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
2 other identifiers
interventional
8
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1 lymphoma
Started Apr 2023
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 11, 2022
CompletedFirst Posted
Study publicly available on registry
May 12, 2022
CompletedStudy Start
First participant enrolled
April 5, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 22, 2024
CompletedResults Posted
Study results publicly available
April 8, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
December 16, 2025
CompletedFebruary 23, 2026
February 1, 2026
1.3 years
May 11, 2022
February 26, 2025
February 10, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (5)
Phase 2: Complete Response (CR) Rate
CR rate is defined as the percentage of participants who meet criteria for complete response (CR) as measured by the Lugano Classification Response Criteria for Non-Hodgkin lymphoma (NHL). Complete response is defined as target nodes/nodal masses that regress to \<1.5 cm in longest transverse diameter of a lesion (LDi).
24 cycles (i.e., 72 weeks)
Phase 1: Number of Solicited and/or Non-solicited Non-serious Adverse Events (AE's) With Grade
Number of non-serious adverse events (AE's) with grade was assessed by the CTCAEv5.0. A non-serious adverse event is any untoward medical occurrence that does not meet seriousness criteria. Grade 1 is mild. Grade 2 is moderate. Grade 3 is serious. Grade 4 if life-threatening.
Up to 18 weeks.
Phase 1: Number of Solicited and/or Unsolicited Serious Adverse Events (SAE's) With Grade
Number of serious adverse events (SAE's) with grade was assessed by the CTCAEv5.0. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is fatal.
Up to 18 weeks.
Phase 1: Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D)
The MTD/RP2D is the dose level at which no more than 1 of up to 6 participants experience dose limiting toxicity (DLT) during the DLT evaluation window(s), or the dose below that at which at least 2 (of ≤6) participants have DLT. A DLT (dose-limiting toxicity) is defined as a grade 3 or higher adverse event (AE) that occurs in the dose-escalation cohort within the first 22 days after initiation of VVIP (i.e., Cycle 1, Day 1 to Cycle 2, Day 1 pre-dose) and is considered related to study drug (i.e., VIP152, venetoclax, and/or prednisone) or a treatment delay of cycle 2 of \> 7 days for hematologic or nonhematologic toxicities.
First 22 days (i.e., cycle 1, day 1 to cycle 2, day 1 pre-dose)
Phase 1: Number of Participants With Grade 4 Neutropenia Dose-Limiting Toxicity (DLT)
A DLT (dose-limiting toxicity) is defined as a grade 3 or higher adverse event (AE) that occurs in the dose-escalation cohort within the first 22 days after initiation of VVIP (i.e., Cycle 1, Day 1 to Cycle 2, Day 1 pre-dose) and is considered related to study drug (i.e., VIP152, venetoclax, and/or prednisone) or a treatment delay of cycle 2 of \> 7 days for hematologic or nonhematologic toxicities.
First 22 days (i.e., cycle 1, day 1 to cycle 2, day 1 pre-dose)
Secondary Outcomes (6)
Phase 1: Progression-free Survival (PFS)
Assessed from date of study enrollment until time of disease relapse, disease progression, death, or last follow-up, whichever comes first, up to 8 months
Phase 1: Time to Response (TTR)
Time from the date of study enrollment during therapy, after completion of therapy from initiation of therapy to first response, up to 5 months
Phase 1: Duration of Response (DOR)
Time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 5 months
Phase 1: Overall Response Rate (ORR)
24 cycles (i.e., 72 weeks)
Phase 1: Overall Survival (OS)
Assessed from the date of study enrollment until death from any cause, or last follow-up, whichever occurs first, up to a maximum of 32 months.
- +1 more secondary outcomes
Other Outcomes (1)
Phase 1: Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)
24 cycles (i.e., 72 weeks)
Study Arms (2)
Cohort 1/Phase 1: Arm 1 Dose Escalation
EXPERIMENTALEnitociclib (VIP152), Venetoclax and prednisone (VVIP) - VIP152 and venetoclax at escalating doses with prednisone at fixed doses to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of VIP152 and venetoclax.
Cohort 2/Phase 2: Arm 2 Dose Expansion
EXPERIMENTALEnitociclib (VIP152), Venetoclax and prednisone (VVIP) - VIP152 and venetoclax at the recommended phase II dose (RP2D) with prednisone at fixed doses.
Interventions
MYC rearrangement fluorescence in situ hybridization (FISH) testing is performed using the Vysis LSI MYC Break Apart Rearrangement Probe (Abbott Molecular, Inc.) in the Chromosome Pathology Section, Laboratory of Pathology, Center for Cancer Research (CCR), National Cancer Institute (NCI). This kit is not Food and Drug Administration (FDA) approved. It is being used as a treatment determining in-vitro diagnostic device in this study.
Dose Escalation: Administered orally, days 1-10, per specified dose level; every 21 days for up to 24 cycles, or until disease progression or unacceptable toxicity. Dose Expansion: Administered orally, days 1-10, at the recommended phase 2 dose (RP2D); every 21 days for up to 24 cycles, or until disease progression or unacceptable toxicity
Dose Escalation: Administered intravenously, days 2 and 9, per specified dose level; every 21 days for up to 24 cycles, or until disease progression or unacceptable toxicity. Dose Expansion: Administered intravenously, days 2 and 9, at the recommended phase 2 dose (RP2D); every 21 days for up to 24 cycles, or until disease progression or unacceptable toxicity.
