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Adult B Acute Lymphoblastic LeukemiaPhase 1NCT01567709

Alisertib in Combination With Vorinostat in Treating Patients With Relapsed or Recurrent Hodgkin Lymphoma, B-Cell Non-Hodgkin Lymphoma, or Peripheral T-Cell Lymphoma

A Phase 1 study testing Alisertib, Laboratory Biomarker Analysis and Pharmacological Study in people with Adult B Acute Lymphoblastic Leukemia and Adult T Acute Lymphoblastic Leukemia, run by National Cancer Institute (NCI) at 5 sites 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 the best dose of alisertib when given together with vorinostat in treating patients with Hodgkin lymphoma, B-cell non-Hodgkin lymphoma, or peripheral T-cell lymphoma that has come back. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Alisertib, Laboratory Biomarker Analysis and Pharmacological Study
Could I receive a placebo?
No, everyone receives an active treatment
How many people
34 participants
Where
5 sitesUnited States
Study dates
16 Apr 2012to 29 Mar 2018
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have a histologically or cytologically confirmed lymphoid malignancy (like Hodgkin lymphoma or one of the mature B- or T-cell non-Hodgkin lymphomas as classified by World Health Organization [WHO]) for which standard curative or palliative measures do not exist or are no longer effective
  • Patients must have measurable disease in two dimensions and >= 2 cm is acceptable (or 1.5 cm if 0.5 slices are used, as in spiral computed tomography [CT] scans); lesions that are considered intrinsically non-measurable include the following:
  • Bone lesions
  • Leptomeningeal disease
  • Ascites
  • Pleural/pericardial effusion
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  • Inflammatory breast disease
  • Lymphangitis cutis/pulmonis
  • Abdominal masses that are not confirmed and followed by imaging techniques
  • Cystic lesions
  • Lesions that are situated in a previously irradiated area
  • Patients must have had at least 1 prior systemic chemotherapy (not just steroids or local radiation); last chemotherapy or radiation must be at least 4 weeks prior to enrollment on this study; patients who decline other potentially curative therapy may be eligible; prior radiation therapy must not have been to more than 25% of the bone marrow; whole pelvic radiation is considered to be over 25%
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Life expectancy of greater than 12 weeks
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total/direct bilirubin < 1.5 X institutional upper limit of normal; patients with elevation of indirect (unconjugated) bilirubin alone, as in Gilbert's syndrome, are eligible
  • 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 =< institutional upper limit of normal OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Prior allogeneic stem cell transplant patients will be allowed to enroll if they are past day +100 of transplant, have no active graft-versus-host-disease, are not on any immunosuppressants and have been off immunosuppressants for at least 4 weeks; prior autologous stem cell transplant patients will also be allowed to enter this study if they are past their day +100 of transplant
  • 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, for the duration of study participation, and 4 months after completion of MLN8237 administration; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of MLN8237 administration
  • Ability to understand and the willingness to sign a written informed consent document
  • According to current guidelines, patients must be able to take oral medication and to maintain a fast as required for 2 hours before and 1 hour after MLN8237 administration; these guidelines may change pending results from an ongoing food effects study

Who cannot join

  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Patients who are receiving any other investigational agents
  • Patients with known brain metastases should be excluded from this clinical trial
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to MLN8237, including but not limited to established allergic reaction to benzodiazepines
  • Treatment with valproic acid within 14 days prior to initiation of study and during the study
  • Prior use of valproic acid or any other histone deacetylase (HDAC) inhibitor for lymphoma treatment
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  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, 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 MLN8237
  • Human Immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
  • Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen; or any conditions that could result in excessive toxicity associated with the benzodiazepine-like effects of MLN8237
  • Requirement for constant administration of proton pump inhibitor, histamine (H2) antagonist, or pancreatic enzymes; intermittent uses of antacids or H2 antagonists are allowed
  • Inability to swallow oral medication or to maintain a fast as required for 2 hours before and 1 hour after MLN8237 administration or any condition that would modify small bowel absorption of oral medications, including malabsorption, or resection of pancreas or upper bowel
  • Treatment with clinically significant enzyme inducers, such as the enzyme-inducing antiepileptic drugs phenytoin, carbamazepine, oxcarbazepine, primidone or phenobarbital, or rifampin, rifabutin, rifapentine, or St. John's wort within 14 days prior to the first dose of MLN8237 and during the study
  • Patients with New York Heart Association (NYHA) class II-IV heart failure

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

  • Penn State Milton S Hershey Medical Center

    Hershey, Pennsylvania, 17033-0850

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • University of Pittsburgh Cancer Institute (UPCI)

    Pittsburgh, Pennsylvania, 15232

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

Other trials in United States

About this study

Official title: Phase I Study of the Aurora Kinase a Inhibitor MLN8237 in Combination With the Histone Deacetylase Inhibitor Vorinostat in Lymphoid Malignancies

This phase I trial studies the side effects and the best dose of alisertib when given together with vorinostat in treating patients with Hodgkin lymphoma, B-cell non-Hodgkin lymphoma, or peripheral T-cell lymphoma that has come back. Alisertib and vorinostat 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 MLN8237 (alisertib) when given in combination with vorinostat and to select a dose and schedule for further testing (recommended Phase 2 dose: RP2D) in patients with lymphoid malignancies.

