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Acute Undifferentiated LeukemiaPhase 1NCT00098826

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

A Phase 1 study testing ispinesib, laboratory biomarker analysis and pharmacological study in people with Acute Undifferentiated Leukemia and Adult Acute Megakaryoblastic Leukemia (M7), run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
ispinesib, laboratory biomarker analysis and pharmacological study
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
1 siteUnited States
Study dates
Dec 2004to May 2008
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active or poorly controlled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, poorly controlled pulmonary disease or psychiatric illness/social situations that would limit compliance with study requirements
  • Patients with pre-existing neuropathy of grade 2 or higher are not eligible to participate
  • Pregnant women are excluded from this study because SB-715992 is a mitotic inhibitor with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with SB-715992, breastfeeding should be discontinued if the mother is treated with SB-715992
  • Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy; therefore, HIV-positive patients are excluded from this study

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Case Western Reserve University

    Cleveland, Ohio, 44106

Other trials in United States

About this study

Official title: Phase I and Pharmacodynamic Study of SB-715992 in Acute Leukemias

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

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximum tolerated dose (MTD) of SB-715992 given as a daily x 3 infusion in patients with acute leukemia.

II. To obtain pharmacokinetic studies of SB-715992 given on a 3 consecutive day schedule every 3 weeks.

III. To describe treatment-related and dose-limiting toxicities of SB-715992 in patients with acute leukemia.

IV. To describe the anti-leukemia activity of SB-715992. V. To correlate treatment-related toxicities with pharmacokinetic studies of SB-715992.

SECONDARY OBJECTIVES:

  1. To validate KSP as the major target of SB-715992 by determining the impact of drug treatment on cytoskeletal morphology in peripheral blood mononuclear cells and circulating leukemic blasts.

II. To determine the expression of tubulin isoforms and KSP in leukemic blasts and explore possible relationships between gene expression and response to SB-715992.

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.

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

Being tested
ispinesib, laboratory biomarker analysis, pharmacological study
Medical subject headings
Leukemia, Biphenotypic, Acute, Leukemia, Megakaryoblastic, Acute, Leukemia, Monocytic, Acute, Leukemia, Myeloid, Acute, Congenital Abnormalities, Leukemia, Myelomonocytic, Acute, Leukemia, Promyelocytic, Acute, Leukemia, Erythroblastic, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ispinesibDrug

    Also called CK0238273, SB-715992

    Given IV

  • laboratory biomarker analysisOther

    Correlative studies

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

Study groups in NCT00098826
Study groupRoleWhat they receive
Treatment (ispinesib)ExperimentalInduction 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.
Receives: Drug: ispinesib; Other: laboratory biomarker analysis; Other: pharmacological study

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: Up to day 28

  2. 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.

    Measured: Up to 96 hours post-infusion

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

    Measured: Up to 2 years

  4. Clearing of circulating peripheral blasts

    Measured: By 35 days from start of most recent course of chemotherapy

  5. Attainment of aplastic bone marrow

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

    Measured: By 35 days from start of most recent course of chemotherapy

  6. Achievement of complete or partial remission

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

    Measured: By 35 days from start of most recent course of chemotherapy

  7. Correlation between treatment-related toxicities with pharmacokinetic studies

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

    Measured: By 35 days from start of most recent course of chemotherapy

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Dec 2004 (estimated)
  2. Study startDec 2004
  3. Primary completionMay 2008

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00098826
Sponsor's protocol ID
NCI-2012-03127
Other IDs
CASE 3904, U01CA062502, U01CA062505
Status last verified
Jan 2013
First submitted
8 Dec 2004
Last updated
11 Jan 2013
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ispinesib, laboratory biomarker analysis and pharmacological study in people with Acute Undifferentiated Leukemia and Adult Acute Megakaryoblastic Leukemia (M7), run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum tolerated dose (MTD) of ispinesib, based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0 (time frame: Up to day 28). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jan 2013.

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