Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Hematologic Neoplasms

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hematologic Diseases

Lymphosarcoma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Inflammatory Agents

Venetoclax

Prednisone

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

VVIP-VIP152 and venetoclax at escalating doses with prednisone at fixed doses to determine the MTD and RP2D of VIP152 and venetoclax

VVIP- VIP152 and venetoclax at the RP2D with prednisone at fixed doses

MYC rearrangement FISH testing is performed using the Vysis LSI MYC Break Apart Rearrangement Probe (Abbott Molecular, Inc.) in the Chromosome Pathology Section, Laboratory of Pathology, CCR, NCI. This kit is not FDA approved. It is being used as a treatment determining in-vitro diagnostic device in this study.

Vysis LSI MYC Break Apart Rearrangement Probe Kit

administered orally, days 1-10, per specified dose level; every 21 days for up to 12 cycles, or until disease progression or unacceptable toxicity

venetoclax

administered intravenously, days 2 and 9, per specified dose level; every 21 days for up to 12 cycles, or until disease progression or unacceptable toxicity

VIP152

administered orally, days 1-10, at a dose of 100 mg; every 21 days for up to 12 cycles, or until disease progression or unacceptable toxicity

prednisone

NCI Medical Oncology Referral Office

Christopher J Melani, M.D.

For more information at the NIH Clinical Center contact National Cancer Institute Referral Office

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 (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 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:

* High unmet medical need for relapsed/refractory non-Hodgkin lymphoma (NHL) after exhausting chemotherapy and/or chemo-immunotherapy regimens
* Targeted therapies aimed at disrupting cell death pathway in hematologic malignancies are emerging and showing significant activity in both the relapsed and first-line settings
* VIP152 is a selective inhibitor of PTEFb/CDK9 and is expected to show efficacy in tumor indications that overexpress MYC and MCL-1. VIP152 monotherapy has demonstrated a mild toxicity profile and preliminary efficacy in Phase 1 studies in advanced cancer
* The combination of VIP152 with venetoclax and prednisone (VVIP) targets major cell-death pathways in lymphoid malignancies (BCL-2 and MCL-1) and may overcome chemo-resistance and/or single drug resistance to venetoclax

Objectives:

* Phase 1: To determine the maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D), and the safety and toxicity profile of the combination of VIP152 with venetoclax and prednisone (VVIP) in relapsed/refractory lymphoid malignancies
* Phase 2: To determine the complete response (CR) rate of the combination of VIP152 with venetoclax and prednisone (VVIP) in R/R lymphoid malignancies

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

.All 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 dbGaP.

time measurement criteria are met for CR until the first date that progressive disease is objectively documented or death, assessed every 3-6months

time from date of study enrollment until time of disease relapse, disease progression, or death, whichever occurs first, assessed every 3-6 months

using the Kaplan-Meier method. Median, assessed during therapy and after completion of therapy from initiation of therapy to first response q3, 4, 6 and 12 months for post-treatment years 1, 2, 3, and 4-5, respectively, for up to 5 years after the last participant has enrolled on study

For ORR-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 or death, assessed every 3-6 months, For CR-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 or death, assessed every 3-6 months

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 or death, assessed every 3-6 months

time from the date of study enrollment until death from any cause, assessed every 3-6 months

time from the date of study enrollment until time of disease relapse, disease progression, alternative therapy for lymphoma given (such as radiation), or death, whichever occurs first, assessed every 3-6 months

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Study of VIP152, Venetoclax, and Prednisone (VVIP) in Relapsed/Refractory Lymphoid Malignancies	NCT05371054	Lymphoma Non-Hodgkin Lym... NHL Hematologic Mal... Lymphoid Malign...	Vysis LSI MYC B... venetoclax VIP152 prednisone	18 Years -	National Institutes of Health Clinical Center (CC)
Study of VIP152, Venetoclax, and Prednisone (VVIP) in Relapsed/Refractory Lymphoid Malignancies	NCT05371054	Lymphoma Non-Hodgkin Lym... NHL Hematologic Mal... Lymphoid Malign...	Vysis LSI MYC B... venetoclax VIP152 prednisone	18 Years -	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for vysis lsi myc break apart rearrangement probe kit