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Acute Myeloid LeukemiaPhase 1NCT02093403

Decitabine and Selinexor in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

A Phase 1 study testing decitabine, selinexor and pharmacological study in people with Acute Myeloid Leukemia and Secondary Acute Myeloid Leukemia, run by Bhavana Bhatnagar 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
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Trial summary

This phase I trial studies the side effects and best dose of Selinexor when given together with decitabine in treating patients with acute myeloid leukemia that has returned after treatment (relapsed) or does not respond to treatment (refractory). Read more about this study

Who is it for?
Ages 19 years and older
What is being tested?
decitabine, selinexor and pharmacological study
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
1 siteUnited States
Study dates
Mar 2014to 26 Nov 2016
Phase
Phase 1
Are there results?
None posted in the registry

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

Who may be able to join

  • Patients with relapsed or refractory AML
  • Newly diagnosed elderly AML patients (> 60 years) unfit for intensive chemotherapy with cytarabine and anthracyclines are also eligible to this trial given that no clinically beneficial therapy exists for these patients
  • Patients with secondary AML or therapy related disease (t-AML) are eligible; patients who received decitabine or 5-azacytidine as prior treatment for myelodysplastic syndrome (MDS) or AML remain eligible; however, none of these agents is permitted within 6 months of study entry
  • If the patient has co-morbid medical illness, life expectancy attributed to this must be greater than 6 months
  • Eastern Cooperative Oncology Group (ECOG) performance status < 2
  • Total bilirubin < 2.0 mg/dL
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  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2.5 X institutional upper limit of normal
  • Creatinine < 2.0 mg/d
  • Glomerular filtration rate (GFR) > 50 mL/min
  • New York Heart Association (NYHA) congestive heart failure (CHF) class II or better
  • Female patients of child-bearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at screening, and male patients must use an effective barrier method of contraception if sexually active with a female of child]bearing potential; acceptable methods of contraception are condoms with contraceptive foam, oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal; for both male and female patients, effective methods of contraception must be used throughout the study and for three months following the last dose
  • Ability to understand and willingness to sign the written informed consent document
  • Human immunodeficiency virus (HIV) infection without history of acquired immune deficiency syndrome (AIDS) and sufficiently high cluster of differentiation (CD)4 cells (> 400/mm^3) and low HIV viral loads (< 30,000 copies/ml plasma) not requiring anti-HIV therapy are eligible
  • Patients must have recovered from the toxicity of prior therapy to less than grade 2

Who cannot join

  • Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
  • Patients receiving any other investigational agents or patients that have received other investigational agents within 14 days of enrollment
  • Patients with active central nervous system (CNS) malignancy; asymptomatic small lesions are not considered active; treated lesions may be considered inactive if they are stable for at least 3 months; patients with malignant cells in their cerebrospinal fluid (CSF) without CNS symptoms may be included
  • Patients with history of allergic reactions attributed to compounds of similar chemical or biologic composition to decitabine that are not easily managed
  • Major surgery within 2 weeks before day 1
  • Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose
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  • Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C virus (HCV) ribonucleic acid (RNA) or HBsAg (hepatitis B virus [HBV] surface antigen)
  • Patients with significantly diseased or obstructed gastrointestinal tract or uncontrolled vomiting or diarrhea
  • History of seizures, movement disorders or cerebrovascular accident within the past 3 years prior to cycle 1 day 1
  • Patients with macular degeneration, uncontrolled glaucoma, or markedly decreased visual acuity
  • Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure (New York Heart Association [NYHA] class III or IV), unstable angina pectoris, myocardial infarction within 6 months prior to enrollment, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
  • Patients with serious medical or psychiatric illness likely to interfere with participation in this clinical study
  • Pregnant women or women who are breastfeeding are excluded from this study; confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening; pregnancy testing is not required for post-menopausal or surgically sterilized women
  • Patients with advanced malignant solid tumors are excluded
  • Patients with renal failure (GFR < 50 mL/min) are excluded
  • Patients that in the opinion of the investigators are significantly below their ideal body weight

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

    Columbus, Ohio, 43210

Other trials in United States

About this study

Official title: Phase I Study of Decitabine (Dacogen) and Selinexor (KPT-330) in Acute Myeloid Leukemia

This phase I trial studies the side effects and best dose of Selinexor when given together with decitabine in treating patients with acute myeloid leukemia that has returned after treatment (relapsed) or does not respond to treatment (refractory). Drugs used in chemotherapy, such as decitabine and Selinexor, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate the safety and tolerability of Selinexor (KPT-330) in combination with decitabine in patients with acute myeloid leukemia (AML).

II. To define the specific toxicities, maximum tolerated dose (MTD) and the dose limiting toxicity (DLT) of this combination.

III. To determine the Recommended Phase 2 Dose (RP2D) of this combination.

SECONDARY OBJECTIVES:

  1. To determine the overall response rate (ORR). II. To determine the rate and duration of complete remission (CR) +/- hematological recovery of KPT-330 plus decitabine in AML.

III. To conduct pharmacodynamic studies by measuring the effect of this chemotherapy combination on the kinome, micronome and epigenome.

OUTLINE: This is a dose-escalation study of selinexor.

