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Relapsed and Refractory Aggressive B- and T-cell LymphomasPhase 1NCT02875002

Study of Volasertib and Belinostat in Patients With Relapsed and Refractory Aggressive B-cell and T-cell Lymphomas

A Phase 1 study testing volasertib and belinostat in people with Relapsed and Refractory Aggressive B- and T-cell Lymphomas and Lymphoma, run by Yale University at 3 sites in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This phase 1, multicenter, open-label study is designed to find the RP2D of volasertib, a PLK1 inhibitor, and belinostat, an HDAC inhibitor, when given in combination to patients with relapsed or refractory B-cell or T-cell lymphoma. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
volasertib and belinostat
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
3 sitesUnited States
Study dates
Oct 2016to 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

  • A patient must meet all of the following inclusion criteria to be eligible to participate in the study.
  • Histologically confirmed aggressive B-cell or T-cell lymphoma including the following:
  • B-cell lymphomas
  • DLBCL (including transformed follicular lymphoma)
  • Mantle cell lymphoma
  • Burkitt lymphoma
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  • Peripheral T-cell lymphoma (PTCL) excluding cutaneous T-cell lymphoma
  • Disease that is relapsed or refractory after a minimum of 2 previous therapies, if B-cell lymphoma, or a minimum of 1 previous therapy, if PTCL
  • For patients who have had autologous stem cell transplant, disease relapse must be more than 100 days following transplant.
  • For patients who have had allogeneic stem cell transplant, all of the following conditions must be met:
  • ≥ 6 months since allogeneic transplant
  • Graft vs. host disease (GVHD) is not present
  • Patient is not currently on immunosuppressive therapy
  • At least one site of measurable disease by PET/CT: a node measurable in 2 diameters and with longest diameter >1.5cm or an extranodal lesion measurable in 2 diameters and with longest diameter >1cm.
  • Age ≥ 18 years of age
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (see Appendix 1)
  • Life expectancy of at least 3 months
  • CBC with differential providing evidence of adequate bone marrow function as defined below:
  • Absolute neutrophil count (ANC) ≥ 1500/mm3 without growth factor support for 7 days
  • Platelets ≥ 75,000/mm3 (without transfusion for 7 days)
  • Adequate renal function defined as: Creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated or actual creatinine clearance ≥ 60 mL/min (see Appendix 2 for the Cockcroft -Gault Formula to calculate creatinine clearance)
  • Adequate hepatic function as defined below:
  • AST ≤ 2.5 x ULN
  • ALT ≤ 2.5 x ULN
  • Total bilirubin ≤ 1.5 mg/dL
  • Note: Patients with documented Gilbert's syndrome are eligible if total bilirubin is ≤ 3.0 mg/dL.
  • Serum potassium and serum magnesium within normal limits Note: Electrolytes may be corrected with supplementation.
  • For a woman of childbearing potential (WCBP), a negative serum pregnancy test performed within 14 days prior to study enrollment (7 days prior to initiation of study treatment) Note: WCBP is defined as any woman who has not had a hysterectomy or bilateral oophorectomy and is not postmenopausal (i.e., she has had menses in the preceding 24 consecutive months)
  • WCBP and male patients must agree to use a highly effective method of birth control for the duration of study treatment and for 6 months following completion of study treatment Note: A highly effective method of contraception is defined as one that results in a low failure rate (i.e. less than 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence or vasectomised partner.
  • Ability to understand and willingness to sign a written informed consent document

