Dasatinib and Vorinostat in Treating Patients With Accelerated Phase or Blastic Phase Chronic Myelogenous Leukemia or Acute Lymphoblastic Leukemia

NCT00816283 | Completed Phase 1 DMC

• 4 other identifiers: 08047P30CA033572CHNMC-08047CDR0000631569
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 2

Brief Summary

RATIONALE: Dasatinib and vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving dasatinib together with vorinostat may kill more cancer cells. PURPOSE: This phase I trial is studying the side effects and best dose of dasatinib when given together with vorinostat in treating patients with accelerated phase or blastic phase chronic myelogenous leukemia or acute lymphoblastic leukemia.

Conditions

Leukemia

Keywords

accelerated phase chronic myelogenous leukemia; blastic phase chronic myelogenous leukemia; relapsing chronic myelogenous leukemia; Philadelphia chromosome positive adult precursor acute lymphoblastic leukemia; recurrent adult acute lymphoblastic leukemia; untreated adult acute lymphoblastic leukemia

Outcome Measures

Primary Outcomes (7)

• Maximum tolerated dose

  21 days after the beginning of treatment

• Toxicity as assessed by NCI CTCAE v3.0

  21 days from the beginning of the last course of treatment

• Response rate

  One year after treatment completion

• Objective tumor response

  One year after treatment completion

• Survival

  One year after treatment completion

• Time to treatment failure

  One year after treatment completion

• Duration of response

  One year after treatment completion

Interventions

dasatinib DRUG

50 mg orally 2 times per day or 140 mg orally one time per day

vorinostat DRUG

100 mg orally 2 times per day

cytogenetic analysis GENETIC

Performed at the end of cycle two of treatment and every six cycles for patients with accelerated CML and every 3 cycles for patients with blast crisis or Ph+ ALL

gene expression analysis GENETIC

Bone marrow aspirate obtained pre-treatment, at first scheduled bone marrow assay and at relapse. Peripheral blood drawn pre-therapy, day +14 of first treatment cycle and at relapse.

mutation analysis GENETIC

Performed at baseline and at every bone marrow analysis on peripheral blood

reverse transcriptase-polymerase chain reaction GENETIC

Peripheral blood drawn prior to starting Vorinostat on Day 1 and on Day 14 of treatment

flow cytometry OTHER

Performed at the end of cycle two of treatment and every six cycles for patients with accelerated CML and every 3 cycles for patients with blast crisis or Ph+ ALL

laboratory biomarker analysis OTHER

Performed pre-treatment and day +14 of treatment

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Diagnosis of 1 of the following hematologic malignancies: * Chronic myelogenous leukemia meeting 1 of the following criteria: * In accelerated phase, defined by the presence of ≥ 1 of the following: * At least 15% but \< 30% blasts in peripheral blood and/or bone marrow * At least 30% blasts plus promyelocytes in peripheral blood or bone marrow (providing that \< 30% blasts are present in bone marrow) * At least 20% basophils in peripheral blood * Platelet count \< 100,000/mm³ (unrelated to therapy) OR platelet count \> 100,000/mm³ and unresponsive to therapy * Cytogenetic evidence of clonal evolution * Increasing spleen size and increasing WBC count and unresponsive to therapy * In blastic phase (blast crisis), defined by the presence of ≥ 1 of the following: * At least 30% blasts in peripheral blood and/or bone marrow * Extramedullary infiltrates of leukemic cells (other than liver or spleen involvement) * Philadelphia chromosome-positive acute lymphoblastic leukemia meeting any of the following criteria: * Newly diagnosed or relapsed disease * Previously treated with chemotherapy, stem cell transplantation, or tyrosine kinase inhibitors (TKIs) * No active CNS involvement PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * Total bilirubin \< 2.0 times upper limit of normal (ULN) * AST and ALT ≤ 2.5 times ULN * Serum sodium, potassium, magnesium, phosphate, and calcium ≥ lower limit of normal * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for ≥ 4 weeks after discontinuation of study drug * Able to take oral medication * No active post-transplantation-related infections (e.g., fungal or viral infection) * No active acute graft-versus-host disease (GVHD) of any grade * No chronic GVHD (other than mild skin, oral, or ocular GVHD not requiring systemic immunosuppression) * No other malignancy that required radiotherapy or systemic treatment within the past 5 years * No concurrent medical condition that may increase the risk of toxicity, including pleural or pericardial effusion of any grade * No cardiac conditions, including any of the following: * Uncontrolled angina, congestive heart failure, or myocardial infarction within the past 6 months * Diagnosed congenital long QT syndrome * History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, or Torsades de pointes) * Prolonged QTc interval (i.e., QTc \> 450 msec) on baseline EKG * No hypokalemia or hypomagnesemia that cannot be corrected prior to dasatinib administration * No history of significant bleeding disorder unrelated to cancer, including any of the following: * Diagnosed congenital bleeding disorder (e.g., von Willebrand's disease) * Acquired bleeding disorder diagnosed within the past year (e.g., acquired anti-factor VIII antibodies) * Ongoing or recent (i.e., within the past 3 months) significant gastrointestinal bleeding * No prisoners or individuals who are compulsorily detained (i.e., involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness PRIOR CONCURRENT THERAPY: * See Disease Characteristics * Recovered from prior therapy * No prior HDAC inhibitors or compounds with HDAC inhibitor-like activity (e.g., valproic acid) as anti-tumor therapy * Prior valproic acid for the treatment of seizures allowed provided it was not given within the past 30 days * Prior allogeneic stem cell transplantation allowed * More than 4 weeks since prior chemotherapy other than TKI (6 weeks for nitrosoureas and mitomycin) * More than 2 weeks since prior radiotherapy * At least 7 days since prior and no concurrent Category I drugs that are generally accepted to have a risk of causing Torsades de pointes, including any of the following: * Quinidine, procainamide, or disopyramide * Amiodarone, sotalol, ibutilide, or dofetilide * Erythromycin or clarithromycin * Chlorpromazine, haloperidol, mesoridazine, thioridazine, or pimozide * Cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, or lidoflazine * At least 7 days since prior and no concurrent medications that directly and durably inhibit platelet function, including any of the following: * Aspirin or aspirin-containing combinations, clopidogrel, or dipyridamole * Tirofiban, epoprostenol, eptifibatide, cilostazol, abciximab, ticlopidine, or cilostazol * At least 5 days since prior and no concurrent St. John's wort * No IV bisphosphonates during the first 8 weeks of dasatinib therapy

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010-3000, United States

Location

City of Hope Medical Group

Pasadena, California, 91105, United States

Location

MeSH Terms

Conditions

Leukemia; Leukemia, Myeloid, Accelerated Phase; Blast Crisis; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Dasatinib; Vorinostat; Cytogenetic Analysis; Gene Expression Profiling; Reverse Transcriptase Polymerase Chain Reaction; Flow Cytometry

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Anilides; Amides; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; Polymerase Chain Reaction; Nucleic Acid Amplification Techniques; Cell Separation; Cytophotometry; Fluorometry; Luminescent Measurements; Photometry; Chemistry Techniques, Analytical

Study Officials

• David Snyder, MD

  City of Hope Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: December 31, 2008
• First Posted: January 1, 2009
• Study Start: September 1, 2008
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2011
• Last Updated: July 17, 2012

Record last verified: 2012-07

Locations

US (2)