Dasatinib in Treating Patients With Hematologic Malignancies Previously Treated With Donor Stem Cell Transplant
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Purpose
This study uses a drug called dasatinib to produce an anti-cancer effect called large granular lymphocyte cellular expansion. Large granular lymphocytes are blood cells known as natural killer cells that remove cancer cells. Researchers think that dasatinib may cause large granular lymphocyte expansion to happen in patients who have received a blood stem cell transplant (SCT) between 3 to 15 months after the SCT. In this research study, researchers want to find how well dasatinib can be tolerated, the best dose to take of dasatinib and how to estimate how often large granular lymphocytic cellular expansion happens at the best dose of dasatinib.
| Condition | Intervention | Phase |
|---|---|---|
|
Non-Hodgkin's Lymphoma Hodgkin's Lymphoma Myeloid Leukemia Multiple Myeloma Myelodysplastic Syndrome Lymphoid Leukemia |
Drug: Dasatinib Other: laboratory biomarker analysis |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Phase I/II Study of Dasatinib in Recipients of Allogeneic Stem Cell Transplantation for Hematologic Malignancies. |
- Maximum tolerated dose (MTD) and Dose limiting toxicity (DLT) of dasatinib [ Time Frame: 2 months ] [ Designated as safety issue: Yes ]
- Estimate the non-DLTs associated with administration of dasatinib in allogeneic stem cell transplantation (ASCT) recipients [ Time Frame: Up to 6 months post treatment ] [ Designated as safety issue: Yes ]
- Estimate the incidence of large granular lymphocytosis (LGL) and its clinical course in recipients of ASCT [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
- Perform correlative in vitro studies to see if the large granular lymphocytes show enhanced cytotoxicity to leukemia/ lymphoma cell lines [ Time Frame: Prior to day 1 administration of dasatinib and thereafter every 4 weeks ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 30 |
| Study Start Date: | May 2012 |
| Estimated Study Completion Date: | December 2015 |
| Estimated Primary Completion Date: | October 2015 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Dasatinib
This is a phase 1 dose escalation study, using a standard 3+3 design. Dasatinib is administered orally once daily in the outpatient setting. Patients who are day 100-180 post transplant will be eligible. The treatment will be started as close to day 100 as possible. The range of days is provided to ensure that patients have recovered from toxicities associated with ASCT and are not deemed ineligible if they were recovering from any toxicity associated with ASCT at day 100.The starting dose of dasatinib is 20 mg daily. The increment of dose escalation is 20 mg per dose level. Thus, there will be 5 dose levels (20 mg, 40 mg, 60 mg, 80 mg and 100 mg, respectively) with 3 patients in each cohort. Patients will continue on dasatinib for 6 months.
|
Drug: Dasatinib
Patients receive dasatinib PO every day (QD) for 6 months.
Other Names:
Other: laboratory biomarker analysis
Correlative studies
|
Detailed Description:
This is a phase I, dose-escalation study followed by a phase II study.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Recipients of first ASCT from related or unrelated donor for the treatment of hematologic malignancies (acute myeloid leukemia, chronic myeloid leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, myelodysplastic syndrome, Hodgkin and non-Hodgkin lymphoma) who are 1-antigen or 1-allele mismatched or fully matched at human leukocyte antigen (HLA)-A, -B, -C and -DR as defined by high resolution typing
- Patients must be between 100 - 180 days after allogeneic stem cell transplantation
- Dasatinib use prior to ASCT is allowed
- Performance status >= 60%
- Presence of large granular lymphocyte (LGL) clone prior to enrollment will not be an exclusion criterion if the LGL clone is < 25% of T cell population
- Total bilirubin < 2.0 times the institutional upper limit of normal (ULN)
- Hepatic enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT] ) =< 2.5 times the institutional ULN
- Serum creatinine < 1.5 time the institutional ULN
- Hemoglobin >= 8 g/dL
- Absolute neutrophil count 1,500 cells per uL
- Platelets >= 100,000 per uL
Patient should be able to provide signed written informed consent:
- Before any study procedures are performed, subjects will have the details of the study described to them, and they will be given a written informed consent document to read; then, if subjects consent to participate in the study, they will indicate that consent by signing and dating the informed consent document in the presence of study personnel
- Written consent will include a Health Insurance Portability and Accountability Act (HIPAA) form according to institutional guidelines
- Patient should be able to take oral medication (dasatinib must be swallowed whole)
Exclusion Criteria:
- Recipient of mismatched (allele or antigen level) graft in more than one loci of HLAA, -B, -C or -DR loci will not be eligible, i.e. recipients of 2-antigen or 2-allelele mismatched graft
- Patients on investigational therapy for graft-versus-host disease (GVHD)
