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Liposomal Daunorubicin and SU5416 in Treating Patients With Hematologic Cancer That Has Not Responded to Initial Therapy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00005942
Recruitment Status : Completed
First Posted : May 26, 2004
Last Update Posted : January 23, 2013
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
Phase I/II trial to study the effectiveness of liposomal daunorubicin and SU5416 in treating patients who have hematologic cancer that has not responded to initial therapy. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. SU5416 may stop the growth of hematologic cancer by stopping blood flow to the cancer

Condition or disease Intervention/treatment Phase
Chronic Myelomonocytic Leukemia Previously Treated Myelodysplastic Syndromes Recurrent Adult Acute Myeloid Leukemia Refractory Anemia With Excess Blasts Refractory Anemia With Excess Blasts in Transformation Drug: liposomal daunorubicin citrate Drug: semaxanib Other: laboratory biomarker analysis Phase 1 Phase 2

Detailed Description:


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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 37 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : March 2000
Actual Primary Completion Date : December 2000

Arm Intervention/treatment
Experimental: Treatment (liposomal danorubicin citrate, semaxanib)
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.
Drug: liposomal daunorubicin citrate
Given IV
Other Names:
  • daunorubicin liposomal
  • DaunoXome
  • liposomal daunorubicin

Drug: semaxanib
Given IV
Other Names:
  • semoxind
  • SU5416
  • Sugen 5416

Other: laboratory biomarker analysis
Correlative studies

Primary Outcome Measures :
  1. MTD of semaxanib defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicities [ Time Frame: 2 months ]
    Graded according to NCI CTC version 2.0.

  2. Achievement of CR, defined as normalization of the peripheral blood and bone marrow with 5% or less blasts, normo-or hypercellular marrow, a granulocyte count of 1x 10^9 L or above, and a platelet count of 100 x 10^9 L or above [ Time Frame: Up to 1 year ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 consent
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00005942

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United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
National Cancer Institute (NCI)
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Principal Investigator: Francis Giles M.D. Anderson Cancer Center
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Responsible Party: National Cancer Institute (NCI) Identifier: NCT00005942    
Other Study ID Numbers: NCI-2012-02329
CDR0000067822 ( Registry Identifier: PDQ (Physician Data Query) )
First Posted: May 26, 2004    Key Record Dates
Last Update Posted: January 23, 2013
Last Verified: January 2013
Additional relevant MeSH terms:
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Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Myelodysplastic Syndromes
Anemia, Refractory
Anemia, Refractory, with Excess of Blasts
Neoplasms by Histologic Type
Leukemia, Myeloid
Hematologic Diseases
Bone Marrow Diseases
Myelodysplastic-Myeloproliferative Diseases
Molecular Mechanisms of Pharmacological Action
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors