An open label, phase I/II study of Venetoclax in addition to Blinatumomab immunotherapy in adult patients with relapsed/refractory B cell precursor acute lymphoblastic leukemia (BCP-ALL)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Goethe University Frankfurt

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

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

Trial duration

11 Apr 2024 → ongoing

Decision date (initial)

2024-11-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2024-517959-12-00

EudraCT number

2021-001384-25

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

Phase I: determination of feasibility, safety and tolerability and maximum tolerated dose of
Venetoclax in combination with Blinatumomab.
Phase II: to evaluate the response in patients treated with the combination of Venetoclax and
Blinatumomab

Secondary objectives 1

1. To evaluate additional efficacy and safety of Venetoclax in combination with Blinatumomab and to improve quality of life of patients treated with Venetoclax/Blinatumomab combination

Conditions and MedDRA coding

Relapsed/refractory B cell precursor acute lymphoblastic leukemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Written informed consent in accordance with federal, local, and institutional guidelines. The patient must provide informed consent prior to the first screening procedure
2. Age ≥ 18 years
3. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
4. Availability of patient-specific molecular MRD markers of immunoglobulin/T-cell receptor gene rearrangements as assessed with a sensitivity of at least 10E-04
5. Diagnosis of Ph-negative, CD19-positive B-precursor acute lymphoblastic leukemia according to WHO classification: − Refractory BCP-ALL to primary induction therapy, including at least three cycles of standard chemotherapy − Untreated first relapse of BCP-ALL with first remission duration < 12 months or − Second or greater relapse of BCP-ALL or refractory relapse or − Relapse of BCP-ALL any time after allogeneic HSCT or
6. Positivity of MRD marker of immunoglobulin/T-cell receptor gene rearrangements of greater than 0.01% if in first or second remission of BCP-ALL
7. Negative pregnancy test < 7 days before first study drug in women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they fulfil at least one of the following criteria: − Post-menopausal (i.e. 12 months of natural amenorrhea or 6 months of amenorrhea with Serum FSH > 40 U/ml − Post-operative after bilateral ovariectomy with or without hysterectomy − Continuous and correct application of a contraception method with a Pearl index of < 1% (e.g. implants, depots, oral contraceptives, intrauterine device) from initial study drug administration until at least 3 months after the last dose of study drug. A hormonal contraception method must always be combined with a barrier method (e.g. condom) − Sexual abstinence − Vasectomy of the sexual partner
8. Ability to understand and willingness to sign a written informed consent
9. Willingness to participate in the registry of the German Multicenter Study Group for Adult ALL (GMALL)

Exclusion criteria 10

1. Patients with diagnosis of Philadelphia positive BCP-ALL according to WHO classification
2. Patients with diagnosis of Burkitt´s Leukemia according to WHO classification
3. Patients with extramedullary relapse; non-bulky lymph node (< 7.5 cm diameter) involvement will be accepted
4. Patients with CNS involvement at relapse (as determined by CSF analysis)
5. Patients with suspected or histologically confirmed testicular involvement at relapse
6. Current autoimmune disease of any kind or history of autoimmune disease with potential CNS involvement
7. Patients with Philadelphia-positive BCP-ALL still receiving TKI
8. Prior or concomitant therapy with BH3 mimetics
9. Prior therapy with anti CD19 therapy, unless administered in MRD-positive setting (i.e. with bone marrow blasts ≤ 5%)
10. Treatment with any of the following within 7 days prior to the first dose of study drug: strong cytochrome P450 3A (CYP3A) inhibitors, moderate or strong CYP3A inducers

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Phase I: Maximum tolerated dose (MTD) Phase II: mol-CR rate in patients with CR/CRh/CRi as assessed by molecular MRD analyses of bone marrow cells obtained after one treatment cycle

Investigational products

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

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Goethe University Frankfurt

Sponsor organisation

Goethe University Frankfurt

Address

Theodor-Stern-Kai 7

City

Frankfurt Am Main

Postcode

60590

Country

Germany

Scientific contact point

Organisation

Goethe University Frankfurt

Contact name

GMALL Studienzentrale

Public contact point

Organisation

Goethe University Frankfurt

Contact name

GMALL Studienzentrale

Locations

1 EU/EEA country · 19 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 14 files

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

Application history

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