Allogeneic Donor Lymphocyte Infusions Combined with Blinatumomab

Phase 1

• Conditions: Subjects with treatment-resistant mixed chimerism or MRD of CD19+ B-precursor ALL after allogeneic SCT; MedDRA version: 20.0Level: LLTClassification code 10063621Term: Acute lymphoblastic leukaemia recurrentSystem Organ Class: 100000004864; MedDRA version: 20.0Level: LLTClassification code 10063625Term: Acute lymphoblastic leukemia recurrentSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2017-002314-31-DE
• Lead Sponsor: Klinikum der Universität München

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-05-03
• Last Update Posted: 20 July 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

1)Patients with CD19+ B–precursor ALL (as determined by immunophenotyping) in hCR (defined as having less than 5% blasts in bone marrow) after allogeneic SCT.
2)One, or a combination of the following documented after an interval of at least 2 weeks since cessation of the most recent leukemia-targeting therapy (i.e. chemotherapy, immunotherapy or cellular therapy, except for intrathecal prophylaxis):
-Positivity for CD19+ MRD (molecular failure or molecular relapse), defined as presence of MRD at a level of =10-4 according to an assay with a minimum sensitivity of 10-4.
-Donor chimerism <90%, as determined by analysis of host and donor STRs in bone marrow sample engraftment analysis.
3)At least one previous line of treatment for MRD-positivity and/or reduced donor chimerism (i.e. blinatumomab, DLI, TKI or other agents) after allogeneic SCT.
4)For those with BCR/ABL-positive B-precursor ALL only: persistence of MRD and/or MC following at least one = second generation TKI (dasatinib, nilotinib, bosutinib, ponatinib) OR intolerance to second generation TKI and intolerance to or persistence of MRD and/or MC following imatinib mesylate.
5)Availability of allogeneic donor lymphocytes from the subject’s donor (at least 2 x 108 T cells/kg).
6)Subject (or subject's legally acceptable representative when the subject is legally too young to provide informed consent) has provided written informed consent prior to initiation of any study-specific activities/procedures.
7)Subject (or Subject’s legally acceptable representative when the subject is legally too young to provide informed consent) has provided informed consent to be followed up in the GMALL-Registry.
8)Eastern Cooperative Oncology Group (ECOG) Performance Status of = 2.
9)Renal function as follows: serum creatinine < 2.0 mg/dL and estimated glomerular filtration rate > 30 mL/min.
10)Hepatic function as follows:
-Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) = 3.0 x upper limit of normal (ULN)
-Alkaline phosphatase (ALP) < 3.0 x ULN
-Bilirubin = 2.0 x ULN (unless considered due to Gilbert's syndrome or hemolysis)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2

Exclusion Criteria

1)Eligibility for treatment with blinatumomab ALONE or other antibody-based treatment approaches (e.g. inotuzumab ozogamicin), as considered by the treating physician.
2)Eligibility for standard chemotherapy, as considered by the treating physician.
3)Antitumor therapy (chemotherapy, antibody therapy, molecular-targeted therapy, retinoid therapy, or investigational agent) within 14 days or 5 half-lives (whichever is longer) prior to baseline MRD and/or chimerism assessment.
4)Treatment with systemic immune modulators including, but not limited to, non-topical systemic corticosteroids, cyclosporine, and tacrolimus within 2 weeks before enrollment.
5)Any grade of GvHD currently requiring treatment.
6)Clinically relevant central nervous system (CNS) pathology requiring treatment (e.g., unstable epilepsy).
7)Evidence of current CNS involvement by ALL. Subjects with CNS relapse at the time of relapse are eligible if CNS is successfully controlled prior to enrollment.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the safety and tolerability of combined DLI and blinatumomab treatment in subjects with treatment-resistant MC or MRD of CD19+ B-precursor ALL after allogeneic SCT.;Secondary Objective: 1)To evaluate the efficacy of a combined treatment of DLI and blinatumomab to induce a complete MRD/chimerism response. <br>2)To evaluate the duration of the response and survival<br>;Primary end point(s): Subject incidence and grade of AEs including GvHD;Timepoint(s) of evaluation of this end point: Safety in terms of AE incidence will be evaluated after the first patient received at least one dose with blinatumomab until LVLS.