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Accelerated Phase Chronic Myelogenous LeukemiaPhase 1NCT00316953

Dasatinib in Treating Young Patients With Recurrent or Refractory Solid Tumors or Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia or Chronic Myelogenous Leukemia That Did Not Respond to Imatinib Mesylate

A Phase 1 study testing dasatinib, pharmacological study and laboratory biomarker analysis in people with Accelerated Phase Chronic Myelogenous Leukemia and Blastic Phase Chronic Myelogenous Leukemia, 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

This phase I trial is studying the side effects and best dose of dasatinib in treating young patients with recurrent or refractory solid tumors or Philadelphia chromosome-positive acute lymphoblastic leukemia or chronic myelogenous leukemia that did not respond to imatinib mesylate. Read more about this study

Who is it for?
Ages 1 year to 21 years
What is being tested?
dasatinib, pharmacological study and laboratory biomarker analysis
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
48 participants
Where
1 siteUnited States
Study dates
Mar 2006to Sep 2009
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 1 year to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Histologically confirmed diagnosis of 1 of the following:
  • Malignant extracranial solid tumor
  • Recurrent or refractory disease
  • Known bone marrow metastases* allowed
  • Imatinib mesylate-resistant Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), defined as M3 bone marrow in a patient who previously received imatinib mesylate-containing treatment regimen
  • Imatinib mesylate-resistant Ph+ chronic myelogenous leukemia (CML), as defined by any of the following:
Show all 84Show fewer
  • Increasing WBC or platelet count while on imatinib mesylate therapy
  • Lack of any cytogenetic response after an adequate duration of imatinib mesylate therapy, as defined by 1 of the following:
  • Failed to achieve a complete hematologic response after completion of 3 months of imatinib mesylate treatment
  • Failed to achieve a partial or complete cytogenetic response (i.e., ≤ 35% Ph+ cells) after 6 months of imatinib mesylate treatment
  • Appearance of accelerated or blastic feature while on imatinib mesylate therapy
  • Reappearance of Ph+ clones after an initial complete cytogenetic response to imatinib mesylate
  • More than 30% increase in Ph+ cells in peripheral blood or bone marrow cytogenetics while on imatinib mesylate therapy
  • Imatinib mesylate intolerance, as defined by development of adverse effects requiring discontinuation of imatinib mesylate therapy
  • Measurable disease (for patients with CML or ALL)
  • Determined by hematologic, cytogenetic, and molecular studies for CML
  • Determined by bone marrow blast percentage for ALL
  • Measurable or evaluable disease (for patients with solid tumors)
  • No known curative therapy or survival-prolonging therapy with an acceptable quality of life
  • No CNS solid tumors
  • CNS-positive leukemia allowed
  • Karnofsky performance status (PS) ≥ 50% (for patients > 10 years of age)
  • Lansky PS ≥ 50% (for patients ≤ 10 years of age)
  • No evidence of graft-vs-host disease
  • Solid tumors:
  • Absolute neutrophil count ≥ 1,000/mm^3 (750/mm^3 if bone marrow infiltration)
  • Platelet count ≥ 100,000/mm^3 (transfusion independent) (50,000/mm^3 if bone marrow infiltration)
  • Hemoglobin ≥ 8.0 g/dL (red blood cell [RBC] transfusions allowed)
  • ALL/CML:
  • Platelet count ≥ 20,000/mm^3 (platelet transfusions allowed)
  • Hemoglobin ≥ 8.0 g/dL (RBC transfusions allowed)
  • Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR creatinine based on age, as follows:
  • No greater than 0.6 mg/dL (1-23 months of age)
  • No greater than 0.8 mg/dL (2- 5 years of age)
  • No greater than 1.0 mg/dL (6-9 years of age)
  • No greater than 1.2 mg/dL (10-12 years of age)
  • No greater than 1.4 mg/dL (13 years of age and over [female])
  • No greater than 1.5 mg/dL (13-15 years of age [male])
  • No greater than 1.7 mg/dL (16 years of age and over [male])
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • ALT ≤ 110 U/L
  • Albumin ≥ 2 g/dL
  • Normal 12-lead EKG with corrected QTc < 450 msec AND meets 1 of the following criteria:
  • Shortening fraction normal
  • Ejection fraction normal
  • No evidence of dyspnea at rest
  • No exercise intolerance
  • Pulse oximetry > 94% if there is a clinical indication for determination
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No uncontrolled infection
  • No swallowing dysfunction that would prevent taking an oral or liquid medication
  • See Disease Characteristics
  • Recovered from prior chemotherapy, immunotherapy, or radiotherapy
  • No myelosuppressive chemotherapy within the past 3 weeks (6 weeks for nitrosoureas)
  • At least 7 days since prior growth factors
  • At least 14 days since prior pegfilgrastim
  • At least 7 days since prior biologic agents
  • At least 2 weeks since prior local small-port palliative radiotherapy
  • At least 3 months since prior total-body irradiation, craniospinal radiation, or radiation to ≥ 50% of the pelvis
  • At least 6 weeks since other prior substantial bone marrow radiation
  • At least 3 months since prior stem cell transplantation
  • Hydroxyurea cytoreduction for Ph+ leukemia allowed provided it is discontinued 24 hours before first dose of dasatinib
  • Prior intrathecal (IT) therapy allowed (for patients with CNS-positive leukemia)
  • Concurrent IT therapy comprising hydrocortisone, cytarabine, methotrexate, or cytarabine (liposomal) allowed (for patients with CNS-positive leukemia)
  • No other concurrent investigational drugs
  • No other concurrent anticancer agents, including chemotherapy, radiotherapy, immunotherapy, or biologic therapy
  • No concurrent enzyme-inducing anticonvulsants, including any of the following:
  • Phenytoin
  • Phenobarbital
  • Carbamazepine
  • Felbamate
  • Primdone
  • Oxcarbazepine
  • No concurrent antithrombotic or antiplatelet agents, including any of the following:
  • Warfarin
  • Heparin
  • Low-molecular weight heparin
  • Aspirin
  • Ibuprofen
  • Other nonsteroidal anti-inflammatory drugs
  • No concurrent CYP3A4 inhibitors, including itraconazole, ketoconazole, and voriconazole
  • No concurrent highly active antiretroviral treatment for HIV-positive patients

