Study Stopped
Study terminated due to slow accrual.
Dasatinib for Immune Modulation After Donor Stem Cell Transplant for Hematologic Malignancies
Phase I Study of Dasatinib in Recipients of Allogeneic Stem Cell Transplantation for Hematologic Malignancies.
1 other identifier
interventional
5
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started May 2012
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
May 1, 2012
CompletedFirst Submitted
Initial submission to the registry
May 30, 2012
CompletedFirst Posted
Study publicly available on registry
July 18, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 9, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
October 9, 2018
CompletedDecember 17, 2020
December 1, 2020
6.4 years
May 30, 2012
December 14, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Maximum tolerated dose (MTD) and Dose limiting toxicity (DLT) of dasatinib
2 months
Secondary Outcomes (3)
Estimate the non-DLTs associated with administration of dasatinib in allogeneic stem cell transplantation (ASCT) recipients
Up to 6 months post treatment
Estimate the incidence of large granular lymphocytosis (LGL) and its clinical course in recipients of ASCT
Up to 6 months
Perform correlative in vitro studies to see if the large granular lymphocytes show enhanced cytotoxicity to leukemia/ lymphoma cell lines
Prior to day 1 administration of dasatinib and thereafter every 4 weeks
Study Arms (1)
Dasatinib
EXPERIMENTALThis 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.
Interventions
Patients receive dasatinib PO every day (QD) for 6 months.
Eligibility Criteria
You may qualify if:
- 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%
- 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)
You may not qualify if:
- 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
- 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)
- +17 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Abhinav Deol, M.D.
Barbara Ann Karmanos Cancer Institute
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
May 30, 2012
First Posted
July 18, 2012
Study Start
May 1, 2012
Primary Completion
October 9, 2018
Study Completion
October 9, 2018
Last Updated
December 17, 2020
Record last verified: 2020-12