Clinical trial • Phase I/II • Haematology

VENETOCLAX for B-cell precursor acute lymphoblastic leukemia (relapsed/refractory)

Phase I/II trial of VENETOCLAX for B-cell precursor acute lymphoblastic leukemia (relapsed/refractory). open-label, adaptive. 21 participants.

Overview

Trial Therapeutic Area
Haematology
Trial Disease
B-cell precursor acute lymphoblastic leukemia (relapsed/refractory)
Trial Stage
Phase I/II
Drug Modality
Small molecule|Bispecific antibody

Key dates

Initial CTIS Submission Date
16-10-2024
First CTIS Authorization Date
05-11-2024

Trial design

open-label, adaptive Phase I/II trial across 18 sites in Germany.

Open Label
Yes
Adaptive
True - Phase I dose-escalation design to determine feasibility, safety, tolerability and maximum tolerated dose (MTD) of Venetoclax in combination with Blinatumomab (dose-escalation rules/interim analyses/stopping rules not detailed in provided data).
Single Multiple Or Escalation Dose Combined
Yes
Target Sample Size
21

Eligibility

Recruits 21 No vulnerable populations selected. All participants must be ≥ 18 years and must provide written informed consent prior to the first screening procedure in accordance with federal, local and institutional guidelines. No assent procedures or paediatric consent described..

Pregnancy Exclusion
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
Vulnerable Population
No vulnerable populations selected. All participants must be ≥ 18 years and must provide written informed consent prior to the first screening procedure in accordance with federal, local and institutional guidelines. No assent procedures or paediatric consent described.

Inclusion criteria

  • {"criterion_text":"- Written informed consent in accordance with federal, local, and institutional guidelines. The patient must provide informed consent prior to the first screening procedure\n- Age ≥ 18 years\n- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2\n- Availability of patient-specific molecular MRD markers of immunoglobulin/T-cell receptor gene rearrangements as assessed with a sensitivity of at least 10E-04\n- 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\n- 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\n- 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\n- Ability to understand and willingness to sign a written informed consent\n- Willingness to participate in the registry of the German Multicenter Study Group for Adult ALL (GMALL)"}

Exclusion criteria

  • {"criterion_text":"- Patients with diagnosis of Philadelphia positive BCP-ALL according to WHO classification\n- 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\n- Patients with diagnosis of Burkitt´s Leukemia according to WHO classification\n- Patients with extramedullary relapse; non-bulky lymph node (< 7.5 cm diameter) involvement will be accepted\n- Patients with CNS involvement at relapse (as determined by CSF analysis)\n- Patients with suspected or histologically confirmed testicular involvement at relapse\n- Current autoimmune disease of any kind or history of autoimmune disease with potential CNS involvement\n- Patients with Philadelphia-positive BCP-ALL still receiving TKI\n- Prior or concomitant therapy with BH3 mimetics\n- Prior therapy with anti CD19 therapy, unless administered in MRD-positive setting (i.e. with bone marrow blasts ≤ 5%)"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- 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","definition_or_measurement_approach":"Phase I: determination of Maximum tolerated dose (MTD). Phase II: molecular complete remission (mol-CR) rate in patients with CR/CRh/CRi assessed by molecular minimal residual disease (MRD) analyses of bone marrow cells obtained after one treatment cycle."}

Recruitment

Registry Or Advocacy Recruitment
True - German Multicenter Study Group for Adult ALL (GMALL) registry
Planned Sample Size
21
Recruitment Window Months
50
Consent Approach
Written informed consent required prior to first screening procedure in accordance with federal, local and institutional guidelines. Participants must be able to understand and willing to sign written informed consent; adults only (≥18). Participant information and informed consent form available (GMALL-BLIVEN_Patienteninformation_V3-0_20240906). Languages not specified.

Geography

Total Number Of Sites
18
Total Number Of Participants
21

Germany

Earliest CTIS Part Ii Submission Date
29-10-2024
Latest Decision Or Authorization Date
06-11-2025
Processing Time Days
373
Number Of Sites
18
Number Of Participants
21

