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

NCT02875002 | Withdrawn Phase 1

• 1 other identifier: 1601017105
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

Brief 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. A standard 3+3 dose-escalation design will be employed with study enrollment beginning at dose level 1.

Conditions

Relapsed and Refractory Aggressive B- and T-cell Lymphomas; Lymphoma

Outcome Measures

Primary Outcomes (2)

• 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.

  up to 2 years

• Adverse Events

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

  up to 2 years

Study Arms (1)

All subjects

EXPERIMENTAL

Subjects have relapsed and refractory aggressive B- and T-cell lymphomas and will receive both Belinostat and Volasertib.

Drug: volasertib; Drug: belinostat

Interventions

volasertib DRUG

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.

All subjects

belinostat DRUG

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.

All subjects

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Yale University: lead
• Massey Cancer Center: collaborator
• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: collaborator

Study Sites (3)

Yale Cancer Center

New Haven, Connecticut, 06511, United States

Location

Sidney Kimmel Comprehensive Cancer

Baltimore, Maryland, 21287, United States

Location

Massey Cancer Center

Richmond, Virginia, 23298, United States

Location

MeSH Terms

Conditions

Recurrence; Lymphoma, T-Cell; Lymphoma

Interventions

BI 6727; belinostat

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Steven Gore, MD

  Yale University

  PRINCIPAL INVESTIGATOR

• Iris Isufi, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2016
• First Posted: August 22, 2016
• Study Start: October 1, 2016
• Primary Completion: March 1, 2018
• Study Completion: September 1, 2018
• Last Updated: December 22, 2017

Record last verified: 2017-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)