Isatuximab in Adult Patients With Cytologic or Molecular Relapsed/Refractory CD38 Positive T-cell Acute Lymphoblastic Leukemia

NCT06648889 | Recruiting Phase 2 DMC

• 3 other identifiers: GMALL-Isatuximab2023-507899-47-002023
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 15

Brief Summary

The planned trial offers treatment cohorts for patients with full cytologic relapse (R/R ALL - Cohort 1), as well as for patients with molecular failure/relapse (MRD+ ALL - Cohort 2). Basically, the study aims to develop data for optimization of first-line therapy of T-ALL, either by modification of standard induction with Isatuximab or by establishing a post-induction therapy for eradication of MRD and thereby evaluates in parallel two different strategies.

Conditions

T-ALL

Keywords

R/R or MRD CD38-positive T-ALL

Outcome Measures

Primary Outcomes (3)

• Proportion of patients with complete hematologic response (ORR= CR and CRi)

  Cohort 1: Proportion of patients with complete hematologic response (ORR= CR and CRi) after 2 cycles of induction therapy including Isatuximab.

  Day 22, Week 9, per SoC

• Overall incidence and severity of adverse events

  Cohort 1: Overall incidence and severity of adverse events (CTCAE 5.0).

  Day 22, Week 9, month 3, month 6 (depends on duration of therapy which is variable)

• Proportion of patients with molecular response (MolCR)

  Cohort 2: Proportion of patients with molecular response (MolCR) after one cycle of Isatuximab.

  Day 22, Week 9, per SoC

Secondary Outcomes (14)

• Proportion of patients with CR and CRi, MolCR and cMolCR in R/R

  Day 22, Week 9, per SoC

• Probability of continuous complete remission

  at 18 months

• Probability of overall survival

  at 18 Months

• Probability of relapse-free survival

  at 18 months

• Probability of event-free survival

  at 18 months

Study Arms (1)

GMALL-Isatuximab

EXPERIMENTAL

Cohort 1: In this Cohort, Isatuximab shall be implemented as part of a combination therapy for patients with R/R T-ALL/T-LBL, defined as bone marrow infiltration of ≥5% (R/R T-ALL) or ≥1% minimal residual disease (MRD). Cohort 2: In this Cohort, Isatuximab shall be implemented as single drug treatment for patients with molecular failure/relapse. Cohort 2 will include patients with hematologic remission (bone marrow blast count \<5%) of T-cell ALL, but with molecular failure or molecular relapse (MRD+ T-ALL) - terminated with protocol version 3.2.

Drug: Isatuximab

Interventions

Isatuximab DRUG

Cohort 1: All patients will receive two cycles of induction therapy with standard chemotherapy, Bortezomib and Isatuximab. Isatuximab maintenance may be administered in patients with CR until SCT, progression/relapse, unacceptable toxicity, physicians' decision to change treatment or withdrawal of consent.

Also known as: Bortezomib

GMALL-Isatuximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Cohort 1:
• Patients with CD38 positive T-ALL/T-LBL
• Either: In relapse or with primary refractory disease defined as ≥5% blasts in bone marrow cytology or ≥1% minimal residual disease (MRD)
• Or: Extramedullary relapse or primary refractory disease confirmed by standard imaging with measurable target leasions
• after at least three chemotherapy cycles (induction I-II, consolidation I) with the following additional specifications:
• early relapse within 12 months from first achievement of CR or
• late relapse later than 12 months from first achievement of CR or
• primary refractory disease without any CR or
• any relapse after stem cell transplantation or
• any refractory relapse, defined as no response to at least one salvage therapy or
• any second or later relapse and
• Availability of patient material with blast cells (bone marrow or peripheral blood) for central MRD assessment or availability of respective predefined marker (not required in patients with extramedullary disease only).
• ECOG status: 0-2
• Age ≥ 18 years
• Evidence of a personally signed and dated informed consent indicating that the patient has been informed of all pertinent aspects of the study

You may not qualify if:

