Dasatinib for Modulating Immune System After Autologous Stem Cell Transplants for Multiple Myeloma, Non-Hodgkin, or Hodgkin Lymphoma

Sponsor

Barbara Ann Karmanos Cancer Institute (Other)

Overall Status

Terminated

CT.gov ID

NCT01609816

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

43.9

Actual Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

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 blood SCT. In this research study, researchers want to find how well dasatinib can be tolerated, the best dose to take of dasatinib and to estimate how often large granular lymphocytic cellular expansion happens at the best dose of dasatinib.

Condition or Disease	Intervention/Treatment	Phase
Non-Hodgkin's Lymphoma Multiple Mycosis Fungoides Hodgkin's Lymphoma Multiple Myeloma	Drug: Dasatinib	Phase 1

Detailed Description

This is a phase I, dose-escalation study.

Study Design

Study Type:

Interventional

Actual Enrollment :

8 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase I Study of Dasatinib in Recipients of Autologous Stem Cell Transplantation for Hematologic Malignancies.

Actual Study Start Date :

Feb 12, 2015

Actual Primary Completion Date :

Oct 9, 2018

Actual Study Completion Date :

Oct 9, 2018

Arms and Interventions

Arm	Intervention/Treatment
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. 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: BMS-354825 Sprycel

Arm

Intervention/Treatment

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. 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:

BMS-354825

Sprycel

Outcome Measures

Primary Outcome Measures

Dose limiting toxicity (DLT) graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4 [2 months]
Maximum tolerated dose (MTD)graded according to the NCI CTCAE version 4 [2 months]
Defined as highest dose at which no more than one of dose limiting toxicity (DLT) is observed (among the first 6 patients treated and evaluable for toxicity for the purpose of cohort dose escalation decisions).

Secondary Outcome Measures

Incidence of large granular lymphocytes (LGL) lymphocytosis [6 months]
95% confidence intervals estimated.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Recipients of first ASCT for the treatment of hematologic malignancies (multiple myeloma, Hodgkin's and non Hodgkin's lymphoma)
Patients must be between 100 to 180 days after ASCT
Dasatinib use prior to ASCT is allowed
Performance status >= 60%
Presence of 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 times the institutional ULN
Hemoglobin >= 8 g/dL
Absolute neutrophil counts >= 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:

Patients who have evidence of disease progression before day 100 after ASCT
Sex and reproductive status:
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
Medical history and concurrent diseases:
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 corrected QT (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 intravenous (IV) bisphosphonates will be withheld for the first 8 weeks of dasatinib therapy due to risk of hypocalcemia
Other exclusion criteria:
Prisoners or subjects who are involuntarily incarcerated
Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness