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Refractory Chronic Lymphocytic LeukemiaPhase 2NCT01441882

Dasatinib in Treating Patients With Chronic Lymphocytic Leukemia

A Phase 2 study testing Dasatinib, Laboratory Biomarker Analysis and Pharmacological Study in people with Refractory Chronic Lymphocytic Leukemia and Stage I Chronic Lymphocytic Leukemia, run by OHSU Knight Cancer Institute at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This phase II trial studies how well dasatinib works in treating patients with chronic lymphocytic leukemia (CLL). Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Dasatinib, Laboratory Biomarker Analysis and Pharmacological Study
Could I receive a placebo?
No, everyone receives an active treatment
How many people
19 participants
Where
1 siteUnited States
Study dates
Oct 2011to 1 Jan 2018
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal information
  • Eastern Cooperative Oncology Group (ECOG) =< 2
  • In vitro dasatinib sensitivity (IC 50 =< 50 nm per MTS assay)
  • Diagnosis of CLL and must meet one of the following:
  • Relapsed CLL in all patients who have failed at least one prior treatment, regardless of risk group
  • OR De novo (treatment-naïve) patients age >= 65 who are not candidates for or do not want to pursue aggressive chemotherapy treatment
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  • Have indications for treatment or evidence of progressive disease defined as follows (1996 NCI working group):
  • Massive or progressive splenomegaly
  • Massive lymph nodes (>= 10 cm), nodal clusters (>= 10 cm), or progressive lymphadenopathy
  • Symptomatic anemia and/or thrombocytopenia (Rai stages III or IV disease)
  • Autoimmune hemolytic anemia and/or thrombocytopenia that are poorly responsive to corticosteroid therapy
  • Progressive lymphocytosis with increase in lymphocyte count of >= 50% over a 2-month period or an anticipated doubling time of < 6 months
  • Repeated episodes of infection
  • Have not received CLL treatment within the past 2 weeks
  • Total bilirubin < 2.0 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) =< 2.5 x ULN
  • Alanine aminotransferase (ALT) =< 2.5 x ULN
  • Serum creatinine < 2.0 x ULN
  • International normalized ratio (INR) =< 1.2
  • Platelet (Plt) count > 30,000
  • Ability to take oral medication (dasatinib must be swallowed whole)
  • No clinically significant infections as determined by the investigator
  • Normal corrected QT (QTc) interval (< 450 msec)
  • Serum potassium and magnesium are within normal limits
  • Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (sensitivity =< 25 IU HCG/L) within 72 hours prior to the start of study drug administration
  • Persons of reproductive potential must agree to use an adequate method of contraception throughout treatment and for at least 4 weeks after study drug is stopped prior to study enrollment; women of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy
  • After consent, discontinuation ("washout period") of any medications known to contribute significantly to the risk of QT prolongation or interfere with cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) mediated drug metabolism
  • Patient agrees to discontinue St. John's Wort while receiving dasatinib therapy (discontinue St. John's Wort at least 5 days before starting dasatinib)
  • Patient agrees that IV bisphosphonates will be withheld for the first eight weeks of dasatinib therapy due to risk of hypocalcemia
  • Patient agrees to discontinue anti-coagulants and anti-platelet drugs; note: a low dose aspirin regimen (81mg QD) is permitted with close monitoring of the subject's platelets for a level >= 50,000/mm^3

Who cannot join

  • Patients may not receive concurrent chemotherapy, radiotherapy, or immunotherapy
  • Pleural or pericardial effusion of any grade
  • Uncontrolled angina, > New York Heart Association (NYHA) class III congestive heart failure or myocardial infarction (MI) within 6 months prior to study enrollment
  • 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)
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  • Subjects who are detained or imprisoned are not eligible
  • 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)
  • May not take concomitant medications 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, sparfloxacin, lidoflazine
  • Patients already taking other CYP inducers or inhibitors other than those listed above are eligible for the study only after principal investigator (PI) review; dose adjustments and/or monitoring of drug levels where applicable will be made as needed by the PI after consultation with pharmacy
  • Women 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 cessation of study drug, or
  • Have a positive pregnancy test at baseline, or
  • Are pregnant or breastfeeding

Trial locations and contacts

1 site in 1 country.

United States1 site

  • OHSU Knight Cancer Institute

    Portland, Oregon, 97239

Other trials in United States

About this study

Official title: A Phase II Study of Dasatinib in Chronic Lymphocytic Leukemia in Patients Who Exhibit in Vitro Dasatinib Sensitivity

This phase II trial studies how well dasatinib works in treating patients with chronic lymphocytic leukemia (CLL). Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To estimate the biologic target activity of dasatinib in CLL patients found to have pre-treatment in vitro dasatinib cytotoxicity (as defined by a >= 50% decrease in absolute lymphocyte count and/or bone marrow CLL count and/or lymph node or spleen size).

