A trial to understand if AZD0486 is safe and helps in people with Relapsed or Refractory B-cell acute lymphoblastic leukemia (B-ALL)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Astrazeneca AB

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

16 Aug 2024 → ongoing

Decision date (initial)

2024-05-03

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2023-505840-20-00

ClinicalTrials.gov

NCT06137118

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Therapy, Dose response, Pharmacodynamic, Safety, Efficacy

Part A: To assess the safety and tolerability of AZD0486 in participants with Ph(+) or Ph(-) R/R B-ALL, aged 12 years and above
Part B: To assess the safety and tolerability of AZD0486 in participants with Ph(+) or Ph(-) R/R B-ALL, aged 12 years and above
Parts B & C: To evaluate the efficacy of AZD0486 in participants with Ph(+) or Ph(-) R/R B-ALL, aged 12 years and above

Secondary objectives 5

1. Parts A, B, C: To evaluate the efficacy of AZD0486
2. Parts A, B, C: To characterise the PK parameters of AZD0486 as monotherapy
3. Parts A, B, C: To evaluate the immunogenicity of AZD0486 as monotherapy
4. Parts B, C: To evaluate the impact of AZD0486 on MRD-negative CR rate
5. Part C: To assess the safety, tolerability of AZD0486 in participants with R/R B-ALL aged 12 to 80 years, inclusive

Conditions and MedDRA coding

B-Cell Acute Lymphoblastic Leukaemia

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Age: 16-80 years old for dose escalation cohorts; ≥ 12 years for backfills (Part A), ≥ 12 years old (Parts B and C).
2. Participants with CD19+ B-cell Acute Lymphoblastic Leukemia by local lab with Bone marrow infiltration with >/= 5% blasts
3. Participants with CD19+ B-cell Acute Lymphoblastic Leukemia by local lab with Either relapsed or refractory after a minimum of 2 prior therapies or after 1 prior line of therapy if no SOC available option.
4. Participants with CD19+ B-cell Acute Lymphoblastic Leukemia by local lab with Philadelphia positive participants are allowed in All Parts if intolerant or refractory to TKIs.
5. Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 2 OR Lansky score more or equal to 50%.

Exclusion criteria 8

1. Active CNS involvement by B-ALL, defined by presence of ALL blasts in CSF (CNS2 and CNS3 criteria).
2. Isolated extramedullary disease relapse.
3. Testicular leukemia
4. History or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome, or psychosis; or prior Grade 4 neurotoxicity with CAR-T or TCE therapy.
5. History of other malignancy (with certain exceptions).
6. Unresolved AEs >/= Grade 2, from prior therapies
7. Prior therapy with TCEs within 4 weeks, CAR T-cell therapy or autologous HSCT within 8 weeks or prior alloSCT within 12 weeks of start of therapy.
8. GVHD requiring immunosuppressive therapy within 3 weeks prior to AZD0486 treatment.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Part A: Frequency of DLTs
2. Part A,B Safety Evaluation of AZD0486
3. Part B, C: Rate of CR within 3 cycles

Secondary endpoints 10

1. Part A: Rate of CR within 3 cycles
2. Part A,B,C: Rate of CR/CRh and CR/CRh/CRi within 3 cycles
3. Part A,B,C: Rate of CR, CR/CRh and CR/CRh/CRi at any time during study
4. Part A, B, C: Duration of CR, CR/CRh and CR/CRh/CRi
5. Part A, B, C: Event-free survival (EFS)
6. Part A, B, C: Overall Survival (OS)
7. Part B, C: Subsequent alloSCT or donor lymphocyte infusion if used as an alloSCT substitute
8. Part A, B, C: MRD-negative rate of CR, CR/CRh and CR/CRh/CRi
9. Part A, B, C: PK Characterization of AZD0486 (UC, Cmax, tmax, Ctrough, t1/2 and CL of AZD0486)
10. Part A, B, C: ADA Characterization of AZD0486

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Astrazeneca AB

Sponsor organisation

Astrazeneca AB

Address

Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

Astrazeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

Astrazeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Locations

4 EU/EEA countries · 29 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 4 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 54 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

11 submissions — initial application plus substantial / non-substantial modifications