AzTrials
AzTrials

Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic LeukemiaPhase 1/2NCT01383447

Entinostat And Imatinib Mesylate In Treating Patients With Relapsed or Refractory Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

A Phase 1/2 study testing entinostat, imatinib mesylate and laboratory biomarker analysis in people with Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia and Recurrent Adult Acute Lymphoblastic Leukemia, run by National Cancer Institute (NCI) at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

This phase I/II trial is studying the side effects and best dose of entinostat when given together with imatinib mesylate and to see how well it works in treating patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukemia. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
entinostat, imatinib mesylate and laboratory biomarker analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2 participants
Where
1 siteUnited States
Study dates
Oct 2010to Apr 2012
Phase
Phase 1/2
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

  • Patients must have histologically confirmed BCR-ABL1 associated (Ph+) acute lymphoblastic leukemia (ALL) with primary refractory or relapsed disease; demonstration of BCR-ABL1 in leukemia cells by one or more of the following is required: t(9;22)(q34;q11.2) cytogenetics; FISH for BCR-ABL1 fusion; RT-PCR for BCR-ABL1 fusion
  • Prior treatment with tyrosine kinase inhibitors (including imatinib, nilotinib and/or dasatinib) is allowed, although patients must be off any tyrosine kinase inhibitor for a minimum of 72 hours prior to beginning protocol therapy
  • ECOG performance status of 0, 1 or 2
  • Total WBC =< 150,000 with no evidence for ongoing or impending leukostasis
  • Total bilirubin =< 2.0 mg/dL unless elevated due to Gilbert's, hemolysis or leukemic infiltration
  • Aspartate transaminase (AST)/alanine transaminase (ALT) =< 2.5 × upper limit of normal (ULN) unless due to leukemic infiltration
Show all 12Show fewer
  • Serum creatinine =< 2.0 mg/dL or creatinine clearance > 50 ml/min
  • Left ventricular ejection fraction (LVEF) >= 45% as measured by echocardiogram (ECHO) or MUGA
  • Patients who have undergone stem cell transplantation (SCT), autologous or allogeneic, are eligible provided that they are > 4 weeks from stem cell infusion, have no active GVHD, and meet other eligibility criteria
  • Patients who fail primary induction therapy or relapse after achieving complete remission (CR) are eligible if they are > 3 weeks off cytotoxic chemotherapy and > 2 weeks off radiation therapy; patients must be off biologic therapies including hematopoietic growth factors > 1 week; if using hydroxyurea (HU), steroids, or other non-cytotoxics for blast count control, patient must be off for > 24 hrs before starting protocol therapy; patients must have recovered from all acute toxicities from any previous therapy
  • Female patients of childbearing age must have negative pregnancy test; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • Patients may not be receiving any other investigational agents
  • Active CNS leukemia; patients with known previous CNS leukemia may continue to receive intrathecal therapy with ara-C, methotrexate, and/or thiotepa plus steroids as prophylaxis against reactivation of previous CNS disease
  • Patients may not have received previous treatment with entinostat or other HDAC inhibitors
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to entinostat or other agents used in study
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active untreated infection, symptomatic congestive heart failure, unstable angina pectoris, unstable cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with entinostat
  • HIV-positive patients on combination antiretroviral therapy are ineligible

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Johns Hopkins University

    Baltimore, Maryland, 21287-8936

Other trials in United States

About this study

Official title: A Phase 1/2 Study of SNDX-275 in Combination With Imatinib for Relapsed/Refractory Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

This phase I/II trial is studying the side effects and best dose of entinostat when given together with imatinib mesylate and to see how well it works in treating patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukemia. Entinostat and imatinib mesylate 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 determine the maximum tolerated dose (MTD) of entinostat when given in combination with imatinib (matinib mesylate).

SECONDARY OBJECTIVES:

  1. To estimate the rate of complete response (CR) for patients greater ≥ 18 years of age with relapsed/refractory Ph+ ALL treated with a combination of entinostat and imatinib.

II. To estimate the 1 year progression free survival (PFS) for patients greater ≥ 18 years of age with relapsed/refractory Ph+ ALL treated with a combination of entinostat and imatinib III. To describe the comparative pharmacokinetics (PK) and pharmacodynamics (PD) of entinostat when administered alone vs. in combination with imatinib.

IV. To assess the predictive value of levels of flow cytometric minimal residual disease (MRD) on duration of progression free survival for the study population.

