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

Condition(s) targeted: Leukemia; Myelodysplastic Syndromes

Intervention: liposomal daunorubicin citrate (Drug); semaxanib (Drug)

Phase: Phase 1/Phase 2

Status: Completed

Sponsored by: M.D. Anderson Cancer Center

Official(s) and/or principal investigator(s):
Francis J. Giles, MD, Study Chair, Affiliation: M.D. Anderson Cancer Center

RATIONALE: 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.

PURPOSE: 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.

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 design: Treatment

Detailed description: OBJECTIVES: 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

DISEASE CHARACTERISTICS: Diagnosis of acute myeloid leukemia, refractory anemia with excess blasts (RAEB), RAEB in transformation, or chronic myelomonocytic leukemia in transformation Not in complete remission 21-50 days after beginning course one of initial induction chemotherapy No more than 1 course of prior chemotherapy containing the following: Cytarabine at a dose of at least 1 g/m2 daily for 4 days AND Topotecan OR an anthracycline at standard doses: Daunorubicin no greater than 65 mg/m2 daily for 3 days OR Idarubicin 12 mg/m2 daily for 3 days Patients beginning study on days 21-42 of course one must have persistent blasts in bone marrow or blood with no evidence of improvement Patients beginning study on days 42-50 may or may not have persistent blasts but must have thrombocytopenia or neutropenia that is not improving No prior CNS hemorrhage

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Zubrod 0 or 1 Life expectancy: Not specified Hematopoietic: See Disease Characteristics Hepatic: Bilirubin no greater than 1. 5 mg/dL SGOT or SGPT no greater than 2. 5 times upper limit of normal Renal: Creatinine no greater than 1. 5 mg/dL Cardiovascular: No uncompensated coronary artery disease No myocardial infarction or severe/unstable angina in the past 6 months LVEF at least 40% by MUGA or echocardiography No severe peripheral vascular disease No deep venous or arterial thrombosis within the past 3 months Pulmonary: No pulmonary embolism with the past 3 months Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No active infection No psychosis or mental disability that would preclude study No known allergy to Cremophor or Cremophor based drug products, corticosteroids, H1 blockers, H2 blockers, or paclitaxel No diabetes mellitus No acute or chronic medical or psychiatric condition, or laboratory abnormality, that would increase risks associated with study

PRIOR CONCURRENT THERAPY: Biologic therapy: At least 2 weeks since prior recombinant growth factors No concurrent biologic anticancer therapy No concurrent colony stimulating factors No prior angiogenesis inhibitor therapy (including metalloproteinase inhibitors, thalidomide, antiVEGF/Flk-1 monoclonal antibody therapy, or other investigational drugs which act on this pathway) Chemotherapy: See Disease Characteristics At least 2 weeks since prior chemotherapy and recovered No other concurrent chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior stereotactic CNS radiotherapy No concurrent systemic radiotherapy Surgery: At least 1 week since prior minor surgery At least 2 weeks since prior major surgery No concurrent surgery Other: No prior organ transplant At least 2 weeks since prior antibiotics At least 2 weeks since prior investigational agents No other concurrent investigational agents No concurrent antibiotics for active infection

University of Texas - MD Anderson Cancer Center, Houston, Texas 77030, United States

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: March 2000
Last updated: May 23, 2008