Phase 1/2 Study of VIP152, Venetoclax, and Prednisone (VVIP) in Relapsed/Refractory Lymphoid Malignancies
Phase 1/2 Study of VIP152, Venetoclax, and Prednisone (VVIP) in Relapsed/Refractory Lymphoid Malignancies
Background:
Non-Hodgkin lymphomas are blood cancers that can be difficult to treat. They can also return after treatment. Examples include diffuse large B-cell lymphoma (DLBCL) and peripheral T-cell lymphoma (PTCL). More effective treatments are needed for these diseases.
Objective:
To test the safety of a study drug (Enitociclib (VIP152) in combination with other drugs used to treat people with aggressive blood cancers.
Eligibility:
People aged 18 years or older diagnosed with DLBCL, PTCL, or related blood cancers. The cancers must have either not responded to treatment or returned after treatment.
Design:
Participants will undergo screening. They will have a physical exam with scans and blood and urine tests. They will have imaging scans and tests of their heart function. They may also provide a bone marrow aspiration or biopsy.
Participants may provide a saliva sample for deoxyribonucleic acid (DNA) testing.
Participants will receive study treatment in cycles. Each cycle is 21 days.
Participants will take two drugs by mouth at home once a day on days 1-10 of each cycle.
On days 2 and 9 they will come to the clinic to receive VIP152. This drug will be administered through a small plastic tube with a needle placed in a vein.
On day 11, participants will receive a fourth medication as an injection under the skin. They will rest and recover on days 12-21.
Screening tests will be repeated periodically throughout the study period.
Treatment will continue for up to 24 cycles.
Participants will have follow-up visits for up to 5 years.
Background:
Objectives:
INCLUSION CRITERIA:
Participants must have a histologically or cytologically confirmed lymphoid malignancy as listed below, confirmed by the Laboratory of Pathology, National Cancer Institute (NCI), as follows:
Relapsed and/or refractory disease, as defined below:
Must have evaluable disease by clinical exam (i.e., palpable lymphadenopathy, measurable skin lesions, etc.), laboratory assessment (i.e., disease involvement of bone marrow or peripheral blood by morphology, cytology or flow cytometry), and/or imaging (measurable lymph nodes, masses, or bony lesions on computed tomography (CT) or magnetic resonance imaging (MRI) and/or evaluable FD-Gavid lesions on positron emission tomography (PET).
NOTE: Lesions that have been irradiated cannot be included in the tumor assessment unless unequivocal tumor progression has been documented in these lesions after radiation therapy.
Age >= 18 years
Eastern Cooperative Oncology Group (ECOG) performance status <= 2
Adequate organ and marrow function as defined below unless dysfunction is secondary to disease:
OR
--Creatinine clearance**** >= 40 mL/min/1.73 m^2 for participants with creatinine levels above 2 mg/dL
Creatinine clearance (Cr Cl) will be calculated with the use of the 24-hour creatinine clearance or modified
Cockcroft-Gault equation (eCCR; with the use of ideal body mass [IBM] instead of mass): (140 - Age) x IBM (kg) x [0.85 if female] / 72 x serum creatinine (mg/dL)
*Red blood cell (RBC) transfusions and use of granulocyte colony-stimulating factor (G-CSF) will be allowed in order to meet eligibility parameters.
Total bilirubin must be <= 3 X institutional ULN for eligibility even if secondary to disease.
AST(SGOT)/ALT(SGPT) must be <= 5 X institutional ULN for eligibility even if secondary to disease.
Creatinine clearance must be >= 30 mL/min for eligibility even if secondary to disease.
Negative serum or urine pregnancy test must be obtained within 7 days before the first dose of study drug in individuals of childbearing potential. Postmenopausal individuals, as defined below, are allowed to enroll without a pregnancy test:
--Age >50 years with amenorrhea for at least 12 months or
--Age <=50 years with 6 months of spontaneous amenorrhea and follicle stimulating hormone (FSH) level within postmenopausal range (>40 mIU/mL) OR
Individuals of reproductive potential must agree to use highly effective contraception when sexually active. This applies for the period between signing of the informed consent and 90 days after the last administration of study drug.
Highly effective contraception includes:
In addition, participants must agree to use condoms.
EXCLUSION CRITERIA:
-The following restrictions apply to current or prior anti-cancer treatment, prior to the first dose of study drug:
NOTE: Exceptions to this include events not considered to place the participant at unacceptable risk of participation in the opinion of the principal investigator (PI) (e.g., alopecia).
-Participants requiring the following agents within 14 days or 5 half-lives of the drug (whichever is shorter) prior to the first dose of venetoclax and VIP152 are excluded:
NOTE: Moderate CYP3A inhibitors and inducers should be used with caution for participants in the dose-expansion cohorts and an alternative medication used, whenever possible.
Known allergy to both xanthine oxidase inhibitors and rasburicase; or known hypersensitivity to any of the study drugs
Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment, or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 2 weeks prior to first dose of study drug
HIV-positive participants
Active cytomegalovirus (CMV) infection as determined by a positive CMV polymerase chain reaction (PCR)
Active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection based on PCR assay; prior SARs-CoV-2 infection allowed if completely recovered from infection and negative PCR testing
Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis; as well as active infection with hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) except as noted above in inclusion criteria
Malabsorption syndrome or other condition that precludes enteral route of administration
History of other active malignancy requiring therapy that could affect compliance with the protocol or interpretation of results
Symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
Left ventricular ejection fraction (LVEF) < 45%
Clinically relevant findings on electrocardiogram (ECG) such as a second- or third-degree AV block or prolongation of the heart-rate corrected QT interval (Qtc) (Fridericia) over 470 msec (participants with atrioventricular (AV) block and pacemaker in place for >1 year and checked by a cardiologist within <6 months before the first dose of study drug, will not be excluded).
Uncontrolled intercurrent illness (including psychiatric) or social situations that may limit interpretation of results or that could increase risk to the participant