- Patients with uncontrolled acute or chronic GVHD or refractory disease not responding to conventional therapy
- Patients who have evidence of disease progression before day 100 after ASCT
- Women of childbearing potential (WOCBP) who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 4 weeks after the last dose of study drug
- Women who are pregnant or breastfeeding
- Women with a positive pregnancy test
- Sexually active fertile men not using effective birth control if their partners are WOCBP
- No malignancy [other than the one treated in this study] which required radiotherapy or systemic treatment within the past 5 years
Concurrent medical condition which may increase the risk of toxicity, including:
- Pleural or pericardial effusion of any grade at the time of screening for study
Cardiac Symptoms; any of the following should be considered for exclusion:
- Uncontrolled angina, congestive heart failure or myocardial infarction (MI) within (6 months)
- Diagnosed congenital long QT syndrome
- Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
- Prolonged QTc interval on pre-entry electrocardiogram (> 450 msec)
History of significant bleeding disorder unrelated to cancer, including:
- Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)
- Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)
- Ongoing or recent (=< 3 months) significant gastrointestinal bleeding
- Any previous history of >= grade 3 toxicity to Dasatinib
Prohibited treatments and or therapies:
Category I drugs that are generally accepted to have a risk of causing Torsades de Pointes including: (Patients must discontinue drug 7 days prior to starting dasatinib)
- Quinidine, procainamide, disopyramide
- Amiodarone, sotalol, ibutilide, dofetilide
- Erythromycin, clarithromycin
- Chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide
- Cisapride, bepridil, droperidol, methadone, arsenic, chloroquine,
- Domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine
- Patient agrees to discontinue St. Johns Wort while receiving dasatinib therapy (discontinue St. Johns Wort at least 5 days before starting dasatinib)
- Patient agrees that IV bisphosphonates will be withheld for the first 8 weeks of dasatinib therapy due to risk of hypocalcemia
- Prisoners or subjects who are involuntarily incarcerated
- Subjects who are compulsorily detained for treatment of either a psychiatric or physical (egg, infectious disease) illness
Contacts and Locations| Contact: Abhinav Deol, M.D. | 313-576-8711 | deola@karmanos.org |
| United States, Michigan | |
| Barbara Ann Karmanos Cancer Institute | Recruiting |
| Detroit, Michigan, United States, 48201 | |
| Contact: Clinical Trials Office 800-527-6266 | |
| Sub-Investigator: Muneer Abidi, M.D. | |
| Sub-Investigator: Zaid Al-Kadhimi, M.D. | |
| Sub-Investigator: Lois Ayash, M.D. | |
| Sub-Investigator: Lawrence Lum, M.D. | |
| Sub-Investigator: Voravit Ratanatharathorn, M.D. | |
| Sub-Investigator: Charles Schiffer, M.D. | |
| Sub-Investigator: Joseph Uberti, M.D. | |
| Principal Investigator: | Abhinav Deol, M.D. | Barbara Ann Karmanos Cancer Institute |
More Information
No publications provided
| Responsible Party: | Abhinav Deol, Principal Investigator, Barbara Ann Karmanos Cancer Institute |
| ClinicalTrials.gov Identifier: | NCT01643603 History of Changes |
| Other Study ID Numbers: | 2011-204 |
| Study First Received: | May 30, 2012 |
| Last Updated: | February 25, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Barbara Ann Karmanos Cancer Institute:
|
accelerated phase chronic myelogenous leukemia adult acute lymphoblastic leukemia in remission adult acute myeloid leukemia in remission adult acute myeloid leukemia with 11q23 (MLL) abnormalities adult acute myeloid leukemia with del(5q) 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 grade III lymphomatoid granulomatosis adult nasal type extranodal NK/T-cell lymphoma anaplastic large cell lymphoma angioimmunoblastic T-cell lymphoma blastic phase chronic myelogenous leukemia chronic phase chronic myelogenous leukemia |
contiguous stage II adult Burkitt lymphoma contiguous stage II adult diffuse large cell lymphoma contiguous stage II adult diffuse mixed cell lymphoma contiguous stage II adult diffuse small cleaved cell lymphoma contiguous stage II adult immunoblastic large cell lymphoma contiguous stage II adult lymphoblastic lymphoma contiguous stage II grade 1 follicular lymphoma contiguous stage II grade 2 follicular lymphoma contiguous stage II grade 3 follicular lymphoma contiguous stage II mantle cell lymphoma contiguous stage II marginal zone lymphoma contiguous stage II small lymphocytic lymphoma cutaneous B-cell non-Hodgkin lymphoma de novo myelodysplastic syndromes extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue |
Additional relevant MeSH terms:
|
Hodgkin Disease Leukemia Leukemia, Lymphoid Leukemia, Myeloid Lymphoma Lymphoma, Non-Hodgkin Multiple Myeloma Neoplasms, Plasma Cell Myelodysplastic Syndromes Preleukemia Lymphoma, Large-Cell, Immunoblastic Hematologic Neoplasms Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders |
Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Bone Marrow Diseases Precancerous Conditions Neoplasms by Site Dasatinib Protein Kinase Inhibitors |
ClinicalTrials.gov processed this record on June 18, 2013