SECONDARY OBJECTIVES:

  1. To evaluate overall objective response rates per CLL National Cancer Institute (NCI) working group.

II. To determine drug safety and tolerability of dasatinib in patients with CLL.

III. To determine overall (OS) and progression-free survival (PFS).

TERTIARY OBJECTIVES:

  1. To determine if v-src avian sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (SRC), Bruton agammaglobulinemia tyrosine kinase (BTK), or tec protein tyrosine kinase (TEC) family kinase inhibition correlates with clinical response.

II. To determine which prognostic subgroups (presence of >= 1 of the following: 11q or 17p deletion; cluster of differentiation [CD]38 or zeta-chain-associated protein kinase 70 [Zap 70] expression; unmutated immunoglobulin heavy chain [IgVH]) respond to dasatinib therapy.

III. To evaluate differences in baseline CLL gene expression between CLL samples that are sensitive or in-sensitive to dasatinib.

IV. To analyze changes in CLL gene expression after dasatinib treatment. V. To evaluate dasatinib pharmacokinetics. VI. To evaluate changes in type I receptor tyrosine kinase-like orphan receptor (ROR-1) expression with dasatinib treatment.

VII. To correlate response to pre-clinical IC50 in the presence/absence of HS-5 conditioned media.

VIII. To explore role of possible kinase mutations related to dasatinib response.

IX. To measure chemokines before and during treatment.

OUTLINE:

Patients receive dasatinib orally (PO) once daily (QD) during course 1 and if tolerated, twice daily (BID) in subsequent courses. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 2 years.

Being tested
Dasatinib, Laboratory Biomarker Analysis, Pharmacological Study
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DasatinibDrug

    Also called BMS-354825, Sprycel

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacological StudyOther

    Correlative studies

Study groups in NCT01441882
Study groupRoleWhat they receive
Treatment (dasatinib)ExperimentalPatients receive dasatinib PO QD during course 1 and if tolerated, BID in subsequent courses. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Dasatinib; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The Number of Participants With In Vitro Dasatinib Sensitivity in Predicting Clinical Activity

    Defined by a decrease in absolute lymphocyte count, as determined by peripheral blood complete blood count (CBC) with differential or by bone marrow examination of 50 % and/or a decrease of detectable total lymph node size or spleen size by 50% (either by clinical examination contrast enhanced computed tomography [CT]).

    Measured: 8 weeks

Secondary outcomes (4)

  1. Objective Response

    Proportion of patients achieving the endpoint along with its 95% exact binomial confidence interval will be presented. Complete Response (CR): present >=2 mos: no symptoms of CLL, normal findings on exam, ALC < 4.000/mm3, ANC >1.500/ mm3, platelet (PLT) count (ct) >100.000/ mm3, hemoglobin (Hgb) concentration >11 g/dL (untransfused), bone marrow (BM) lymphocytosis <30%, and no nodules (lymphoid aggregates) on BM biopsy. Partial Response (PR): present >=2 months: a reduction in prev. enlarged nodes, spleen, \& liver by at least 50%. ANC >= 1.500/ mm3 or PLT ct >= 100.000/ mm3 or Hgb concentration >=11 g/dL or 50% improvement over pre-therapy reductions in Hgb concentration and/or PLT ct. Nodular PR: persistent BM nodules or infiltrates seen on BM biopsy those achieving a CR or PR. Stable Disease (SD): Does not meet CR or PR, but also not progressive disease (PD). PD: 50% size increase of lymph node, spleen, liver; or histologic (e.g. Richter's) transformation (per NCI and iwCLL).

    Measured: Up to 2 years

  2. Overall Survival

    Kaplan-Meier method will be used to estimate the survival curve.

    Measured: Up to 2 years

  3. Progression-free Survival

    Kaplan-Meier method will be used to estimate the survival curve.

    Measured: Up to 2 years

  4. Incidence of Adverse Events (Number of Participants Affected)

    Assessed According to the NCI Common Terminology Criteria for Adverse Events Version 4.0. Adverse events will be tabulated and summarized according to key reporting criteria (i.e., grade or seriousness, unanticipated, treatment attribution). Refer to the Adverse Event tables below for specific details.

    Measured: Up to 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Sep 2011 (estimated)
  2. Study startOct 2011
  3. Primary completion12 Jul 2016
  4. Study completion1 Jan 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01441882
Sponsor's protocol ID
IRB00006146
Other IDs
NCI-2011-03136, HEM 10010-L, OHSU-6146, BMS CA180-280, IRB00006146
Status last verified
Mar 2021
First submitted
21 Sep 2011
Last updated
8 Apr 2021
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Dasatinib, Laboratory Biomarker Analysis and Pharmacological Study in people with Refractory Chronic Lymphocytic Leukemia and Stage I Chronic Lymphocytic Leukemia, run by OHSU Knight Cancer Institute at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 30 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Feb 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The Number of Participants With In Vitro Dasatinib Sensitivity in Predicting Clinical Activity (time frame: 8 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01441882.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Apr 2021.

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