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

Primary Purpose

Acute Lymphoblastic Leukemia

Status

Withdrawn

Phase

Phase 1

Locations

Study Type

Interventional

Intervention

IMJ995 single agent

About this trial

This is an interventional treatment trial for Acute Lymphoblastic Leukemia focused on measuring CAR-T, IMJ995, CD19, CD22, acute lymphoblastic leukemia (ALL), pediatric, adolescent

Eligibility Criteria

1 Year - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

IMJ995 in ALL

Arm Description

Dose escalation and expansion of IMJ995 single agent in ALL

Outcomes

Primary Outcome Measures

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

Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) (pediatric, adolescent and young adult ALL patients)

Safety and tolerability

Number of patients infused with planned target dose

Manufacture success rate

Secondary Outcome Measures

Incidence and nature of DLTs during the first 28 days after IMJ995 infusion (safety cohort for adult ALL).

Dose recommendation in adult ALL

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.

Cellular kinetics of IMJ995 (area under the drug concentration-time curve - AUC)

Number of participants with anti-CAR19 and/or anti-CAR22 antibodies

Humoral immunogenicity

Change from baseline in interferon (IFN)-gamma levels in peripheral blood mononuclear cells (PBMCs)

Cellular immunogenicity

Antitumor activity assessed by Complete Remission / Complete Remission with Incomplete Hematologic Recovery (CR/ CRi).

Antitumor activity

Antitumor activity assessed by duration of response.

Duration of response

Incidence and severity of AEs and SAEs after IMJ995 infusion (safety cohort for adult ALL).

Safety and tolerability

Full Information

NCT ID

NCT05168748

First Posted

November 3, 2021

Last Updated

December 20, 2022

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT05168748

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2022

Overall Recruitment Status

Withdrawn

Why Stopped

Sponsor's decision

Study Start Date

January 24, 2023 (Anticipated)

Primary Completion Date

August 13, 2026 (Anticipated)

Study Completion Date

August 13, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Lymphoblastic Leukemia

Keywords

CAR-T, IMJ995, CD19, CD22, acute lymphoblastic leukemia (ALL), pediatric, adolescent

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

IMJ995 in ALL

Arm Type

Experimental

Arm Description

Dose escalation and expansion of IMJ995 single agent in ALL

Intervention Type

Drug

Intervention Name(s)

IMJ995 single agent

Intervention Description

Single intravenous administration of IMJ995

Primary Outcome Measure Information:

Title

Incidence and nature of Dose Limiting Toxicities (Dose Escalation part only, in pediatric, adolescent and young adult ALL patients)

Description

Dose recommendation for IMJ995 in pediatric, adolescent and young adult ALL patients

Time Frame

28 days

Title

Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) (pediatric, adolescent and young adult ALL patients)

Description

Safety and tolerability

Time Frame

24 months

Title

Number of patients infused with planned target dose

Description

Manufacture success rate

Time Frame

24 months

Secondary Outcome Measure Information:

Title

Incidence and nature of DLTs during the first 28 days after IMJ995 infusion (safety cohort for adult ALL).

Description

Dose recommendation in adult ALL

Time Frame

28 days

Title

Cellular kinetics of IMJ995 (maximum drug concentration - Cmax)

Description

Time Frame

24 months

Title

Cellular kinetics of IMJ995 (area under the drug concentration-time curve - AUC)

Description

Time Frame

24 months

Title

Number of participants with anti-CAR19 and/or anti-CAR22 antibodies

Description

Humoral immunogenicity

Time Frame

24 months

Title

Change from baseline in interferon (IFN)-gamma levels in peripheral blood mononuclear cells (PBMCs)

Description

Cellular immunogenicity

Time Frame

24 months

Title

Antitumor activity assessed by Complete Remission / Complete Remission with Incomplete Hematologic Recovery (CR/ CRi).

Description

Antitumor activity

Time Frame

24 months

Title

Antitumor activity assessed by duration of response.

Description

Duration of response

Time Frame

24 months

Title

Incidence and severity of AEs and SAEs after IMJ995 infusion (safety cohort for adult ALL).

Description

Safety and tolerability

Time Frame

24 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

1 Year

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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