- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00316953
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 I Study of BMS-354825 (Dasatinib) in Children With Recurrent/Refractory Solid Tumors or Imatinib Resistant Ph+ Leukemia (BMS Trial CA180038)
Study Overview
Status
Conditions
- Unspecified Childhood Solid Tumor, Protocol Specific
- Accelerated Phase Chronic Myelogenous Leukemia
- Childhood Chronic Myelogenous Leukemia
- Recurrent Childhood Acute Lymphoblastic Leukemia
- Relapsing Chronic Myelogenous Leukemia
- Chronic Myelogenous Leukemia, BCR-ABL1 Positive
- Blastic Phase Chronic Myelogenous Leukemia
- Meningeal Chronic Myelogenous Leukemia
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVES:
I. 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:
I. 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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
California
-
Arcadia, California, United States, 91006-3776
- Children's Oncology Group
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
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:
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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.
|
Correlative studies
Correlative studies
Other Names:
Given orally
Other Names:
|
Experimental: 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.
|
Correlative studies
Correlative studies
Other Names:
Given orally
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
28 days
|
|
Time to disease progression
Time Frame: Interval from enrollment to disease progression, death, occurrence of a second malignant neoplasm or last patient contact, assessed up to 1 month
|
Will be estimated separately for patients on the solid tumor and on the refractory Ph+ leukemia strata with the Kaplan Meier method.
|
Interval from enrollment to disease progression, death, occurrence of a second malignant neoplasm or last patient contact, assessed up to 1 month
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Richard Aplenc, Children's Oncology Group
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Disease Attributes
- Bone Marrow Diseases
- Hematologic Diseases
- Myeloproliferative Disorders
- Neoplastic Processes
- Cell Transformation, Neoplastic
- Carcinogenesis
- Leukemia
- Leukemia, Myeloid
- Recurrence
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Leukemia, Lymphoid
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
- Blast Crisis
- Leukemia, Myeloid, Accelerated Phase
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Dasatinib
Other Study ID Numbers
- NCI-2012-01824
- ADVL0516
- U10CA97452 (Other Grant/Funding Number: US NIH Grant/Contract Award Number)
- CDR0000467233 (Registry Identifier: PDQ (Physician Data Query))
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Unspecified Childhood Solid Tumor, Protocol Specific
-
Wake Forest University Health SciencesNational Cancer Institute (NCI)RecruitingCollection and Storage of Tissue Samples From Patients Undergoing Surgery For Suspected Solid TumorsUnspecified Childhood Solid Tumor, Protocol Specific | Unspecified Adult Solid Tumor, Protocol SpecificUnited States
-
Kantonsspital GraubuendenUnknownUnspecified Childhood Solid Tumor, Protocol Specific | Unspecified Adult Solid Tumor, Protocol SpecificSwitzerland
-
National Cancer Institute (NCI)CompletedUnspecified Childhood Solid Tumor, Protocol Specific | Unspecified Adult Solid Tumor, Protocol SpecificUnited States
-
Vanderbilt UniversityNational Cancer Institute (NCI)TerminatedUnspecified Childhood Solid Tumor, Protocol Specific | Unspecified Adult Solid Tumor, Protocol SpecificUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)CompletedUnspecified Childhood Solid Tumor, Protocol Specific | Unspecified Adult Solid Tumor, Protocol SpecificUnited States
-
University of ChicagoNational Cancer Institute (NCI)CompletedSirolimus in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed By SurgeryUnspecified Childhood Solid Tumor, Protocol Specific | Unspecified Adult Solid Tumor, Protocol SpecificUnited States
-
Wake Forest University Health SciencesNational Cancer Institute (NCI)WithdrawnUnspecified Childhood Solid Tumor, Protocol Specific | Unspecified Adult Solid Tumor, Protocol Specific
-
Memorial Sloan Kettering Cancer CenterNational Cancer Institute (NCI)CompletedUnspecified Childhood Solid Tumor, Protocol Specific | Unspecified Adult Solid Tumor, Protocol SpecificUnited States
-
Rutgers, The State University of New JerseyNational Cancer Institute (NCI); Rutgers Cancer Institute of New JerseyWithdrawnUnspecified Childhood Solid Tumor, Protocol Specific | Unspecified Adult Solid Tumor, Protocol Specific | Hematopoietic/Lymphoid CancerUnited States
-
Children's Cancer and Leukaemia GroupUnknownUnspecified Childhood Solid Tumor, Protocol SpecificIreland, United Kingdom
Clinical Trials on laboratory biomarker analysis
-
Children's Oncology GroupNational Cancer Institute (NCI)Completed
-
ECOG-ACRIN Cancer Research GroupNational Cancer Institute (NCI)CompletedProstate Cancer
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Active, not recruitingLeukemia | Acute Lymphoblastic Leukemia | Acute Promyelocytic LeukemiaUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedUntreated Adult Acute Lymphoblastic Leukemia | Untreated Childhood Acute Lymphoblastic LeukemiaUnited States, Canada, Australia, New Zealand, Puerto Rico, Switzerland
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedChildhood Acute Lymphoblastic Leukemia in Remission | Recurrent Childhood Acute Lymphoblastic LeukemiaUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)CompletedLung CancerUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Completed
-
Children's Oncology GroupNational Cancer Institute (NCI)WithdrawnClear Cell Renal Cell Carcinoma | Rhabdoid Tumor of the Kidney | Congenital Mesoblastic Nephroma | Childhood Kidney NeoplasmUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)WithdrawnBreast Carcinoma | BRCA1 Mutation Carrier | BRCA2 Mutation CarrierUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedWilms Tumor and Other Childhood Kidney TumorsUnited States