Relapsed and Refractory Aggressive B- and T-cell Lymphomas, Lymphoma
Conditions
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.
Interventions
DRUGvolasertib
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.
DRUGbelinostat
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.
Sponsors
Massey Cancer Center
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Yale University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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 * 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
Exclusion criteria
A patient who meets any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Doses (MTD) | up to 2 years | 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. |
| Adverse Events | up to 2 years | To evaluate the safety and toxicity of volasertib and belinostat when given in combination |
Countries
United States
Outcome results
None listed