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.
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 - terminated with protocol version 3.2.
Study 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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
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
* 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:
* Platelets ≥10.000/uL (platelet transfusion allowed)
* Hemoglobin ≥ 7.5 g/dl (red blood cell transfusion allowed)
* 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)
Cohort 2:
• terminated with protocol version 3.2.
Exclusion Criteria:
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
* 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
Cohort 2:
• terminated with protocol version 3.2.
Primary outcome measure(s)
Proportion of patients with complete hematologic response (ORR= CR and CRi) — Day 22, Week 9, per SoC Cohort 1: Proportion of patients with complete hematologic response (ORR= CR and CRi) after 2 cycles of induction therapy including Isatuximab.
Overall incidence and severity of adverse events — Day 22, Week 9, month 3, month 6 (depends on duration of therapy which is variable) Cohort 1: Overall incidence and severity of adverse events (CTCAE 5.0).
Proportion of patients with molecular response (MolCR) — Day 22, Week 9, per SoC Cohort 2:
Proportion of patients with molecular response (MolCR) after one cycle of Isatuximab.
Trial sites (15)
Facility
City
Region
Status
University Hospital Augsburg, II. Medizinischen Klinik, Hämatologie, internistische Onkologie und Hämostaseologie
Augsburg
Germany
Recruiting
Charité Berlin, Campus Benjamin Franklin, Department of Hematology, Oncology and Tumorimmunologyt Hämatologie
Berlin
Germany
Recruiting
Gesundheit Nord Klinikverbund Bremen gGmbH, Klinikum Bremen-Mitte, Med. Klinik I
Bremen
Germany
Recruiting
Klinikum Carl Gustav Carus Dresden, Medizinische Klinik und Poliklinik I
Dresden
Germany
Recruiting
University Hospital Düsseldorf, Department of Hematology, Oncology and Clinical Immunology
Düsseldorf
Germany
Recruiting
University Hospital Erlangen AöR, Department of Medicine 5
Erlangen
Germany
Recruiting
Goethe University Hospital Frankfurt, Department of Medicine, Hematology and Oncology
Frankfurt am Main
Germany
Recruiting
University Hospital Hamburg-Eppendorf, Department of Medicine II
Hamburg
Germany
Recruiting
University Hospital Heidelberg, Department V, Hematology, Oncology and Rheumatology
Heidelberg
Germany
Recruiting
University Hospital Schleswig-Holstein, Campus Kiel, Medical Department II
Kiel
Germany
Recruiting
University Hospital Leipzig; Klinik für Hämatologie, Zelltherapie, Hämostaseologie und Infektiologie, Bereich Hämatologie und Zelltherapie
Leipzig
Germany
Recruiting
University Hospital München-Großhadern, Medizinische Klinik und Poliklinik III
München
Germany
Recruiting
University Hospital Münster, Medizinische Klinik A / KMT-Zentrum
Münster
Germany
Recruiting
Klinikum Oldenburg AöR, Universitätsklinik für Innere Medizin - Onkologie und Hämatologie
Oldenburg
Germany
Recruiting
Robert-Bosch-Krankenhaus; Abteilung für Hämatologie, Onkologie und Palliativmedizin
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
We use cookies to analyse site traffic and improve your experience. With your consent, we may also use cookies for advertising. You can change your choice at any time.