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CD30-positive LymphomaPhase 1AD3LENCT02780011

Alsertib (MLN8237) and Brentuximab Vedotin for Relapsed/Refractory CD30-Positive Lymphomas and Solid Malignancies

A Phase 1 study testing Brentuximab Vedotin and Alsertib in people with CD30-positive Lymphoma and CD30-positive Solid Tumor, run by Eric Bernicker, MD at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This is an open label phase I trial designed to evaluate the maximum tolerated dose, dose-limiting toxicities, pharmacokinetics, and activity of the combination of alsertib (MLN8237) and brentuximab vedotin in patients with relapsed/refractory CD30-positive lymphomas and solid malignancies. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Brentuximab Vedotin and Alsertib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
Dec 2015to Sep 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

  • Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care;
  • Relapsed or refractory CD30-positive lymphoma such as Hodgkin's and anaplastic large cell lymphoma or CD30-positive cancer such as testicular embryonal carcinoma, cutaneous angiosarcoma, and nasopharyngeal non-keratinizing carcinoma or any CD30-positive solid tumor. CD30 positivity is defined as ≥ 25% CD30 expression by immunohistochemistry. (CD30 analysis will be performed by an in-house CLIA and CAP-accredited laboratory);
  • Male or female patients aged ≥ 18 years;
  • Adequate cardiac function (cardiac ejection fraction of ≥ 45%);
  • Patients must have received at least two prior therapies for CD30-positive lymphoma or solid malignancy;
  • Absolute neutrophil count > 1500/mm³, platelets > 100,000/mm³, and hemoglobin > 8 g/dL. Values must be obtained without the need for myeloid growth factor or platelet transfusion support within 14 days of the first dose of the study treatment; however, erythrocyte growth factor is allowed as per the American Society of Clinical Oncology guidelines;
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  • Total bilirubin ≤ 1.5 x upper limit of normal (ULN) and aspartate transaminase (AST) and alanine transaminase (ALT) < 2.5 x ULN. AST and/or ALT may be up to 5 x ULN if liver metastases are present;
  • Adequate renal function as defined by a serum creatinine of < 2.0 mg/dL and calculated creatinine clearance of ≥ 30 mL/minute;
  • Eastern Cooperative Oncology Group performance status of 0 to 2;
  • Female patients must be either:
  • post-menopausal for at least one year before the screening visit, or
  • surgically sterilized, or
  • willing to use an acceptable method of birth control (i.e., hormonal contraceptive, intrauterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study;
  • Male patients, even if surgically sterilized (i.e., post-vasectomy status), must agree to use an acceptable contraceptive method during the course of the study and for 4 months after the last dose of alisertib.

