 + Venetoclax
    • Patients with R/R AML
    • FLT3-ITD mutations who have been previously treated with a FLT3 inhibitor
    • R/R AML spliceosome mutations of SF3B1 or U2AF1
    • R/R hrMDS with spliceosome mutations of SF3B1 or U2AF1 and have had > Patients with
    • R/R AML with FLT-3 mutations who have been previously treated with a FLT3 inhibitor
    • R/R hrMDS with spliceosome mutations of SF3B1 or U2AF1 AND
    • Have had > Acceptable organ function at screening
    • Ability to swallow and retain oral medications
    • Negative serum pregnancy test in women of childbearing potential
    • Women of childbearing potential and men who partner with a woman of childbearing potential must agree to use highly effective contraceptive methods for the duration of the study and for 90 days after the last dose of CA-4948
    • Willing and able to provide written informed consent and comply with the requirements of the trial
    • Able to undergo serial bone marrow sampling and peripheral blood sampling Other criteria may apply
  • Exclusion Criteria

      Exclusion Criteria:
    • Diagnosed with acute promyelocytic leukemia (APL, M3)
    • Has known active central nervous system (CNS) leukemia
    • Allogeneic hematopoietic stem cell transplant (Allo-HSCT) within 60 days of the first dose of CA-4948, or clinically significant graft-versus-host disease (GVHD) requiring ongoing up titration of immunosuppressive medications prior to start of CA-4948
    • Chronic myeloid leukemia (CML)
    • Any prior systemic anti-cancer treatment such as chemotherapy, immunomodulatory drug therapy, etc., received within 3 weeks (or 5 half-lives) whichever is shorter, or radiotherapy received 2 weeks prior to the start of CA-4948.Note: Localized radiation or surgical resection of skin cancers is allowed.
    • Use of any investigational agent within 3 weeks (or 5 half-lives), whichever is shorter, prior to start of CA-4948
    • Presence of an acute or chronic toxicity resulting from prior anti-cancer therapy, with the exception of alopecia that has not resolved to Grade ≤1 as determined by the NCI-CTAE v4.03 within 7 days prior to start of CA-4948 unless approved by the Medical Monitor.
    • Known allergy or hypersensitivity to any component of the formulation of CA-4948
    • Major surgery, other than diagnostic surgery, less than 28 days from the start of CA-4948; minor surgery less than 14 days from the start of CA-4948
    • Patients with active advanced malignant solid tumors
    • Viral Infections:
    • Known to be human immunodeficiency virus (HIV) positive or have an acquired immunodeficiency syndrome-related illness
    • Hepatitis B virus (HBV) DNA positive or Hepatitis C virus (HCV) infection > Concomitant illnesses that would preclude safe participation in the study, identified within approximately 28 days of C1D1, including:
    • Uncontrolled or severe cardiovascular disease
    • Gastrointestinal disease or disorder that could interfere with the swallowing, oral absorption, or tolerance of CA-4948
    • Any other severe, acute, or chronic medical, psychiatric or social condition, or laboratory abnormality that may increase the risk of trial participation or CA-4948 administration
    • Systemic fungal, bacterial, viral or other infection that is not controlled
    • Pregnant or lactating
    • Other criteria may apply

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