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Children's Oncology Group

    Arcadia, California, 91006-3776

Other trials in United States

About this study

Official title: A Phase I Study of BMS-354825 (Dasatinib) in Children With Recurrent/Refractory Solid Tumors or Imatinib Resistant Ph+ Leukemia (BMS Trial CA180038)

This phase I trial is studying the side effects and best dose of dasatinib in treating young patients with recurrent or refractory solid tumors or Philadelphia chromosome-positive acute lymphoblastic leukemia or chronic myelogenous leukemia that did not respond to imatinib mesylate. Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine the toxicities and estimate the maximum tolerated dose or the recommended phase 2 dose of dasatinib in pediatric patients with refractory solid tumors.

II. Determine the toxicities of dasatinib in pediatric patients with imatinib mesylate-resistant Philadelphia chromosome-positive (Ph+) leukemia.

III. Characterize the pharmacokinetics of dasatinib in pediatric patients with refractory solid tumors or imatinib-resistant Ph+ leukemia.

SECONDARY OBJECTIVES:

  1. Preliminarily define the antitumor activity of dasatinib in pediatric patients with refractory solid tumors within the confines of a phase I study.

II. Obtain pilot data on the activity of dasatinib administered in pediatric patients with Ph+ leukemia.

III. Assess the biologic activity of dasatinib on tumor cells when available. IV. Determine the phosphotyrosine state of SRC and ABL substrates and correlate this with dasatinib dosage and antitumor activity (pharmacodynamics study).

OUTLINE: This is a multicenter, dose-escalation study. Patients are stratified according to disease (solid tumors vs leukemia).

Stratum 1 (solid tumors): Patients receive oral dasatinib twice daily on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of dasatinib 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 toxicity (DLT).

Stratum 2 (leukemia): Patients receive dasatinib as in stratum 1. Cohorts of 3-12 patients receive escalating or de-escalating doses of dasatinib. The MTD is defined as the dose preceding that at which 7 of 12 patients experience DLT.

After completing study treatment, patients are followed for 1 month.

Being tested
dasatinib, pharmacological study, laboratory biomarker analysis
Medical subject headings
Leukemia, Myeloid, Accelerated Phase, Blast Crisis, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

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

  • dasatinibDrug

    Also called BMS-354825, Sprycel

    Given orally

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT00316953
Study groupRoleWhat they receive
Stratum 1 (solid tumors)ExperimentalPatients receive oral dasatinib twice daily on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
Receives: Drug: dasatinib; Other: pharmacological study; Other: laboratory biomarker analysis
Stratum 2 (leukemia)ExperimentalPatients receive dasatinib as in stratum 1. Cohorts of 3-12 patients receive escalating or de-escalating doses of dasatinib. The MTD is defined as the dose preceding that at which 7 of 12 patients experience DLT.
Receives: Drug: dasatinib; Other: pharmacological study; Other: laboratory biomarker analysis

What is being measured

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

  1. Maximum tolerated dose defined as the maximum dose at which fewer than 1/3 patients experience dose-limiting toxicities (DLT) graded according to CTCAE

    Measured: 28 days

  2. Time to disease progression

    Will be estimated separately for patients on the solid tumor and on the refractory Ph+ leukemia strata with the Kaplan Meier method.

    Measured: Interval from enrollment to disease progression, death, occurrence of a second malignant neoplasm or last patient contact, assessed up to 1 month

Timeline

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

  1. First posted21 Apr 2006 (estimated)
  2. Study startMar 2006
  3. Primary completionSep 2009

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
48 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00316953
Sponsor's protocol ID
NCI-2012-01824
Other IDs
ADVL0516, U10CA97452, CDR0000467233
Status last verified
Jan 2013
First submitted
19 Apr 2006
Last updated
5 Feb 2013
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing dasatinib, pharmacological study and laboratory biomarker analysis in people with Accelerated Phase Chronic Myelogenous Leukemia and Blastic Phase Chronic Myelogenous Leukemia, 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 84 inclusion and 0 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 5 Feb 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 defined as the maximum dose at which fewer than 1/3 patients experience dose-limiting toxicities (DLT) graded according to CTCAE (time frame: 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00316953.

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 5 Feb 2013.

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