Who cannot join

  • Radiation therapy to more than 25% of the bone marrow. Whole pelvic radiation is considered to be over 25%;
  • Prior allogeneic bone marrow or organ transplantation;
  • Expected survival of less than 4 weeks;
  • Known gastrointestinal (GI) disease or GI procedures that could interfere with the oral absorption of or tolerance to alisertib. Examples include but are not limited to partial gastrectomy, history of small intestine surgery, and celiac disease;
  • Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease;
  • Known cerebral or meningeal disease (Hodgkin's lymphoma or any other etiology), including signs or symptoms of progressive multifocal leukoencephalopathy;
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  • Symptomatic neurologic disease that compromises normal activities of daily living or requires medication;
  • Requirement for constant or intermittent administration of a proton pump inhibitor, a H2 antagonist, or pancreatic enzymes. Intermittent use of antacids or H2 antagonists is allowed;
  • Systemic infection requiring intravenous antibiotic therapy within 14 days preceding the first dose of the study treatment or other severe viral or bacterial infection;
  • Absolute QT interval of > 460 msec in the presence of > 4.0 mEq/L potassium and > 1.8 mg/dL magnesium;
  • Myocardial infarction within 6 months prior to enrollment or has New York Heart Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any electrocardiogram abnormality at screening has to be documented by the investigator as not medically relevant;
  • Female patient who is pregnant or breastfeeding. Confirmation that the subject is not pregnant must be established by a negative serum beta human chorionic gonadotropin pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women;
  • Patient has received other investigational drugs within 14 days of enrollment;
  • Serious medical or psychiatric illness likely to interfere with participation in this clinical study;
  • Other severe acute or chronic medical or psychiatric condition, including uncontrolled diabetes, malabsorption, resection of the pancreas or upper small bowel, requirement for pancreatic enzymes, any condition that would modify small bowel absorption of oral medications, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for enrollment in this study;
  • Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy;
  • Treatment with clinically significant enzyme inducers, such as phenytoin, carbamazepine, phenobarbital, rifampin, rifabutin, rifapentine, and St. John's wort, within 14 days prior to the first dose of alisertib;
  • Known history of human immunodeficiency virus, hepatitis B, or hepatitis C infection. Testing is not required in the absence of clinical findings or suspicion;
  • Prior administration of an Aurora A kinase-targeted agent, including alisertib;
  • Prior administration of brentuximab vedotin is allowed only if the patient did not experience disease progression while on treatment;
  • Known hypersensitivity to recombinant proteins, murine proteins, or any excipient contained in the drug formulation of brentuximab vedotin;
  • Concurrent or recent (within 2 weeks) use of strong cytochrome P450 (CYP) 3A4 inhibitors such as ketoconazole, itraconazole, clarithromycin, atanazir, inddinavir, nefazodone, neflinavir, ritonavir, saquinavir, telithromycin, and voriconazole;
  • Concurrent or recent (within 2 weeks) use of potent CYP3A4 inducers such as dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, and St. John's wort;
  • Concurrent or recent (within 2 weeks) use of a P-glycoprotein inhibitor such as cyclosporine, ketoconazole, ritonavir, saquinavir, tacrolimus, or verapamil;
  • Receipt of corticosteroids within 7 days prior to the first dose of the study treatment, unless the patient has been taking a continuous dose of no more than 15 mg/day of prednisone for at least 1 month prior to the first dose of the study treatment. Low-dose steroid use for the control of nausea and vomiting will be allowed. Topical steroid use is permitted. Inhaled steroids are permitted;
  • Inability to swallow oral medication or inability or unwillingness to comply with the administration requirements related to alisertib;
  • Administration of myeloid growth factors or platelet transfusion within 14 days prior to the first dose of the study treatment.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Houston Methodist Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: A Phase I Study of the Combination of Alsertib (MLN8237) and Brentuximab Vedotin in Relapsed/Refractory CD30-Positive Lymphomas and Solid Malignancies

This is an open label phase I trial designed to evaluate the maximum tolerated dose, dose-limiting toxicities, pharmacokinetics, and activity of the combination of alsertib (MLN8237) and brentuximab vedotin in patients with relapsed/refractory CD30-positive lymphomas and solid malignancies. Cohorts of 3-6 patients will receive escalating or de-escalating doses of MLN8237 based on a 3 + 3 design.

Read the detailed description

This is an investigator-initiated, open label phase I trial designed to evaluate the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics, and activity of brentuximab vedotin in combination with MLN8237 in patients with relapsed/refractory CD30-positive lymphomas and solid malignancies.

Brentuximab vedotin at a fixed dose of 1.8 mg/kg will be administered on Day 1 every three weeks as a 30-minute outpatient intravenous infusion. MLN8237 will be orally administered in two divided doses from Days 1-7. The starting dose (level 0) of MLN8237 will be 60 mg daily given in two divided doses (30 mg qAM, 30 mg qPM).The dose of MLN8237 will be escalated in 20-mg increments up to 100 mg daily and de-escalated in 20-mg decrements to 40 mg daily. The fixed dose of brentuximab vedotin on Day 1 and daily dose of MLN8237 on Day 1-7 will constitute one treatment cycle. If no DLTs are observed in the last study cohort, the cohort will be expanded to include a total of 12 patients. If a de-escalation dose is required because 2 or more patients experience DLTs, the next lower cohort will be studied. If 2 or more patients do not experience DLTs, this dose will be declared the MTD. This cohort will be expanded to include 12 patients in order to study the biological endpoints and clinical benefit of the combination. If at any point during the expansion cohort phase of the trial 33% or more of the patients treated at the MTD/maximum administered dose experience a DLT, accrual of additional patients at this does level will cease and the next lowest dose may be explored.