OUTLINE: This is a phase I, dose-escalation study of entinostat followed by a phase II study.

Patients receive entinostat orally (PO) daily on days 1, 8, 15, and 22 and imatinib mesylate PO twice daily on days 1-28 (days 4-28 of course 1). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

Being tested
entinostat, imatinib mesylate, laboratory biomarker analysis, pharmacological study, western blotting
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

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

  • entinostatDrug

    Also called HDAC inhibitor SNDX-275, SNDX-275

    Given PO

  • imatinib mesylateDrug

    Also called CGP 57148, Gleevec, Glivec

    Given PO

  • laboratory biomarker analysisOther

    Correlative studies

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

  • western blottingGenetic

    Also called Blotting, Western, Western Blot

    Correlative studies

  • immunohistochemistry staining methodOther

    Also called immunohistochemistry

    Correlative studies

  • flow cytometryOther

    Correlative studies

  • polymerase chain reactionGenetic

    Also called PCR

    Correlative studies

  • high performance liquid chromatographyOther

    Also called HPLC

    Correlative studies

  • mass spectrometryOther

    Correlative studies

Study groups in NCT01383447
Study groupRoleWhat they receive
Treatment (entinostat and imatinib mesylate)ExperimentalPatients receive entinostat PO daily on days 1, 8, 15, and 22 and imatinib mesylate PO twice daily on days 1-28 (days 4-28 of course 1). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: entinostat; Drug: imatinib mesylate; Other: laboratory biomarker analysis; Other: pharmacological study; Genetic: western blotting; Other: immunohistochemistry staining method; Other: flow cytometry; Genetic: polymerase chain reaction; Other: high performance liquid chromatography; Other: mass spectrometry

What is being measured

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

  1. Maximum Tolerated Dose (MTD) of Entinostat When Given in Combination With Imatinib Mesylate

    The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.

    Measured: Up to 30 days post-treatment

Secondary outcomes (4)

  1. Rate of Complete Response (CR) for Adults With Relapsed/Refractory Ph+ ALL Treated With a Combination of Entinostat (at the Dose Determined in Phase 1) and Imatinib Mesylate

    Measured: Up to 30 days post-treatment

  2. Progression Free Survival (PFS) for Adults With Relapsed/Refractory Ph+ ALL Treated With Combination of Entinostat and Imatinib Mesylate

    The Kaplan-Meier estimator will be used to estimate PFS with a 95% confidence interval from study entry.

    Measured: At 1 year

  3. Comparative Pharmacokinetics (PK) and Pharmacodynamics (PD) of Entinostat Alone vs. Entinostat Plus Imatinib Mesylate

    Entinostat concentrations will be compared when administered alone or in combination with imatinib by paired Student's t test (day 4 vs 11 concentrations) or Wilcoxon signed rank tests as appropriate. Association between exposure parameters and PD endpoints (e.g., apoptosis, histone acetylation, BCR-ABL expression) will be assessed using Fisher's exact tests or Wilcoxon rank sum tests as appropriate.

    Measured: Day 4 and 11

  4. Predictive Values of Levels of Flow Cytometric Minimal Residual Disease (MRD) on Duration of Progression Free Survival for the Study Population

    Kaplan-Meier PFS curves and cumulative incidence of progression curves will be generated for patients above vs. below each threshold, and log rank will be used to compare the curves.

    Measured: Day 29

Timeline

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

  1. First posted28 Jun 2011 (estimated)
  2. Study startOct 2010
  3. Primary completionApr 2012
  4. Study completionApr 2012

Why it stopped: This study was halted prematurely by the NCI for low accrual.

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
2 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01383447
Sponsor's protocol ID
NCI-2010-02202
Other IDs
J1023, U01CA070095
Status last verified
Jul 2017
First submitted
5 May 2011
Last updated
8 Aug 2017

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing entinostat, imatinib mesylate and laboratory biomarker analysis in people with Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia and Recurrent Adult Acute Lymphoblastic Leukemia, run by National Cancer Institute (NCI) 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 12 inclusion and 7 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: stopped early, as of the sponsor's last update on 8 Aug 2017. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 8 Aug 2017). 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?

Maximum Tolerated Dose (MTD) of Entinostat When Given in Combination With Imatinib Mesylate (time frame: Up to 30 days post-treatment). 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 NCT01383447.

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 Aug 2017.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in