Sites

Site Name
University Hospital Cologne AöR
Department Name
Klinik I für Innere Medizin
Principal Investigator Name
Boris Böll
Principal Investigator Email
boris.boell@uk-koeln.de
Contact Person Name
Boris Böll
Contact Person Email
boris.boell@uk-koeln.de
Site Name
Universitaetsklinikum Essen AöR
Department Name
Klinik für Hämatologie und Stammzelltransplantation
Principal Investigator Name
Maher Hanoun
Principal Investigator Email
maher.hanoun@uk-essen.de
Contact Person Name
Maher Hanoun
Contact Person Email
maher.hanoun@uk-essen.de
Site Name
Technische Universitaet Dresden
Department Name
Medizinische Klinik und Poliklinik I
Principal Investigator Name
Lisa Heberling
Principal Investigator Email
lisa.heberling@ukdd.de
Contact Person Name
Lisa Heberling
Contact Person Email
lisa.heberling@ukdd.de
Site Name
Universitaetsklinikum Duesseldorf AöR
Department Name
Klinik für Hämatologie, Onkologie und Klinische Immunologie
Principal Investigator Name
Kathrin Nachtkamp
Principal Investigator Email
kathrin.nachtkamp@med.uni-duesseldorf.de
Contact Person Name
Kathrin Nachtkamp
Site Name
Goethe University Frankfurt
Department Name
Hämatologie/Onkologie
Principal Investigator Name
Nicola Gökbuget
Principal Investigator Email
goekbuget@em.uni-frankfurt.de
Contact Person Name
Nicola Gökbuget
Contact Person Email
goekbuget@em.uni-frankfurt.de
Site Name
Universitaetsklinikum Schleswig-Holstein AöR
Department Name
Hämatologie und Onkologie
Principal Investigator Name
Lars Fransecky
Principal Investigator Email
Lars.Fransecky@uksh.de
Contact Person Name
Lars Fransecky
Contact Person Email
Lars.Fransecky@uksh.de
Site Name
Universitaetsklinikum Tuebingen AöR
Department Name
Innere Medizin II
Principal Investigator Name
Christop Faul
Principal Investigator Email
christoph.faul@med.uni-tuebingen.dede
Contact Person Name
Christop Faul
Site Name
Klinikum Oldenburg AöR
Department Name
Onkologie und Hämatologie
Principal Investigator Name
Andreas Voß
Principal Investigator Email
voss.andreas@klinikum-oldenburg.de
Contact Person Name
Andreas Voß
Site Name
Klinikum rechts der Isar der TU Muenchen AöR
Department Name
Klinik und Poliklinik für Innere Medizin III
Principal Investigator Name
Folker Schneller
Principal Investigator Email
folker.schneller@mri.tum.de
Contact Person Name
Folker Schneller
Contact Person Email
folker.schneller@mri.tum.de
Site Name
Universitaet Leipzig
Department Name
Klinik und Poliklinik für Hämatologie, Zelltherapie, Hämostaseologie und Infektiologie
Principal Investigator Name
Vladan Vucinic
Principal Investigator Email
vladan.vucinic@medizin.uni-leipzig.de
Contact Person Name
Vladan Vucinic
Site Name
Heidelberg University
Department Name
III. Medizinische Klinik; Hämatoonkologie
Principal Investigator Name
Daniela Heidenreich
Principal Investigator Email
daniela.heidenreich@umm.de
Contact Person Name
Daniela Heidenreich
Contact Person Email
daniela.heidenreich@umm.de
Site Name
Universitaetsklinikum Ulm AöR
Department Name
Klinik für Innere Medizin III
Principal Investigator Name
Andreas Viardot
Principal Investigator Email
andreas.viardot@uniklinik-ulm.de
Contact Person Name
Andreas Viardot
Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
Med. Klinik m. S. Hämatologie, Onkologie und Tumorimmunologie
Principal Investigator Name
Stefan Schwartz
Principal Investigator Email
stefan.schwartz@charite.de
Contact Person Name
Stefan Schwartz
Contact Person Email
stefan.schwartz@charite.de
Site Name
Robert Bosch Gesellschaft fuer medizinische Forschung mbH
Department Name
Abteilung Hämatologie, Onkologie und Palliativmedizin
Principal Investigator Name
Sonja Martin
Principal Investigator Email
sonja.martin@rbk.de
Contact Person Name
Sonja Martin
Contact Person Email
sonja.martin@rbk.de
Site Name
Universitaetsklinikum Heidelberg AöR
Department Name
Innere Medizin V, Hematologie, Onkologie, Rheumatologie
Principal Investigator Name
Simon Raffel
Principal Investigator Email
simon.raffel@med.uni-heidelberg.de
Contact Person Name
Simon Raffel
Site Name
University Medical Center Hamburg-Eppendorf
Department Name
Zentrum für Onkologie; Abteilung für Onkologie, Hämatologie und Knochenmarktransplantation
Principal Investigator Name
Franziska Modemann
Principal Investigator Email
f.modemann@uke.de
Contact Person Name
Franziska Modemann
Contact Person Email
f.modemann@uke.de
Site Name
Klinikum der Universitaet Muenchen AöR
Department Name
Hämatologie der Medizinischen Klinik III
Principal Investigator Name
Veit Bücklein
Principal Investigator Email
veit.buecklein@med.uni-muenchen.de
Contact Person Name
Veit Bücklein
Site Name
Universitaetsklinikum Erlangen AöR
Department Name
Med. Klinik 5, Hämatologie und int. Onkologie
Principal Investigator Name
Bernd Spriewald
Principal Investigator Email
bernd.spriewald@uk-erlangen.de
Contact Person Name
Bernd Spriewald
Contact Person Email
bernd.spriewald@uk-erlangen.de

Sponsor

Primary sponsor

Full Name
Goethe University Frankfurt
Organisation Type
Educational Institution
Country Of Registered Address
Germany

Investigational products

Investigational Product Name
Venclyxto (venetoclax) film-coated tablets (10 mg / 50 mg / 100 mg)
Active Substance
VENETOCLAX
Modality
Small molecule
Routes Of Administration
Oral
Route
Oral
Authorisation Status
Authorised (marketing authorisation present: EU/1/16/1138)
Investigational Product Name
BLINCYTO 38.5 micrograms powder for concentrate and solution for solution for infusion (blinatumomab)
Active Substance
BLINATUMOMAB
Modality
Bispecific antibody
Routes Of Administration
Intravenous
Route
Intravenous
Authorisation Status
Authorised (marketing authorisation present: EU/1/15/1047)
Combination Treatment
Yes

Related trials

Other published trials that may interest you.