Dasatinib for Immune Modulation After Donor Stem Cell Transplant for Hematologic Malignancies

NCT ID: NCT01643603

Last Updated: 2020-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

5 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-05-31

Study Completion Date

2018-10-09

Brief Summary

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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.

Detailed Description

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This is a phase I, dose-escalation study.

Conditions

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Non-Hodgkin's Lymphoma Hodgkin's Lymphoma Myeloid Leukemia Multiple Myeloma Myelodysplastic Syndrome Lymphoid Leukemia

Keywords

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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 hepatosplenic T-cell lymphoma intraocular lymphoma nodal marginal zone B-cell lymphoma noncontiguous stage II adult Burkitt lymphoma noncontiguous stage II adult diffuse large cell lymphoma noncontiguous stage II adult diffuse mixed cell lymphoma noncontiguous stage II adult diffuse small cleaved cell lymphoma noncontiguous stage II adult immunoblastic large cell lymphoma noncontiguous stage II adult lymphoblastic lymphoma noncontiguous stage II grade 1 follicular lymphoma noncontiguous stage II grade 2 follicular lymphoma noncontiguous stage II grade 3 follicular lymphoma noncontiguous stage II mantle cell lymphoma noncontiguous stage II marginal zone lymphoma noncontiguous stage II small lymphocytic lymphoma noncutaneous extranodal lymphoma peripheral T-cell lymphoma previously treated myelodysplastic syndromes recurrent adult acute lymphoblastic leukemia recurrent adult acute myeloid leukemia recurrent adult Burkitt lymphoma recurrent adult diffuse large cell lymphoma recurrent adult diffuse mixed cell lymphoma recurrent adult diffuse small cleaved cell lymphoma recurrent adult grade III lymphomatoid granulomatosis recurrent adult Hodgkin lymphoma recurrent adult immunoblastic large cell lymphoma recurrent adult lymphoblastic lymphoma recurrent adult T-cell leukemia/lymphoma recurrent cutaneous T-cell non-Hodgkin lymphoma recurrent grade 1 follicular lymphoma recurrent grade 2 follicular lymphoma recurrent grade 3 follicular lymphoma recurrent mantle cell lymphoma recurrent marginal zone lymphoma recurrent mycosis fungoides/Sezary syndrome recurrent small lymphocytic lymphoma refractory chronic lymphocytic leukemia refractory hairy cell leukemia relapsing chronic myelogenous leukemia small intestine lymphoma splenic marginal zone lymphoma stage I adult Burkitt lymphoma stage I adult diffuse large cell lymphoma stage I adult diffuse mixed cell lymphoma stage I adult diffuse small cleaved cell lymphoma stage I adult Hodgkin lymphoma stage I adult immunoblastic large cell lymphoma stage I adult lymphoblastic lymphoma stage I adult T-cell leukemia/lymphoma stage I chronic lymphocytic leukemia stage I cutaneous T-cell non-Hodgkin lymphoma stage I grade 1 follicular lymphoma stage I grade 2 follicular lymphoma stage I grade 3 follicular lymphoma stage I mantle cell lymphoma stage I marginal zone lymphoma stage I small lymphocytic lymphoma stage IA mycosis fungoides/Sezary syndrome stage IB mycosis fungoides/Sezary syndrome stage II adult Hodgkin lymphoma stage II chronic lymphocytic leukemia stage II cutaneous T-cell non-Hodgkin lymphoma stage IIA mycosis fungoides/Sezary syndrome stage IIB mycosis fungoides/Sezary syndrome stage III adult Burkitt lymphoma stage III adult diffuse large cell lymphoma stage III adult diffuse mixed cell lymphoma stage III adult diffuse small cleaved cell lymphoma stage III adult Hodgkin lymphoma stage III adult immunoblastic large cell lymphoma stage III adult lymphoblastic lymphoma stage III adult T-cell leukemia/lymphoma stage III chronic lymphocytic leukemia stage III cutaneous T-cell non-Hodgkin lymphoma stage III grade 1 follicular lymphoma stage III grade 2 follicular lymphoma stage III grade 3 follicular lymphoma stage III mantle cell lymphoma stage III marginal zone lymphoma stage III small lymphocytic lymphoma stage IIIA mycosis fungoides/Sezary syndrome stage IIIB mycosis fungoides/Sezary syndrome stage IV adult Burkitt lymphoma stage IV adult diffuse large cell lymphoma stage IV adult diffuse mixed cell lymphoma stage IV adult diffuse small cleaved cell lymphoma stage IV adult Hodgkin lymphoma stage IV adult immunoblastic large cell lymphoma stage IV adult lymphoblastic lymphoma stage IV adult T-cell leukemia/lymphoma stage IV chronic lymphocytic leukemia stage IV cutaneous T-cell non-Hodgkin lymphoma stage IV grade 1 follicular lymphoma stage IV grade 2 follicular lymphoma stage IV grade 3 follicular lymphoma stage IV mantle cell lymphoma stage IV marginal zone lymphoma stage IV small lymphocytic lymphoma stage IVA mycosis fungoides/Sezary syndrome stage IVB mycosis fungoides/Sezary syndrome T-cell large granular lymphocyte leukemia testicular lymphoma Waldenström macroglobulinemia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Dasatinib

Intervention Type DRUG

Patients receive dasatinib PO every day (QD) for 6 months.

laboratory biomarker analysis

Intervention Type OTHER

Correlative studies

Interventions

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Dasatinib

Patients receive dasatinib PO every day (QD) for 6 months.

Intervention Type DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type OTHER

Other Intervention Names

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BMS-354825 Sprycel

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Barbara Ann Karmanos Cancer Institute

OTHER

Sponsor Role lead

Responsible Party

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Abhinav Deol

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Abhinav Deol, M.D.

Role: PRINCIPAL_INVESTIGATOR

Barbara Ann Karmanos Cancer Institute

Locations

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Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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2011-204

Identifier Type: -

Identifier Source: org_study_id