Administered orally, days 1-10, at a dose of 100 mg; every 21 days for up to 24 cycles, or until disease progression or unacceptable toxicity
Screening, pre-cycle 7, pre-cycle 13, and at end-of-treatment (post-cycle 24).
Screening
Screening
Screening, pre-cycle 2, pre-cycle 3, pre-cycle 5, pre-cycle 7, pre-cycle 9, pre-cycle 11, pre-cycle 13, pre-cycle 15, pre-cycle 17, pre-cycle 19, pre-cycle 21, pre-cycle 23, and at end-of-treatment (post cycle 24).
As indicated. Screening, pre-cycle 2, pre-cycle 3, pre-cycle 5, pre-cycle 7, pre-cycle 9, pre-cycle 11, pre-cycle 13, pre-cycle 15, pre-cycle 17, pre-cycle 19, pre-cycle 21, pre-cycle 23, and at end-of-treatment (post cycle 24).
Baseline, post-cycle 6, post-cycle 12, and at end-of-treatment (post-cycle 24).
Eligibility Criteria
You may qualify if:
- 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:
- Refractory/relapsed (R/R) MYC-rearranged diffuse large B-cell lymphoma (DLBCL)/High-grade B-cell lymphoma (HGBCL) (MYC aberration must be confirmed by NCI Laboratory of Pathology to enroll)
- R/R non-germinal center B-cell (non-GCB) DLBCL without MYC-rearrangement (Cell of origin (COO) and non-MYC aberration must be confirmed by NCI Laboratory of Pathology to enroll. COO determination at enrollment will utilize immunohistochemistry and Han's algorithm)
- R/R Peripheral T-cell lymphoma (PTCL-not otherwise specified (NOS), PTCL-T follicular helper (TFH), follicular T-cell lymphoma (TCL), angioimmunoblastic T-cell lymphoma (AITL), adult T-cell leukemia/lymphoma (ATLL), anaplastic lymphoma kinase (ALK)+ anaplastic large-cell lymphoma (ALCL) and ALK- ALCL per 2016 World Health Organization (WHO) classification)
- Relapsed and/or refractory disease, as defined below:
- Aggressive B-cell lymphoma: relapsed after and/or refractory to at least 2 prior systemic therapies, 1 or more which includes an anthracycline and anti-cluster of differentiation 20 (CD20) targeting agent
- PTCL: relapsed after and/or refractory to at least 2 prior systemic therapies, 1 or more which includes an anthracycline (and a brentuximab vedotin-containing regimen for participants with ALK+ or ALK- ALCL)
- 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:
- Absolute neutrophil count\* \>=1,000/mcL
- Hemoglobin\* \>=8 g/dL
- Platelets \>=75,000/mcL
- +25 more criteria
You may not qualify if:
- The following restrictions apply to current or prior anti-cancer treatment, prior to the first dose of study drug:
- Participants who are actively receiving any other anti-cancer investigational agents.
- Any chemotherapy, targeted therapy, or anti-cancer antibodies within 2 weeks prior to the first dose of study drug
- Radio- or toxin-immunoconjugates within 10 weeks prior to the first dose of study drug
- Prior allogeneic stem cell (or other organ) transplant within 6 months or any evidence of active graft-versus-host disease or requirement for immunosuppressants within 28 days prior to first dose of study drug
- Not recovered (i.e., \<= Grade 1 or baseline) from adverse events due to previously administered anti-cancer treatment, surgery, or procedure.
- 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:
- Strong cytochrome P450, family 3, subfamily A (CYP3A) inhibitors
- Strong CYP3A inducers
- Moderate CYP3A inhibitors (dose-escalation cohort only)
- Moderate CYP3A inducers (dose-escalation cohort only)
- 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
- +11 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Related Publications (1)
Frigault MM, Mithal A, Wong H, Stelte-Ludwig B, Mandava V, Huang X, Birkett J, Johnson AJ, Izumi R, Hamdy A. Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription. Cancer Res Commun. 2023 Nov 9;3(11):2268-2279. doi: 10.1158/2767-9764.CRC-23-0219.
PMID: 37882668DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Christopher J. Melani
- Organization
- National Cancer Institute
Study Officials
- PRINCIPAL INVESTIGATOR
Christopher J Melani, M.D.
National Cancer Institute (NCI)
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- NIH
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
May 11, 2022
First Posted
May 12, 2022
Study Start
April 5, 2023
Primary Completion
July 22, 2024
Study Completion
December 16, 2025
Last Updated
February 23, 2026
Results First Posted
April 8, 2025
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Clinical data will be available during the study and indefinitely. Genomic data will be available once genomic data are uploaded per protocol Genomic Data Sharing (GDS) plan for as long as database is active.
- Access Criteria
- Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI). Genomic data will be made available via the database of Genotypes and Phenotypes (dbGaP) through requests to the data custodians.
All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. In addition, all large-scale genomic sequencing data will be shared with subscribers to the database of Genotypes and Phenotypes (dbGaP).