A Study to Evaluate VIP152 in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia or Richter Syndrome

Study Overview
=================
Brief Summary
-----------------
Determine the safety, tolerability, pharmacokinetics, maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of VIP152 as monotherapy or in combination with a BTKi in patients with Chronic Lymphocytic Leukemia (CLL) or Richter Syndrome

Official Title
-----------------
An Open-label, Multicenter Phase 1/1b Study to Characterize Safety, Tolerability, Preliminary Antitumor Activity, Pharmacokinetics, and Pharmacodynamics of VIP152 Monotherapy or Combination Therapy in Subjects With High-risk Chronic Lymphocytic Leukemia or Richter Syndrome

Conditions
-----------------
Relapsed Non Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, Refractory Chronic Lymphocytic Leukemia, Richter Syndrome, MYC Amplification, MYC Overexpression, MYC Translocation

Intervention / Treatment
-----------------
* Drug: VIP152
* Drug: BTKi


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female patients aged >/=18 years Adequate bone marrow, liver, and renal functions Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 Diseases as defined below: PART1 Subjects with CLL with either del(17p) by FISH or TP53 mutation who have received ≥1 prior therap(ies) and the last prior regimen must have included venetoclax plus an anti-CD20 antibody and/or a BTKi and did not produce complete remission. Subjects with CLL with either del(17p) by FISH or TP53 mutation who have received ≥2 prior regimens and are intolerant to BTKi and/or venetoclax are also eligible. or Subjects with CLL transformed to DLBCL who have relapsed after, or been refractory, to at least 1 prior line of therapy for DLBCL PART2 Subjects with CLL who are currently on an approved BTKi (monotherapy only) at the dose and schedule per the local label for ≥ 12 months who have only achieved SD, PR or PRL Exclusion Criteria: Active clinically serious infections of Grade > 2; requiring parenteral therapy Subjects who have new or progressive brain or meningeal or spinal metastases. Anticancer chemotherapy or immunotherapy during the study or within one week prior to the first dose of study drug Major surgery or significant trauma within 4 weeks before the first dose of study drug Allogeneic bone marrow transplant or stem cell rescue within 4 months before first dose of study drug; patients must have completed immunosuppressive therapy before enrollment

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Monotherapy of VIP152<br>Investigating VIP152 in a monotherapy cohort in patients with high-risk CLL and Richter Syndrome | Drug: VIP152<br>* Weekly IV infusion for 28 day cycles.<br>|
| Experimental: VIP152 in combination with BTKi<br>Investigating VIP152 in combination with a BTKi in patients with CLL | Drug: VIP152<br>* Weekly IV infusion for 28 day cycles.<br>Drug: BTKi<br>* Taken per local prescribing information<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability | Number of participants with adverse events as a measure safety and tolerability of high risk CLL and RS in monotherapy | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | Tumor response evaluation based on the response criteria as applicable for CLL and Richter Syndrome | Up to 3 years | 
| Duration of Response | Time at Which Response Criteria are Met for Complete Response or Partial Response (Whichever Occurs First) Until the First Date of Recurrence, Progression or Death per applicable response criteria | Up to 3 years | 
| Progression Free Survival | Number of Participants Without Disease Progression per iwCLL guidelines for CLL & Lugano Classification for NHL | Up to 3 years | 
| Assessment of pharmacokinetics (PK) of VIP152 | Maximum observed drug concentration in measured administration (Cmax) of VIP152 | Cycle 1 Day 1 through Cycle 2 Day 1 | 
| Time To Next Treatment | time from first dose to the initiation of next dose or death | Up to 3 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
CDK-9, CLL, Leukemia, VIP152, Richter Syndrome, BTKi