II. To describe the toxicities of MLN8237 when given in combination with vorinostat on a 21-day schedule.

III. To determine any clinical responses with MLN8237 in combination with vorinostat.

IV. To compare the plasma pharmacokinetics of MLN8237 when given alone and in combination with vorinostat.

  1. To perform immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) analysis to determine aurora kinase A (AURKA) expression in archival formalin-fixed paraffin-embedded sections from the most recent available tumor specimens of patients.

VI. To perform correlative studies for apoptosis and proliferation on bone marrow and lymph node specimens, where available, obtained from patients in the expanded cohort at RP2D.

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

Patients receive alisertib orally (PO) twice daily (BID) on days 1-7 or days 1-3 and 8-10, and vorinostat PO BID on days 1-14 or days 1-5 and 8-12. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

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

Being tested
Alisertib, Laboratory Biomarker Analysis, Pharmacological Study, Vorinostat
Medical subject headings
Burkitt Lymphoma, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Lymphoma, Large-Cell, Anaplastic, Immunoblastic Lymphadenopathy, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, B-Cell, Marginal Zone, Intraocular Lymphoma, Lymphoma, T-Cell

What participants receive

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

  • AlisertibDrug

    Also called Aurora A Kinase Inhibitor MLN8237, MLN-8237, MLN8237

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacological StudyOther

    Correlative studies

  • VorinostatDrug

    Also called L-001079038, MSK-390, SAHA, Suberanilohydroxamic Acid

    Given PO

Study groups in NCT01567709
Study groupRoleWhat they receive
Treatment (alisertib, vorinostat)ExperimentalPatients receive alisertib PO BID on days 1-7 or days 1-3 and 8-10, and vorinostat PO BID on days 1-14 or days 1-5 and 8-12. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Alisertib; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Vorinostat

What is being measured

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

  1. MTD of alisertib defined as the highest dose tested in which less than 33% of patients experienced dose-limiting toxicity (DLT) graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v.)4.0

    The toxicities observed at each dose level will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by NCI CTCAE version 4.0) and nadir or maximum values for the laboratory measures, time of onset (i.e. course number), duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects by dose and by course.

    Measured: 21 days

Secondary outcomes (2)

  1. Incidence of toxicities produced by alisertib in combination with vorinostat assessed by the NCI CTCAE version 4.0

    The toxicities observed at each dose level will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by NCI CTCAE version 4.0) and nadir or maximum values for the laboratory measures, time of onset (i.e. course number), duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects by dose and by course.

    Measured: Up to 2 years

  2. Clinical response rate

    Summarized by exact binomial confidence intervals.

    Measured: Up to 2 years

Timeline

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

  1. First posted30 Mar 2012 (estimated)
  2. Study start16 Apr 2012
  3. Primary completion29 Mar 2018
  4. Study completion29 Mar 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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
34 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01567709
Sponsor's protocol ID
NCI-2012-00715
Other IDs
NCI-2012-00715, NCI#9091, PHI-67, CDR0000729769, CHNMC-PHI-67, PHI-67, 9091, P30CA033572
Status last verified
Apr 2018
First submitted
29 Mar 2012
Last updated
11 Apr 2018
Results posted
No

Publications

  • Siddiqi T, Frankel P, Beumer JH, Kiesel BF, Christner S, Ruel C, Song JY, Chen R, Kelly KR, Ailawadhi S, Kaesberg P, Popplewell L, Puverel S, Piekarz R, Forman SJ, Newman EM. Phase 1 study of the Aurora kinase A inhibitor alisertib (MLN8237) combined with the histone deacetylase inhibitor vorinostat in lymphoid malignancies. Leuk Lymphoma. 2020 Feb;61(2):309-317. doi: 10.1080/10428194.2019.1672052. Epub 2019 Oct 16.

    PubMed 31617432

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Alisertib, Laboratory Biomarker Analysis and Pharmacological Study in people with Adult B Acute Lymphoblastic Leukemia and Adult T Acute Lymphoblastic Leukemia, run by National Cancer Institute (NCI) at 5 sites 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 23 inclusion and 14 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 11 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites 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 of alisertib defined as the highest dose tested in which less than 33% of patients experienced dose-limiting toxicity (DLT) graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v.)4.0 (time frame: 21 days). 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 NCT01567709, 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 11 Apr 2018.

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