CD19- and CD22-directed CAR-T Cell Therapy in Patients With Acute Lymphoblastic Leukemia

Study Overview
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Brief Summary
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This is a first-in-human study to evaluate the feasibility, safety and preliminary antitumor efficacy of autologous chimeric antigen receptor (CAR) T cells targeting both CD19 and CD22, manufactured with T-Charge(TM) process. CAR-T cells will be investigated as single agent in pediatric and adult acute lymphoblastic leukemia (ALL).

Detailed Description
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This is a phase I, open label, multicenter, dose escalation and expansion study of IMJ995. The study will investigate single agent IMJ995 in two independent groups of acute lymphoblastic leukemia (ALL) patients: Pediatric, adolescent and young adult (AYA) ALL patients up to 29 years old Adult ALL patients (≥30 years old) safety cohort The pediatric and AYA ALL group consists of two parts: a dose escalation part to evaluate feasibility, characterize safety and identify the recommended dose (RD) of IMJ995, and a dose expansion part to further characterize safety, cellular kinetics and assess preliminary antitumor activity. Once the RD of IMJ995 is determined for this group, the corresponding expansion part may commence. Once the RD of IMJ995 is determined for the pediatric and AYA group, a safety cohort for adult ALL patients ≥30 years old may commence in parallel to the above mentioned expansion part.

Official Title
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Phase I, Open Label, Multicenter, Dose Escalation and Expansion Study of IMJ995 in Acute Lymphoblastic Leukemia

Conditions
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Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Drug: IMJ995 single agent


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients: Evidence of CD19 and/or CD22 cell surface expression on B-ALL blasts in bone marrow or peripheral blood by flow cytometry at time of relapse or prior to study entry. Pediatric, adolescent and young adult ALL patients: 1 - 29 years of age at the time of informed consent form (ICF) signature. Relapsed or refractory CD19+ and/or CD22+ ALL after 3 or more lines of treatment OR after allogeneic HCT. Must have received a CD19-directed CAR-T treatment (with or without blinatumomab), unless prior loss of CD19 cell surface expression occurred or have not been eligible for CD19 directed CAR-T treatment. Lansky (age < 16 years), Karnofsky (age 16-25 years) performance status ≥ 60%. ECOG (age >25 years) performance status that is either 0 or 1 at screening. Adult ALL patients aged ≥30 years: ≥30 years of age at the time of informed consent form (ICF) signature. Refractory or relapsed CD19+ and/or CD22+ ALL including at least one of the following: After allogeneic HCT After 2 or more lines of treatment, including blinatumomab and/or inotuzumab Primary refractory disease (defined as failure to achieve a CR at the end of at least 1 induction chemotherapy) First relapse occurring within 12 months from first remission ECOG performance status that is either 0 or 1 at screening. Exclusion Criteria: Allogeneic HCT within 12 weeks prior to screening. Presence of isolated extra-medullary disease, testicular involvement or bulky disease Patients with concomitant genetic syndromes associated with bone marrow failure states: such as patients with Fanconi anemia, Kostmann syndrome, Shwachman syndrome. Patients with Burkitt's lymphoma/leukemia History of active neurological auto immune or inflammatory disorders Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 1 Year

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IMJ995 in ALL<br>Dose escalation and expansion of IMJ995 single agent in ALL | Drug: IMJ995 single agent<br>* Single intravenous administration of IMJ995<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and nature of Dose Limiting Toxicities (Dose Escalation part only, in pediatric, adolescent and young adult ALL patients) | Dose recommendation for IMJ995 in pediatric, adolescent and young adult ALL patients | 28 days | 
| Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) (pediatric, adolescent and young adult ALL patients) | Safety and tolerability | 24 months | 
| Number of patients infused with planned target dose | Manufacture success rate | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and nature of DLTs during the first 28 days after IMJ995 infusion (safety cohort for adult ALL). | Dose recommendation in adult ALL | 28 days | 
| Cellular kinetics of IMJ995 (maximum drug concentration - Cmax) | CAR transgene levels will be measured by flow cytometry and quantitative polymerase chain reaction (qPCR) in peripheral blood. PK parameters will be determined using non-compartmental methods for IMJ995. | 24 months | 
| Cellular kinetics of IMJ995 (area under the drug concentration-time curve - AUC) | CAR transgene levels will be measured by flow cytometry and quantitative polymerase chain reaction (qPCR) in peripheral blood. PK parameters will be determined using non-compartmental methods for IMJ995. | 24 months | 
| Number of participants with anti-CAR19 and/or anti-CAR22 antibodies | Humoral immunogenicity | 24 months | 
| Change from baseline in interferon (IFN)-gamma levels in peripheral blood mononuclear cells (PBMCs) | Cellular immunogenicity | 24 months | 
| Antitumor activity assessed by Complete Remission / Complete Remission with Incomplete Hematologic Recovery (CR/ CRi). | Antitumor activity | 24 months | 
| Antitumor activity assessed by duration of response. | Duration of response | 24 months | 
| Incidence and severity of AEs and SAEs after IMJ995 infusion (safety cohort for adult ALL). | Safety and tolerability | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CAR-T, IMJ995, CD19, CD22, acute lymphoblastic leukemia (ALL), pediatric, adolescent