Allogeneic Donor Lymphocyte Infusions Combined With Blinatumomab

NCT03982992 | Withdrawn Phase 2 DMC

• 1 other identifier: 2017-002314-31
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This phase 2 study is designed to evaluate the safety, tolerability and efficacy of allogeneic donor lymphocyte infusions (DLI) combined with the bispecific T cell engager blinatumomab in B-precursor ALL patients who have mixed chimerism (MC) or are MRD-positive after allogeneic SCT and are refractory to at least one MRD- or MC-targeted therapy (i.e. blinatumomab, DLI, tyrosine kinase inhibitors or other agents).

Conditions

B Cell Precursor Acute Lymphoblastic Leukemia With Mixed Chimerism or Minimal Residual Disease After Allogeneic Stem Cell Transplantation; B-Cell Acute Lymphoblastic Leukemia; Acute Lymphoblastic Leukemia; Acute Lymphoblastic Leukemia in Remission; Acute Lymphoblastic Leukemia, Adult

Keywords

donor lymphocyte infusion; blinatumomab; combinatorial; minimal residual disease; MRD; mixed chimerism; MC; DLI-TARGET; acute lymphoblastic leukemia

Outcome Measures

Primary Outcomes (1)

• 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

  Subject incidence and grade of adverse events (AEs) including graft-versus-host disease (GvHD). The intensity of (S)AEs will be assessed according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.03.

  18 weeks

Secondary Outcomes (2)

• Efficacy of a combined treatment of DLI and blinatumomab to induce a complete MRD/chimerism response

  18 weeks

• Duration of the response and survival after combined treatment of DLI and blinatumomab

  18 weeks

Study Arms (1)

DLI-TARGET

EXPERIMENTAL

14d screening period: methotrexate, cytarabine, dexamethasone infusion i.th. Cycle 1 (all patients): d1-28: blinatumomab continuous infusion i.v., d4: allogeneic donor lymphocyte single infusion i.v., d29: methotrexate, cytarabine, dexamethasone infusion i.th. Cycle 2 (only patients with toxicity ≤ grade 2 CTCAE in cycle 1): d43-d70: blinatumomab continuous infusion i.v., d46: allogeneic donor lymphocyte single infusion i.v., d71: methotrexate, cytarabine, dexamethasone infusion i.th.

Drug: Blinatumomab in combination with donor lymphocyte infusion

Interventions

Blinatumomab in combination with donor lymphocyte infusion DRUG

Continuous blinatumomab infusion in combination with allogeneic donor lymphocyte infusion

DLI-TARGET

Eligibility Criteria

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

You may qualify if:

• Adult 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.
• 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.
• 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.
• 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.
• Availability of allogeneic donor lymphocytes from the subject's donor (at least 2 x 10\^8 T cells/kg).
• Subject has provided written informed consent prior to initiation of any study-specific activities/procedures.
• Subject has provided informed consent to be followed up in the GMALL-Registry.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.
• Renal function as follows: serum creatinine \< 2.0 mg/dL and estimated glomerular filtration rate \> 30 mL/min.
• 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)

You may not qualify if:

• Eligibility for treatment with blinatumomab ALONE or other antibody-based treatment approaches (e.g. inotuzumab ozogamicin), as considered by the treating physician.
• Eligibility for standard chemotherapy, as considered by the treating physician.
• 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.
• Treatment with systemic immune modulators including, but not limited to, non-topical systemic corticosteroids, cyclosporine, and tacrolimus within 2 weeks before enrollment.
• Any grade of GvHD currently requiring treatment.
• Clinically relevant central nervous system (CNS) pathology requiring treatment (e.g., unstable epilepsy).
• Evidence of current CNS involvement by ALL.

Sponsors & Collaborators

• Ludwig-Maximilians - University of Munich: lead
• Amgen: collaborator

Study Sites (1)

Klinikum der Universität München

Munich, 81377, Germany

Location

MeSH Terms

Conditions

Burkitt Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Neoplasm, Residual

Interventions

blinatumomab

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Marion Subklewe, MD

  Klinikum der Universität München

  PRINCIPAL INVESTIGATOR

• Christian Schmidt, MD

  Klinikum der Universität München

  PRINCIPAL INVESTIGATOR

• Sascha Haubner, MD

  Klinikum der Universität München

  PRINCIPAL INVESTIGATOR

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: Deputy Principal Investigator

Study Record Dates

• First Submitted: June 3, 2019
• First Posted: June 12, 2019
• Study Start: June 1, 2019
• Primary Completion: May 31, 2021
• Study Completion: November 30, 2021
• Last Updated: March 12, 2024

Record last verified: 2024-03

Locations

DE (1)