INDUCTION: Patients receive decitabine intravenously (IV) over 1 hour on days 1-10 and Selinexor orally (PO) on days 11, 13, 18, 20, 25 and 27. Treatment repeats every 31 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients receive decitabine IV over 1 hour on days 1-5 and Selinexor PO on days 6, 8, 13, 15, 20 and 22. Courses repeat every 31 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Being tested
decitabine, selinexor, pharmacological study, laboratory biomarker analysis
Keywords
AML, Acute Myeloid Leukemia, Adult Acute Myeloid Leukemia with T(8;21)(Q22;Q22), adult Acute Myeloid Leukemia with 11q23 (MLL) abnormalities, adult Acute Myeloid Leukemia with del(5q), adult Acute Myeloid Leukemia with inv(16)(p13;q22)
Medical subject headings
Leukemia, Myeloid, Acute, Congenital Abnormalities

What participants receive

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

  • decitabineDrug

    Also called 5-aza-dCyd, 5AZA, DAC

    Given IV

  • selinexorDrug

    Also called CRM1 nuclear export inhibitor KPT-330, KPT-330, selective inhibitor of nuclear export KPT-330, SINE KPT-330

    Given PO

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT02093403
Study groupRoleWhat they receive
Treatment (decitabine and selinexor)ExperimentalINDUCTION: Patients receive decitabine IV over 1 hour on days 1-10 and selinexor PO on days 11, 13, 18, 20, 25 and 27. Treatment repeats every 31 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive decitabine IV over 1 hour on days 1-5 and selinexor PO on days 6, 8, 13, 15, 20 and 22. Courses repeat every 31 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: decitabine; Drug: selinexor; Other: pharmacological study; Other: laboratory biomarker analysis

What is being measured

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

  1. MTD defined as the dose where at most one patient experiences DLT with the next higher dose having at least 2 patients who experience DLT graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03

    Measured: 31 days

  2. Incidence of severe (grade 3+) adverse events or toxicities assessed by NCI CTCAE version 4.03

    The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.

    Measured: Up to 3 years

  3. Tolerability of the regimen defined by the number of patients who required dose modifications and/or dose delays

    Measured: Up to 3 years

  4. Proportion of patients who go off treatment due to adverse reactions

    Measured: Up to 3 years

Secondary outcomes (6)

  1. Overall response rate

    Responses will be summarized by simple descriptive summary statistics across all dose levels. Overall response rate will estimated at the MTD and defined as the number of patients who achieve any level of clinical response (e.g. CR, incomplete blood count recovery, morphologic CR) divided by the total number of evaluable patients (i.e. any patient who received at least one dose of study treatment).

    Measured: Up to 3 years

  2. Complete response rate

    Responses will be summarized by simple descriptive summary statistics across all dose levels. Complete response rate will be estimated in those patients treated at the MTD.

    Measured: Up to 3 years

  3. Change in expression of XPO1

    Changes in expression of these markers across time will be explored by dose level graphically. Relationships between baseline expression levels and changes in expression levels with response and certain toxicities will also be explored graphically (e.g. side-by-side boxplots) and with quantitative summaries. Confidence intervals will be presented as the primary method of analysis. Correlations among expression of the genes, micro-ribonucleic acids (miRs), and methylated signatures will be evaluated using scatterplots and the Spearman-rank correlation coefficient.

    Measured: Baseline to up to day 31 of course 1

  4. Change in expression of genes associated with XPO1

    Changes in expression of these markers across time will be explored by dose level graphically. Relationships between baseline expression levels and changes in expression levels with response and certain toxicities will also be explored graphically (e.g. side-by-side boxplots) and with quantitative summaries. Confidence intervals will be presented as the primary method of analysis. Correlations among expression of the genes, miRs, and methylated signatures will be evaluated using scatterplots and the Spearman-rank correlation coefficient.

    Measured: Baseline to up to day 31 of course 1

  5. Change in expression of miRs associated with XPO1

    Changes in expression of these markers across time will be explored by dose level graphically. Relationships between baseline expression levels and changes in expression levels with response and certain toxicities will also be explored graphically (e.g. side-by-side boxplots) and with quantitative summaries. Confidence intervals will be presented as the primary method of analysis. Correlations among expression of the genes, miRs, and methylated signatures will be evaluated using scatterplots and the Spearman-rank correlation coefficient.

    Measured: Baseline to up to day 31 of course 1

  6. Change in expression of methylated signatures

    Changes in expression of these markers across time will be explored by dose level graphically. Relationships between baseline expression levels and changes in expression levels with response and certain toxicities will also be explored graphically (e.g. side-by-side boxplots) and with quantitative summaries. Confidence intervals will be presented as the primary method of analysis. Correlations among expression of the genes, miRs, and methylated signatures will be evaluated using scatterplots and the Spearman-rank correlation coefficient.

    Measured: Baseline to up to day 31 of course 1

Timeline

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

  1. First posted21 Mar 2014 (estimated)
  2. Study startMar 2014
  3. Primary completion26 Nov 2016
  4. Study completion26 Nov 2016

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02093403
Sponsor's protocol ID
OSU-13182
Other IDs
NCI-2014-00559
Status last verified
Dec 2017
First submitted
19 Mar 2014
Last updated
8 Dec 2017
Results posted
No
Data monitoring committee
Yes

Publications

  • Bhatnagar B, Zhao Q, Mims AS, Vasu S, Behbehani GK, Larkin K, Blachly JS, Blum W, Klisovic RB, Ruppert AS, Orwick S, Oakes C, Ranganathan P, Byrd JC, Walker AR, Garzon R. Selinexor in combination with decitabine in patients with acute myeloid leukemia: results from a phase 1 study. Leuk Lymphoma. 2020 Feb;61(2):387-396. doi: 10.1080/10428194.2019.1665664. Epub 2019 Sep 23.

    PubMed 31545113

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing decitabine, selinexor and pharmacological study in people with Acute Myeloid Leukemia and Secondary Acute Myeloid Leukemia, run by Bhavana Bhatnagar 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 14 inclusion and 16 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 Dec 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 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.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

MTD defined as the dose where at most one patient experiences DLT with the next higher dose having at least 2 patients who experience DLT graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (time frame: 31 days). The study lists 4 primary outcomes in all. 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 NCT02093403, which also lists 1 linked publication.

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 Dec 2017.

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