Who cannot join

  • A patient who meets any of the following exclusion criteria is ineligible to participate in the study.
  • Any investigational treatment within 30 days prior to initiation of study treatment
  • Plans for concurrent treatment with other investigational agents
  • Plans for other concurrent cancer treatment including steroids for cancer control
  • Chemotherapy or large field radiotherapy within 3 weeks prior to initiation of study treatment
  • Previous histone deacetylase inhibitor administered as cancer treatment.
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  • History of brain metastasis including leptomeningeal metastasis
  • QTc interval ≥450 (i.e., ≥ grade 0, per CTCAE version 4) on ECG prior to initiation of study treatment. If baseline QTc on screening ECG is ≥ 450 ms (i.e., ≥ grade 1)
  • Check potassium and magnesium serum levels
  • Correct any identified hypokalemia and/or hypomagnesemia and repeat ECG to confirm QTc interval
  • For patients with baseline HR < 60 or > 100 bpm, manual read of QT by cardiologist is required, with Fridericia correction applied to determine the QTcF interval.
  • Note: For patients with HR 60-100 bpm, no manual read of QTc is required.
  • Any of the following related to risk of torsades de pointes and sudden cardiac death:
  • History of sustained ventricular tachycardia (VT, ventricular fibrillation (VF), torsades de pointes, or resuscitated cardiac arrest unless currently addressed with an implanted cardiac defibrillator
  • Concomitant treatment with an anti-arrhythmic agent to prevent or control arrhythmia. Agents used for rate-control of atrial fibrillation are permitted provide that they are not prohibited due to potential drug interactions (see Section 6.4)
  • Known congenital long QT syndrome
  • Second degree atrioventricular (AV) block type II, third degree AV block, or ventricular rate < 50 bpm
  • Any of the following related to ischemic heart disease:
  • Angina with ordinary physical activity
  • Note: If angina only occurs with strenuous, rapid, or prolonged exertion, the patient is eligible.
  • Myocardial infarction within 6 months prior to study enrollment
  • Note: If myocardial infarction occurred within 6-12 months prior to study enrollment, patient must be asymptomatic and have had a negative cardiac risk assessment (e.g., treadmill stress test, nuclear medicine stress test, or stress echocardiogram)
  • ECG with evidence of cardiac ischemia (i.e., ST depression of ≥ 2 mm, measured from isoelectric line to ST segment; T-wave inversion ≥ 4 mm measured from isoelectric line to peak of T-wave)
  • Any of the following related to heart failure:
  • New York Heart Association (NYHA) class II, III or IV congestive heart failure (see Appendix 3) or known left ventricular ejection fraction < 40% by MUGA scan or < 50% by echocardiogram or MRI
  • Known hypertrophic cardiomegaly or restrictive cardiomyopathy
  • Clinically significant infection including active hepatitis B or hepatitis C requiring treatment
  • Known human immunodeficiency virus (HIV) seropositivity nNote: HIV testing is not required
  • History of allergic reactions attributed to compounds similar to the chemical or biologic composition of belinostat or volasertib
  • History of another primary malignancy, excluding non-melanoma skin cancer, cervical carcinoma in situ, and/or other in situ cancers treated by local excision, that has not been in remission for at least 2 years
  • Pregnancy or breastfeeding
  • Medical, psychological, or social condition that, in the opinion of the investigator, may increase the patient's risk, interfere with the patient's participation in the study, or hinder evaluation of study results

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Sidney Kimmel Comprehensive Cancer

    Baltimore, Maryland, 21287

  • Yale Cancer Center

    New Haven, Connecticut, 06511

  • Massey Cancer Center

    Richmond, Virginia, 23298

Other trials in United States

About this study

Official title: Phase 1 Study of Volasertib and Belinostat in Patients With Relapsed and Refractory Aggressive B-cell and T-cell Lymphomas

This phase 1, multicenter, open-label study is designed to find the RP2D of volasertib, a PLK1 inhibitor, and belinostat, an HDAC inhibitor, when given in combination to patients with relapsed or refractory B-cell or T-cell lymphoma. A standard 3+3 dose-escalation design will be employed with study enrollment beginning at dose level 1.

Being tested
volasertib, belinostat
Medical subject headings
Recurrence, Lymphoma, T-Cell, Lymphoma

What participants receive

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

  • volasertibDrug

    Volasertib (BI6727) is a small molecule inhibitor of the polo-like kinase 1 (PLK1) protein. Infusion for 60 minutes. Dosing will start at 25 mg/m^2, is schedule to increase to 100mg/m^2, and be administered on days 1 and 8 of each 28-day cycle.

  • belinostatDrug

    Belinostat is a histone deacetylase inhibitor. Infusion will take 30 minutes. Dosing will start at 600 mg/m^2 , is scheduled to increase to 1000 mg/m^2, and will be administered on days 1,2,3 and 8,9,10 of each 28-day cycle.

Study groups in NCT02875002
Study groupRoleWhat they receive
All subjectsExperimentalSubjects have relapsed and refractory aggressive B- and T-cell lymphomas and will receive both Belinostat and Volasertib.
Receives: Drug: volasertib; Drug: belinostat

What is being measured

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

  1. Maximum Tolerated Doses (MTD)

    Dose escalation will follow the traditional 3+3 plan to determine the MTD and the recommended phase 2 doses (RP2D). The MTD will be defined as that dose level at which ≤ 1/6 patients experience Dose Limited Toxicity (DLT), with ≥ 2/6 experiencing DLT at the next higher dose level.

    If the MTD is not reached at dose level 5, consideration will be given to amending the dose level escalation schema to add an additional dose level.

    Measured: up to 2 years

  2. Adverse Events

    To evaluate the safety and toxicity of volasertib and belinostat when given in combination

    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 posted22 Aug 2016 (estimated)
  2. Study startOct 2016
  3. Primary completionMar 2018 (estimated)
  4. Study completionSep 2018 (estimated)

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
NCT02875002
Sponsor's protocol ID
1601017105
Status last verified
Dec 2017
First submitted
17 Aug 2016
Last updated
22 Dec 2017
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing volasertib and belinostat in people with Relapsed and Refractory Aggressive B- and T-cell Lymphomas and Lymphoma, run by Yale University at 3 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 30 inclusion and 32 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 22 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 3 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 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 Doses (MTD) (time frame: up to 2 years). The study lists 2 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 NCT02875002.

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 22 Dec 2017.

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