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A Phase I Study of DT388GMCSF Fusion Protein in Acute Myelogenous Leukemia (AML) and Chronic Myelomonocytic Leukemia (CMML)

Phase 1
18 Years
Not Enrolling
Acute Myelogenous Leukemia, Chronic Myelomonocytic Leukemia

Thank you

Trial Information

A Phase I Study of DT388GMCSF Fusion Protein in Acute Myelogenous Leukemia (AML) and Chronic Myelomonocytic Leukemia (CMML)

The majority of malignant myeloid progenitor cells express receptors for GM-CSF. The fusion
of GM-CSF with diphtheria toxin allows a targeting of cells with GM-CSF receptors for
effects of the toxin while sparing GM-CSF receptor-lacking multipotent stem cells. The great
majority of AML cells express GM-CSF receptors and DT388GMCSF has shown selective killing
of AML and CMML progenitors in vitro while sparing normal progenitor cells. When
administered as a single bolus to rodents, adequate blood DT388GMCSF biological activity
was found to kill several logs of leukemic cells. A phase I clinical trial of DT388GMCSF
given as a daily bolus i.v. infusion for up to 5 consecutive days was completed in 38
patients. The study defined liver toxicity as the DLT. The liver toxicity was observed only
in patients > 50 years and receiving steroids. Responses were seen in four patients
consisting of one complete remission and 3 partial remission of short duration. Peak drug
levels were inversely proportional to pre-treatment DT388GMCSF antibody levels.

Because of the observed significant preclinical activity in AML and CMML, clinical activity
in chemorefractory patients with AML, the association of toxicities with steroid exposure,
and association of the drug level with antibody titer that could be decreased with
DT388GMCSF exposure, the current follow up phase I trial is designed based on a new
administration and is a dose - finding trial also aimed to better determine and control
side effects, improve drug pharmacokinetics and provide initial insight into antileukemic
activity of this novel agent, delivered at a prolonged intermittent schedule.

Inclusion Criteria:

- Patients with refractory or relapsed AML ( marrow blasts > 20% ), must have failed
induction therapy or have relapsed after CR duration < 6 months following induction
therapy, untreated or refractory to salvage chemotherapy. Relapsed AML patients with
CR duration > 6 months or previously untreated patients refusing chemotherapy and not
considered for treatments of higher priority are also eligible.

- Patients with chronic myelomonocytic leukemia (CMML) who failed at least one course
of chemo- or biological therapy( including trial of erythropoietin), or patients with
relapsed CMML. Previously untreated CMML patients with HB < or = 12 g / dL, not
eligible for protocols of higher priority or not wishing to receive chemotherapy.

- Patients must have an ECOG performance status of < 2.

- Patients must have WBC count < 10,000/mL prior to initiating the treatment. The WBC
count must be stabilized below this level for at least three days by leukopheresis or
hydroxyurea. Hydroxyurea must be discontinued one day prior to initiation of
DT388GMCSF treatment.

- Patients must have creatinine < 1.6 times ULN: bilirubin <1.6 times ULN; SGPT < 2.6
x ULN; albumin > 3 gm/dl; adequate cardiac function (EF >44%), oxygen saturation >
92% without exogenous oxygen administered.

- Patients must be willing to be treated at M D Anderson Cancer Center.

- Women of childbearing potential and men must agree to practice contraception using
approved methods.

- No chemotherapy except Hydroxyurea 2 weeks prior to entering the study and recovered
from previous toxicity.

- Patients must be > 17 years old.

Exclusion Criteria:

- Patients with serious concurrent medical problems. Patients with proven bacterial
infections are not eligible until the resolution of the infection (patient afebrile
who completed antibacterial therapy, not on steroids). Patients with active fungal
infections are eligible only if evidence of response to antifungal medications is
documented and fever does not exceed 38C for at least 2 days.

- Inability to give informed consent because of psychiatric problems or other serious
medical problems.

- Pregnant or nursing women.

- Patients with documented CNS leukemia or leukemia with CNS symptoms.

- Patients who have had a myocardial infarction within the past six months.

- Patients with severe penicillin allergy (anaphylaxis).

- Not fully recovered from toxic effects of prior chemotherapy or radiation therapy.

- Patients who are on corticosteroid treatment for any medical condition.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Principal Investigator

Miloslav Beran, MD, PhD, DVM

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

December 2003

Completion Date:

December 2004

Related Keywords:

  • Acute Myelogenous Leukemia
  • Chronic Myelomonocytic Leukemia
  • AML
  • CMML
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myelomonocytic, Chronic
  • Leukemia, Myelomonocytic, Acute



The University of Texas M.D. Anderson Cancer Center Houston, Texas