Gene Therapy Clinical Trials

AC220 for Children With Relapsed/Refractory ALL or AML

This is a phase I study of the investigational drug AC220 combined with cytarabine and etoposide in pediatric patients with relapsed acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML).

Stanford is currently not accepting patients for this trial.

Intervention(s):

  • drug: AC220
  • drug: Cytarabine
  • drug: Etoposide
  • drug: Methotrexate

Eligibility


Inclusion Criteria:

   - Patients must be greater than 1 month and ≤ 21 years of age at study entry.

   - Patients must have a diagnosis of relapsed/refractory AML, ALL or acute leukemia of
   ambiguous lineage and meet the following criteria:

      1. Patients with AML or leukemia with ambiguous lineage must have greater than or
      equal to 5% blasts in the bone marrow.

      2. Patients with ALL must have an M3 marrow (marrow blasts >25%).

      3. Patients with ALL must have MLL gene rearrangement or hyperdiploid >50
      chromosomes.

      4. Patients with treatment related AML (t-AML) are eligible, provided they meet all
      other eligibility criteria.

   - Karnofsky > 50% for patients >16 years of age and Lansky >50% for patients ≤16 years
   of age.

   - Patients must have fully recovered from the acute toxic effects of all prior
   chemotherapy, immunotherapy, or radiotherapy prior to entering this study.

      - Myelosuppressive chemotherapy:

         - Patients with ALL who relapse during standard maintenance therapy are
         eligible at time of relapse.

         - For patients with ALL and AML who relapse while they are receiving cytotoxic
         therapy, at least 14 days must have elapsed since the completion of
         cytotoxic therapy.

         - Cytoreduction with hydroxyurea can be initiated and continued for up to 24
         hours prior to the start of AC220.

         - Patients who have received other FLT3 inhibitors (ex. lestaurtinib,
         sorafenib) are eligible for this study.

      - Hematopoietic growth factors: At least 7 days since the completion of therapy
      with a growth factor.

      - Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy
      with a biologic agent. For agents that have known adverse events occurring beyond
      7 days after administration, this period must be extended beyond the time during
      which adverse events are known to occur. The duration of this interval must be
      discussed with the study chair.

      - XRT: 2 wks must have elapsed since local palliative XRT for CNS chloromas; No
      washout period is necessary for other chloromas; at least 3 months must have
      elapsed if prior TBI, craniospinal XRT.

      - Hematopoetic Stem Cell Transplant: At least 90 days must have elapsed since
      hematopoietic stem cell transplant (HSCT) and patients must not have active GVHD.

   - Patient must have adequate renal and hepatic functions as indicated by the following
   laboratory values:

      - Patients must have a calculated creatinine clearance or radioisotope GFR
      ≥70mL/min/1.73m2 or a normal serum creatinine based on age/gender.

      - Total bilirubin <1.5 x ULN for age or normal conjugated bilirubin.

      - Alanine transaminase (ALT) <5 × ULN (unless related to leukemic involvement).

   - Patient must have a shortening fraction of ≥ 27% by echocardiogram, OR an ejection
   fraction of ≥ 50% by radionuclide angiogram.

   - Reproductive Function

      - Female patients of childbearing potential must have a negative urine or serum
      pregnancy test confirmed within 2 weeks prior to enrollment.

      - Female patients with infants must agree not to breastfeed their infants while on
      this study.

      - Male and female patients of child-bearing potential must agree to use an
      effective method of contraception approved by the investigator during the study
      and for a minimum of 6 months after study treatment.

Exclusion Criteria:

   - Patients will be excluded if they have CNS 3 disease.

   - Patients will be excluded if they have uncontrolled or significant cardiovascular
   disease, including:

      - A myocardial infarction within 12 months.

      - Uncontrolled angina within 6 months.

      - Diagnosed or suspected congenital long QT syndrome or any history of clinically
      significant ventricular arrhythmias (such as ventricular tachycardia, ventricular
      fibrillation, or torsades de pointes [TdP]); any history of arrhythmia will be
      discussed with the Sponsor's Medical Monitor prior to patient's entry into the
      study.

      - Prolonged QTcF interval on pre-entry ECG (≥450 ms).

      - Any history of second or third degree heart block (may be eligible if the patient
      currently has a pacemaker).

      - Heart rate < 50/minute on pre-entry ECG.

      - Uncontrolled hypertension.

      - Complete left bundle branch block.

      - Any history of clinically significant ventricular arrhythmias (such as
      ventricular tachycardia, ventricular fibrillation, or TdP.

   - Patients will be excluded if they have a systemic fungal, bacterial, viral or other
   infection that is exhibiting ongoing signs/symptoms related to the infection without
   improvement despite appropriate antibiotics or other treatment. The patient needs to
   be off pressors and have negative blood cultures for 48 hours.

   - Patient is receiving or plans to receive concomitant chemotherapy, radiation therapy,
   or immunotherapy other than as specified in the protocol.

   - Any significant concurrent disease, illness, psychiatric disorder or social issue that
   would compromise patient safety or compliance, interfere with consent, study
   participation, follow up, or interpretation of study results.

   - Patients who are concurrently receiving CYP3A4 and 5 inhibitors and inducers

Ages Eligible for Study

1 Month - 21 Years

Genders Eligible for Study

All

Not currently accepting new patients for this trial

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Alyson Falwell
650-736-4281
Not Recruiting