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

NCT ID: NCT06648889

Last Updated: 2026-01-15

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-10-22
• Study Completion Date: 2028-08-31

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

GMALL-Isatuximab

Cohort 1: In this Cohort, Isatuximab shall be implemented as part of a combination therapy for patients with R/R T-ALL, defined as bone marrow infiltration of ≥5% (R/R T-ALL).

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).

Group Type: EXPERIMENTAL

Isatuximab

Intervention Type: 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.

Isatuximab

Intervention Type: DRUG

Cohort 2: All patients will receive at least one cycle with Isatuximab. Each cycle will be 4 weeks in duration. Isatuximab will be administered until SCT, hematologic relapse including extramedullary, unacceptable toxicity, physicians' decision, or withdrawal of consent.

Interventions

Isatuximab

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.

Intervention Type: DRUG

Isatuximab

Cohort 2: All patients will receive at least one cycle with Isatuximab. Each cycle will be 4 weeks in duration. Isatuximab will be administered until SCT, hematologic relapse including extramedullary, unacceptable toxicity, physicians' decision, or withdrawal of consent.

Intervention Type: DRUG

Other Intervention Names

Bortezomib

Eligibility Criteria

Inclusion Criteria

• Patients with CD38 positive T-ALL fitting either to the definitions for cohort 1 or cohort 2:

Cohort 1: In relapse or with primary refractory disease defined as ≥5% blasts in bone marrow 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.

Cohort 2: In complete hematological remission (defined as less than 5% blasts in bone marrow and no evidence of extramedullary disease) after at least three chemotherapy cycles (induction I-II, consolidation I)

• Detection of quantifiable MRD at a level of ≥10-4, either as molecular failure without prior achievement of molecular remission or molecular relapse after prior achievement of molecular remission
• MRD assay at the central reference lab with at least one marker a minimum sensitivity of 10-4
• MRD detection for study inclusion after an interval of at least 2 weeks from last systemic chemotherapy including antibody therapy
• (in patients without clonal molecular MRD marker, MRD testing can be based on flow-cytometry established in reference laboratory)

ECOG status:

• Cohort 1: 0-2
• Cohort 2: 0-1

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 Patient must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures

Regeneration from last chemotherapy defined as follows:

Cohort 1:

• Platelets ≥10.000/uL (platelet transfusion allowed)
• Hemoglobin ≥ 7.5 g/dl (red blood cell transfusion allowed)

Cohort 2:

• Neutrophils ≥1.000/uL
• Platelets ≥50.000/uL
• Hemoglobin ≥9 g/dl

Adequate liver function defined as follows:

• Bilirubin ≤ 1.5 ULN (unless Gilbert Meulengracht disease or classified as result of liver infiltration by investigator)
• AST and ALT ≤ 2.5 x ULN (unless classified as result of liver infiltration by investigator)

Adequate renal function defined as follows:

• Serum creatinine ≤ 2 x ULN
• Any serum creatinine level associated with a calculated creatinine clearance ≤ 40 mL/min
• Negative pregnancy test in women of childbearing potential (WOCBP)
• WOCBP must commit to either abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control simultaneously.
• Men who are sexually active with a WOCBP must agree to use a barrier method of contraception
• Participation in the registry of the German Multicenter Study Group for Adult ALL (GMALL)

Exclusion Criteria

• Extramedullary involvement except for non-bulky (<7.5 cm) lymph node involvement, splenomegaly, or hepatomegaly
• 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:

Cohort 1:

• Patients who have received treatment for leukemia with chemotherapy within 2 weeks prior to start of Isatuximab treatment (exception: pre-phase therapy with 5-7 days of Dexamethasone, 3 days of Cyclophosphamide; intrathecal prophylaxis)
• Patients who are candidates for a treatment with Nelarabine

Cohort 2:

• Any chemotherapy or antibody therapy after the MRD assay leading to study inclusion (exception: intrathecal prophylaxis)
• Patients must have recovered from acute non-hematologic toxicity from previous therapies to ≤ grade I unless signs or symptoms are correlated to leukemia 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
• Known allergies, hypersensitivity, or intolerance to boron or Mannitol, corticosteroids, mAb (including Isatuximab) or human proteins, or their excipients (refer to respective Summary of Product Characteristics), or known sensitivity to mammalian-derived products.
• Active infection, any other concurrent disease or medical condition that are deemed to interfere with the conduct of the study as judged by the investigator
• Pregnant or breastfeeding females
• Vaccination with live attenuated vaccines within 4 weeks of first study agent administration.
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgement of the investigator, would make the patient inappropriate for entry into this study

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: collaborator

Goethe University

OTHER

Sponsor Role: lead

Responsible Party

Nicola Goekbuget

Dr. Nicola Gökbuget, Head of Trial Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Nicola Goekbuget, MD

Role: STUDY_DIRECTOR

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

Anjali Cremer, MD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

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

Augsburg, , Germany

Site Status: RECRUITING

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

Berlin, , Germany

Site Status: RECRUITING

Klinikum Carl Gustav Carus Dresden, Medizinische Klinik und Poliklinik I

Dresden, , Germany

Site Status: RECRUITING

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

Düsseldorf, , Germany

Site Status: RECRUITING

University Hospital Erlangen AöR, Department of Medicine 5

Erlangen, , Germany

Site Status: RECRUITING

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

Frankfurt am Main, , Germany

Site Status: RECRUITING

University Hospital Hamburg-Eppendorf, Department of Medicine II

Hamburg, , Germany

Site Status: RECRUITING

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

Heidelberg, , Germany

Site Status: RECRUITING

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

Kiel, , Germany

Site Status: RECRUITING

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

Leipzig, , Germany

Site Status: RECRUITING

University Hospital München-Großhadern, Medizinische Klinik und Poliklinik III

München, , Germany

Site Status: RECRUITING

University Hospital Münster, Medizinische Klinik A / KMT-Zentrum

Münster, , Germany

Site Status: RECRUITING

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

Oldenburg, , Germany

Site Status: RECRUITING

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

Stuttgart, , Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Nicola Goekbuget, MD

Role: CONTACT

goekbuget@em.uni-frankfurt.de

0049-6963016365

Facility Contacts

Andreas Rank, MD

Role: primary

Stefan Schwartz, MD

Role: primary

Lisa Heberling, MD

Role: primary

Kathrin Nachtkamp, MD

Role: primary

Bernd Spriewald, MD

Role: primary

Nicola Goekbuget, MD

Role: primary

goekbuget@em.uni-frankfurt.de

0049-6963016365

Walter Fiedler, MD

Role: primary

Simon Raffel, MD

Role: primary

Lars Fransecky, MD

Role: primary

Georg-Nikolaus Franke, MD

Role: primary

Veit Bücklein, MD

Role: primary

Matthias Stelljes, MD

Role: primary

Andreas Voß, MD

Role: primary

Sonja Martin, MD

Role: primary

Other Identifiers

2023-507899-47-00

Identifier Type: CTIS

Identifier Source: secondary_id

GMALL-Isatuximab

Identifier Type: -

Identifier Source: org_study_id