• Cohort 1:
• Patients with CNS-only relapse
• Patients who have received prior antileukemic immunotherapy within 2 weeks prior to start of Isatuximab treatment
• Patients who have received treatment for leukemia with chemotherapy as follows:
• Patients who have received treatment for leukemia with chemotherapy within 2 weeks prior to start of Isatuximab treatment (exception: documented disease progression under chemotherapy and pre-phase therapy with 5-7 days of Dexamethasone, 3 days of Cyclophosphamide; intrathecal prophylaxis)
• Patients who are candidates for a treatment with Nelarabine (eligibility to be assessed particularly in patients with extramedullary involvement and/or early/mature T-ALL/T-LBL, due to limited efficacy)
• Patients must have recovered from acute non-hematologic toxicity form previous therapies to ≤ grade I unless signs or symptoms are correlated to leukaemia involvement
• Prior SCT ≤ 3 months from start of study treatment
• Acute GvHD ≥ grade II or active chronic GvHD requiring systemic treatment
• Any systemic GvHD prophylaxis or treatment within 2 weeks from start of study treatment
• Known HIV positivity, known hepatitis B surface antigen positivity or known history of hepatitis C
• Unstable or severe uncontrolled medical condition e.g. unstable cardiac function or unstable pulmonary condition
• Treatment with an investigational agent within 4 weeks from start of study treatment (safety follow-up period of respective study)
• Concurrent active malignancy other than non-melanoma skin cancer, carcinoma in situ of the cervix, or localized prostate cancer that has been treated with radiation or surgery; patients with previous malignancies are eligible if they have been disease free for ≥ 2 years and do not require any antitumor therapy
• Evidence of uncontrolled current serious active infection or recent history (within 4 months) of deep tissue infections such as fasciitis or osteomyelitis

Sponsors & Collaborators

• Goethe University: lead
• Sanofi: collaborator

Study Sites (15)

University Hospital Augsburg, II. Medizinischen Klinik, Hämatologie, internistische Onkologie und Hämostaseologie

Augsburg, 86156, Germany

RECRUITING

Charité Berlin, Campus Benjamin Franklin, Department of Hematology, Oncology and Tumorimmunologyt Hämatologie

Berlin, 12203, Germany

RECRUITING

Gesundheit Nord Klinikverbund Bremen gGmbH, Klinikum Bremen-Mitte, Med. Klinik I

Bremen, 28205, Germany

RECRUITING

Klinikum Carl Gustav Carus Dresden, Medizinische Klinik und Poliklinik I

Dresden, 01307, Germany

RECRUITING

University Hospital Düsseldorf, Department of Hematology, Oncology and Clinical Immunology

Düsseldorf, 40225, Germany

RECRUITING

University Hospital Erlangen AöR, Department of Medicine 5

Erlangen, 91054, Germany

RECRUITING

Goethe University Hospital Frankfurt, Department of Medicine, Hematology and Oncology

Frankfurt am Main, 60580, Germany

RECRUITING

University Hospital Hamburg-Eppendorf, Department of Medicine II

Hamburg, 20251, Germany

RECRUITING

University Hospital Heidelberg, Department V, Hematology, Oncology and Rheumatology

Heidelberg, 69120, Germany

RECRUITING

University Hospital Schleswig-Holstein, Campus Kiel, Medical Department II

Kiel, 24105, Germany

RECRUITING

University Hospital Leipzig; Klinik für Hämatologie, Zelltherapie, Hämostaseologie und Infektiologie, Bereich Hämatologie und Zelltherapie

Leipzig, 04103, Germany

RECRUITING

University Hospital München-Großhadern, Medizinische Klinik und Poliklinik III

München, 81377, Germany

RECRUITING

University Hospital Münster, Medizinische Klinik A / KMT-Zentrum

Münster, 48149, Germany

RECRUITING

Klinikum Oldenburg AöR, Universitätsklinik für Innere Medizin - Onkologie und Hämatologie

Oldenburg, 26135, Germany

RECRUITING

Robert-Bosch-Krankenhaus; Abteilung für Hämatologie, Onkologie und Palliativmedizin

Stuttgart, 70376, Germany

RECRUITING

MeSH Terms

Conditions

Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

Interventions

isatuximab; Bortezomib

Condition Hierarchy (Ancestors)

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Nicola Goekbuget, MD

  Department of Medicine, Hematology and Oncology, Goethe University Frankfurt, Frankfurt, Germany

  STUDY DIRECTOR

• Anjali Cremer, MD

  Department of Medicine, Hematology and Oncology, Goethe University Frankfurt, Frankfurt, Germany

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nicola Goekbuget, MD

CONTACT

0049-6963016365; goekbuget@em.uni-frankfurt.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. Nicola Gökbuget, Head of Trial Center

Study Record Dates

• First Submitted: July 15, 2024
• First Posted: October 18, 2024
• Study Start: October 22, 2024
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2030
• Last Updated: August 28, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (15)