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

NCT00098826 | Completed Phase 1

• 4 other identifiers: NCI-2012-03127CASE 3904U01CA062502U01CA062505
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Phase I trial to study the effectiveness of SB-715992 in treating patients who have acute leukemia, chronic myelogenous leukemia, or advanced myelodysplastic syndromes. Drugs used in chemotherapy, such as SB-715992, work in different ways to stop cancer cells from dividing so they stop growing or die

Conditions

Acute Undifferentiated Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (7)

• Maximum tolerated dose (MTD) of ispinesib, based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0

  Up to day 28

• Pharmacokinetics of ispinesib in terms of total systemic clearance, peak concentration, area under the curve (AUC), and half-lives

  Summarized with histograms, medians, quartiles and ranges. Scatterplots and correlation coefficients will be used to evaluate the association between the pharmacokinetic (PK) variables and the ispinesib dose, as well the changes in the peripheral blood mononuclear cell (PBMC) values.

  Up to 96 hours post-infusion

• Treatment-related and dose-limiting toxicities of ispinesib, based on the NCI CTCAE v3.0

  Up to 2 years

• Clearing of circulating peripheral blasts

  By 35 days from start of most recent course of chemotherapy

• Attainment of aplastic bone marrow

  Scatterplots, means, standard deviations, and confidence intervals will be constructed to compare responders and non-responders.

  By 35 days from start of most recent course of chemotherapy

• Achievement of complete or partial remission

  Scatterplots, means, standard deviations, and confidence intervals will be constructed to compare responders and non-responders.

  By 35 days from start of most recent course of chemotherapy

• Correlation between treatment-related toxicities with pharmacokinetic studies

  Scatterplots, means, standard deviations, and confidence intervals will be constructed to compare responders and non-responders.

  By 35 days from start of most recent course of chemotherapy

Study Arms (1)

Treatment (ispinesib)

EXPERIMENTAL

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 CR, PR, or 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 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.

Drug: ispinesib; Other: laboratory biomarker analysis; Other: pharmacological study

Interventions

ispinesib DRUG

Given IV

Also known as: CK0238273, SB-715992

Treatment (ispinesib)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (ispinesib)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (ispinesib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have acute myelogenous or acute lymphoblastic leukemia refractory to primary standard induction therapy; relapsed/refractory acute leukemia; chronic myelogenous leukemia in blast crisis are eligible at diagnosis or after failing aggressive induction chemotherapy (providing they are refractory to imatinib); acute leukemia secondary to preexisting hematologic condition or prior chemotherapy are eligible at diagnosis or after failing aggressive induction chemotherapy, advanced myelodysplastic syndrome (RAEB or RAEB-2 providing they are neutropenic or transfusion dependent); patients with de-novo acute leukemia who are not eligible for aggressive standard induction chemotherapy due to advanced age or serious comorbid medical or psychiatric conditions, patients above age 60 with de-novo AML and unfavorable cytogenetics
• At least 2 weeks must have elapsed between completion of most recent cytotoxic chemotherapy, or biologic therapy except for hydroxyurea or corticosteroids or Imatinib (24 hours); patients who have previously received an autologous stem cell transplant are allowed providing a minimum of 3 months has elapsed from transplant (T0) and patient has recovered from transplant associated toxicities; patients who have had prior allogeneic stem cell transplant are not eligible; a minimum of five days must have elapsed since administration of granulocyte or granulocyte-macrophage colony-stimulating factor and a minimum of 2 weeks if Neulasta; minimum of 2 weeks since administration of gemtuzumab, ozogamicin (Mylotarg), minimum of 4 weeks for prior investigational agents
• ECOG performance status =\< 2 (Karnofsky \>= 50%)
• Life expectancy of at least 4 weeks
• Direct serum bilirubin =\< 1.5 mg/dl
• AST(SGOT)/ALT(SGPT) \< 3 X institutional upper limit of normal
• Creatinine =\< 1.5 X institutional upper limit of normal
• The effects of SB-715992 on the developing human fetus are unknown; for this reason and because mitotic inhibitors are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Ability to understand and the willingness to sign a written informed consent document

You may not qualify if:

• Patients may not have received any other investigational agents within 28 days of study entry
• Patients may not receive any other anti-cancer therapy (cytotoxic, biologic, radiation, or hormonal other than for replacement) while on this study
• Prohibited medications: SB-715992 is a moderate to significant in vitro inhibitor of CYP3A4; the following lists of medications/substances are moderate to significant inhibitors/inducers of CYP3A4 that, if administered concomitantly with SB-715992, may alter study drug exposure; the use of these medications/substances within 14 days (\>= 6 months for amiodarone) prior to the administration of the first dose of SB-715992 through discontinuation from the study is prohibited
• Inhibitors of CYP3A4:
• Antibiotics: clarithromycin, erythromycin, troleandomycin
• Antifungals: itraconazole, ketoconazole, fluconazole (doses \> 200 mg/day), voriconazole
• Antidepressants: nefazodone, fluvoxamine
• Calcium channel blockers: verapamil, diltiazem
• Miscellaneous: amiodarone\*, grapefruit juice, bitter orange; \*use of amiodarone within 6 months prior to the administration of the first dose of SB-715992 is prohibited
• Inducers of CYP3A4:
• Anticonvulsants: phenytoin, carbamazepine, phenobarbital, oxcarbazepine
• Antibiotics: rifampin, rifabutin, rifapentine
• Miscellaneous: St. John's wort, modafinil
• Patients with suspected or proven CNS leukemia (diagnostic lumbar puncture not required before enrollment)
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to SB-715992

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

MeSH Terms

Conditions

Leukemia, Biphenotypic, Acute; Leukemia, Megakaryoblastic, Acute; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Congenital Abnormalities; Leukemia, Myelomonocytic, Acute; Leukemia, Promyelocytic, Acute; Leukemia, Erythroblastic, Acute; Blast Crisis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Anemia, Refractory, with Excess of Blasts

Interventions

ispinesib; CK0238273

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Myeloproliferative Disorders; Bone Marrow Diseases; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Anemia, Refractory; Anemia; Myelodysplastic Syndromes

Study Officials

• Brenda Cooper

  Case Western Reserve University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2004
• First Posted: December 9, 2004
• Study Start: December 1, 2004
• Primary Completion: May 1, 2008
• Last Updated: January 11, 2013

Record last verified: 2013-01

Locations

US (1)