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Phase II Trial of Liposomal Daunorubicin (Daunoxome) and SU5416 (NSC 696819) in Patients With AML, RAEB, RAEB-T or CMML in Transformation Refractory to One Course of Induction Chemotherapy

Phase 1/Phase 2
18 Years
Not Enrolling
Chronic Myelomonocytic Leukemia, Previously Treated Myelodysplastic Syndromes, Recurrent Adult Acute Myeloid Leukemia, Refractory Anemia With Excess Blasts, Refractory Anemia With Excess Blasts in Transformation

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Trial Information

Phase II Trial of Liposomal Daunorubicin (Daunoxome) and SU5416 (NSC 696819) in Patients With AML, RAEB, RAEB-T or CMML in Transformation Refractory to One Course of Induction Chemotherapy


I. Determine the maximum tolerated dose of SU5416 when administered with daunorubicin
liposomal in patients with acute myeloid leukemia, refractory anemia with excess blasts
(RAEB), RAEB in transformation, or chronic myelomonocytic leukemia not in complete remission
21-50 days after one course of induction chemotherapy.

II. Determine the efficacy of this regimen in these patients. III. Determine the
qualitative and quantitative toxicities of this regimen in these patients.

OUTLINE: This is a dose escalation study of SU5416.

Patients receive daunorubicin liposomal IV over 6 hours on days 1-3 and SU5416 IV twice a
week for 2 months. The second course is administered for 1 month, then treatment continues
every 4-6 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of SU5416 until the maximum tolerated dose
(MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients
experience dose limiting toxicities.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 12-37 patients will be accrued for this study within 1 year.

Inclusion Criteria:

- Adult patients with AML, RAEB, RAEB-T or CMML-T that are not in CR 21-50 days after
beginning course one of initial induction chemotherapy; patients may not have
received more than 1 prior course of chemotherapy prior to study entry; this must
contain Ara-C at a dose of at least 1 g/m^2 daily x 4 days and either topotecan or an
anthracycline at standard doses (i.e., daunorubicin =< 65 mg/m^2 daily x 3 days, or
idarubicin 12 mg/m^2 daily x 3 days); patients beginning liposomal Daunorubicin on
days 21 to 42 of course one must have persistent blasts in bone marrow or blood
without evidence of improvement; patients beginning liposomal Daunorubicin on days 42
to 50 may or may not have persistent blasts but must have thrombocytopenia or
neutropenia that is not improving

- Patients must have recovered from the toxic effects of prior therapy with a minimum
interval of 14 days from prior therapy and must not have received recombinant growth
factors during this period

- Patients of any racial and ethnic group

- Zubrod performance status =< 1

- Total bilirubin value =< 1.5 mg/dL

- Serum creatinine value =< 1.5 mg/dL

- Serum sGOT or sGPT =< 2.5 times the upper lim it of normal

- Patients must agree to practice approved methods of birth control (if applicable)

- Patients must provide written informed consent

- Patients from any gender or ethnic background may be included; over the last 5 years,
356 patients with relapsed or refractory acute leukemias that would meet the
eligibility criteria for this study have been treated at M.D. Anderson Cancer Center,
for an annual average of 70 patients; the race (as defined by the patient on
admission questionnaire) and sex distribution for these patients

Exclusion Criteria:

- Concurrent cancer chemotherapy, systemic radiotherapy or surgery

- Patients should not have any evidence of an active infectious process or be receiving
antibiotic therapy for an infectious process, either documented or presumed, at the
time of study entry or for 2 weeks prior to study entry

- Because of the potential effects of SU5416 on the embryo, women with the potential to
become pregnant, unless utilizing birth control, or who are pregnant are excluded
from the study; a negative pregnancy test must be documented during the screening
period for women of childbearing potential; breast-feeding women are excluded from
this trial because of the potential toxicity to the child; men of childfathering
potential should use a medically acceptable form of birth control while on study

- Overt psychosis or mental disability or otherwise incompetent to give informed

- Receipt of any of the following prior to SU5416 administration:

- major surgery within 2 weeks; minor surgery within 1 week

- any previous angiogenesis inhibitor therapy (including metalloproteinase
inhibitors, thalidomide, anti-VEGF/Flk-1 monoclonal antibody therapy or other
investigational drugs which act directly on the VEGF/Flk-1 signaling pathway)

- organ transplant at any time

- Known allergy to Cremophor beta or Cremophor beta-based drug products,
corticosteroids; H1 blockers, H2 blockers or paclitaxel; patients with uncompensated
coronary artery disease on electrocardiogram or physical examination, or with a
history of myocardial infarction or severe/unstable angina in the past 6 months are
not eligible; patients with a cardiac left ventricular ejection fractions (LVEF) by
MUGA or echocardiography of < 40% are not eligible

- Patients with diabetes mellitus and others with severe peripheral vascular disease
and patients who have had a deep venous or arterial thrombosis (including pulmonary
embolism) within 3 months of entry are not eligible

- Prior CNS hemorrhage or prior sterotactic CNS radiation

- Any acute or chronic medical or psychiatric condition, or a laboratory abnormality
that may increase the risks associated with study participation/study drug
administration or may interfere with the interpretation of study results

Type of Study:


Study Design:

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

Outcome Measure:

MTD of semaxanib defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicities

Outcome Description:

Graded according to NCI CTC version 2.0.

Outcome Time Frame:

2 months

Safety Issue:


Principal Investigator

Francis Giles

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

March 2000

Completion Date:

Related Keywords:

  • Chronic Myelomonocytic Leukemia
  • Previously Treated Myelodysplastic Syndromes
  • Recurrent Adult Acute Myeloid Leukemia
  • Refractory Anemia With Excess Blasts
  • Refractory Anemia With Excess Blasts in Transformation
  • Anemia
  • Anemia, Refractory
  • Anemia, Refractory, with Excess of Blasts
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myelomonocytic, Chronic
  • Myelodysplastic Syndromes
  • Preleukemia
  • Leukemia, Myelomonocytic, Acute
  • Anemia, Aplastic



M D Anderson Cancer Center Houston, Texas  77030