Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

SB-715992 in Treating Patients With Acute Leukemia, Chronic Myelogenous Leukemia, or Advanced Myelodysplastic Syndromes

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Closed 18 and over NCI CASE-CWRU-3904 NCI-6777, 6777, NCT00098826, CWRU-070418, CASE-3904

Objectives

Primary

1. Determine the maximum tolerated dose of SB-715992 in patients with acute leukemia, chronic myelogenous leukemia, or advanced myelodysplastic syndromes.
2. Determine pharmacokinetics of this drug in these patients.
3. Determine the treatment-related and dose-limiting toxic effects of this drug in these patients.
4. Determine the antileukemia activity of this drug, in terms of clearing of circulating peripheral blasts, attainment of aplastic bone marrow, and achievement of complete or partial remission, in these patients.
5. Correlate treatment-related toxic effects with pharmacokinetics of this drug in these patients.

Secondary

1. Correlate, if possible, gene expression with response in patients treated with this drug.

Entry Criteria

Disease Characteristics:

• Diagnosis of 1 of the following:
  • Acute myeloid leukemia
    • Refractory to primary standard induction therapy
  • Acute lymphoblastic leukemia
    • Refractory to primary standard induction therapy
  • Acute leukemia
    • Relapsed or refractory disease
  • Chronic myelogenous leukemia in blast crisis at diagnosis OR after failing aggressive induction chemotherapy AND refractory to imatinib mesylate
  • Acute leukemia secondary to a preexisting hematologic condition or prior chemotherapy regimen at diagnosis OR after failing aggressive induction chemotherapy
  • Advanced myelodysplastic syndromes
    • Refractory anemia with excess blasts (RAEB) or RAEB in transformation provided patient is neutropenic or transfusion dependent
  • De novo acute myeloid leukemia not eligible for aggressive standard induction chemotherapy due to advanced age or serious comorbid medical or psychiatric condition
    • Patients > 60 years of age with unfavorable cytogenetics are eligible



• No suspected or known CNS leukemia

Prior/Concurrent Therapy:

Biologic therapy

• At least 3 months since prior autologous stem cell transplantation and recovered
• At least 2 weeks since prior pegfilgrastim
• At least 2 weeks since prior gemtuzumab or ozogamicin
• At least 2 weeks since prior biologic therapy
• At least 5 days since prior filgrastim (G-CSF) or sargramostim (GM-CSF)
• No prior allogeneic stem cell transplantation
• No concurrent biologic therapy

Chemotherapy

• See Disease Characteristics
• At least 24 hours since prior hydroxyurea
• At least 2 weeks since prior cytotoxic chemotherapy
• No other concurrent cytotoxic chemotherapy

Endocrine therapy

• At least 24 hours since prior corticosteroids
• No concurrent hormonal therapy except hormone replacement therapy

Radiotherapy

• No concurrent radiotherapy

Surgery

• Not specified

Other

• At least 24 hours since prior imatinib mesylate
• At least 4 weeks since prior investigational agents
• More than 14 days since prior and no concurrent moderate or significant CYP3A4 inhibitors or inducers as follows:
  • Clarithromycin
  • Erythromycin
  • Troleandomycin
  • Itraconazole
  • Ketoconazole
  • Fluconazole (> 200 mg/day)
  • Voriconazole
  • Nefazodone
  • Fluvoxamine
  • Verapamil
  • Diltiazem
  • Grapefruit juice
  • Bitter orange
  • Phenytoin
  • Carbamazepine
  • Phenobarbital
  • Oxcarbazepine
  • Rifampin
  • Rifabutin
  • Rifapentine
  • Hypericum perforatum (St. John's wort)
  • Modafinil
• At least 6 months since prior and no concurrent amiodarone
• No other concurrent anticancer therapy
• No other investigational medications during and for 14 days after study treatment

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

  OR

• Karnofsky 50-100%

Life expectancy

• At least 4 weeks

Hematopoietic

• See Disease Characteristics

Hepatic

• Bilirubin ≤ 1.5 mg/dL
• AST and ALT < 3 times upper limit of normal (ULN)

Renal

• Creatinine ≤ 1.5 times ULN

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Pulmonary

• No poorly controlled pulmonary disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• No prexisting neuropathy ≥ grade 2
• No history of allergic reaction attributed to compounds of similar chemical or biologic composition to SB-715992
• No other uncontrolled illness
• No active or poorly controlled infection
• No psychiatric illness or social situation that would preclude study compliance

Expected Enrollment

Approximately 15-30 patients will be accrued for this study within 7.5-15 months.

Outcomes

Toxicity by physical exam every 3 weeks and laboratory tests weekly
Disease response by bone marrow biopsy once blood count has recovered or at day 35 and then every 3 weeks

Outline

This is a dose-escalation, multicenter study.

• Induction chemotherapy: Patients receive SB-715992 IV over 1 hour on days 1-3. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.



• Consolidation chemotherapy: Patients achieving complete response (CR), partial response (PR), or stable disease (SD) after induction chemotherapy receive up to 4 additional courses of SB-715992 beyond CR, PR, or SD.

Cohorts of 3-6 patients receive SB-715992 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 9 patients are treated at the MTD.

Patients are followed for 6 weeks.

Trial Contact Information

Trial Lead Organizations

Case Comprehensive Cancer Center

Brenda Cooper, MD, Principal investigator		Ph: 216-844-3213 Email: bxc12@po.cwru.edu

Registry Information
Official Title		Phase I and Pharmacodynamic Study of SB-715992 in Acute Leukemias
Trial Start Date		2004-12-07
Trial Completion Date		2006-07-30 (estimated)
Registered in ClinicalTrials.gov		NCT00098826
Date Submitted to PDQ		2004-10-07
Information Last Verified		2008-05-24
NCI Grant/Contract Number		CA62502, CA43703