Being tested
Brentuximab Vedotin, Alsertib
Keywords
CD30+, Relapsed, Refractory, ALCL
Medical subject headings
Recurrence

What participants receive

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

  • Brentuximab VedotinDrug

    Also called Adcetris

    Antibody-drug conjugate composed of the anti-CD30 chimeric immunoglobulin G1 monoclonal antibody cAC10 and the antimicrotubule drug monomethyl auristatin E connected by a protease-cleavable linker.

  • AlsertibDrug

    Also called MLN8237

    Aurora A kinase inhibitor

Study groups in NCT02780011
Study groupRoleWhat they receive
Alsertib and Brentuximab VedotinExperimentalBrentuximab vedotin at a fixed dose of 1.8 mg/kg will be administered by intravenous infusion on day 1 of every 21-day cycle. MLN8237 at a dose of 60 mg will be orally administered daily in 2 divided doses (30 mg qAM, 30 mg qPM) from days 1 to 7 of each 21-day cycle. MLN8237 dose will be escalated in 20-mg increments to the maximum dose of 100 mg (Level 2) or de-escalated in a 20-mg decrement to the minimum dose of 40 mg (Level -1).
Receives: Drug: Brentuximab Vedotin; Drug: Alsertib

What is being measured

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

  1. Maximum tolerated dose (MTD)

    Determine the MTD of the alsertib (MLN8237) and brentuximab vedotin combination in patients with relapsed/refractory CD30-positive lymphomas and solid malignancies.

    Measured: Approximately 12 weeks

Secondary outcomes (4)
  1. Dose-limiting toxicities (DLTs)

    Describe the DLTs and other toxicities associated with the alsertib (MLN8237) and brentuximab vedotin combination as assessed by CTCAE v4.0.

    Measured: Approximately 12 weeks

  2. Recommended phase 2 dose (RP2D)

    Determine the RP2D of the alsertib (MLN8237) and brentuximab vedotin combination.

    Measured: Approximately 12 weeks

  3. Antitumor activity

    Document the antitumor activity of the alsertib (MLN8237) and brentuximab vedotin combination as assessed by modified IWG criteria and RECIST 1.1.

    Measured: Approximately 12 weeks

  4. Area under the plasma concentration versus time curve

    Determine the area under the plasma concentration versus time curve of alsertib (MLN8237) and brentuximab vedotin.

    Measured: Cycle 1, Day 1 at pre-infusion and 10 min, 24 h, and 48 h post-infusion; trough sample on Cycle 1, Day 8; and Cycle 2, Day 1 at pre-infusion and 12 h and 24 h post-infusion.

Timeline

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

  1. First posted23 May 2016 (estimated)
  2. Study startDec 2015
  3. Primary completionSep 2018 (estimated)
  4. Study completionSep 2018 (estimated)

Why it stopped: lack of funding

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
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02780011
Sponsor's protocol ID
Pro00012815
Acronym
AD3LE
Status last verified
Jul 2018
First submitted
24 Feb 2016
Last updated
27 Jul 2018
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Yes: Data and materials on human subjects will be shared with other eligible investigators through appropriate means in accordance with the NIH policy on Sharing Research Data (NIH Guide, February 26, 2003). Data will be also shared with the funding agency and regulatory agencies as required. Data will be shared with other investigators within the limits of HIPAA and other patient confidentiality requirements. This will generally require removal of all patient identifiers for all source documents and the use of arbitrarily assigned one-way identifiers. In some cases, requestors will be asked to sign a formal data sharing agreement that will provide for a commitment to use data only for research purposes and not to identify individuals, keep the data secure, and destroy or return data after analyses are complete. Prior approval will be obtained from collaborating investigators, research sponsors, and/or other stake-holders before sharing if proprietary information or products are involved.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Brentuximab Vedotin and Alsertib in people with CD30-positive Lymphoma and CD30-positive Solid Tumor, run by Eric Bernicker, MD 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 27 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: withdrawn, as of the sponsor's last update on 27 Jul 2018. 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 was withdrawn before enrolling participants, so there are no results.

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) (time frame: Approximately 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 27 Jul 2018.

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