Clinical trial NCT02187354: Expanded Access Protocol - Blinatumomab in Pediatric & Adolescent Subjects With Relapsed/Refractory B-precursor ALL
Official title: An Open-Label, Multi-center, Expanded Access Protocol of Blinatumomab for the Treatment of Pediatric and Adolescent Subjects With Relapsed and/or Refractory B-precursor Acute Lymphoblastic Leukemia (ALL)
Study type: EXPANDED_ACCESS
Overall status: NO_LONGER_AVAILABLE
Conditions: Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2014-07-11
Sex: ALL
Minimum age (years): 0
Maximum age (years): 17
Standard ages: CHILD

Brief summary: Primary Objective:

To estimate the incidence of treatment-emergent and treatment-related adverse events during treatment with blinatumomab in pediatric and adolescent subjects with B-precursor ALL in second or later bone marrow relapse, in any marrow relapse after alloHSCT, or refractory to other treatments

Secondary Objective(s):

To describe key efficacy outcomes, including incidence of complete response (CR) within 2 cycles of blinatumomab, minimal residual disease (MRD) remission within 2 cycles of blinatumomab, relapse free survival (RFS), overall survival (OS), incidence of alloHSCT, and 100-day mortality after alloHSCT.

Hypotheses:

A formal statistical hypothesis will not be tested. The incidence of treatment-emergent and treatment-related adverse events will be estimated.

Study Endpoints:

* Incidence of treatment-emergent and treatment-related adverse events
* Incidence of CR within 2 cycles of blinatumomab
* MRD remission within 2 cycles of blinatumomab
* RFS
* OS
* Incidence of alloHSCT
* 100-day mortality after alloHSCT

Study Design:

Multi-center, open-label, single-arm expanded access protocol


Eligibility criteria: Inclusion Criteria 101 Immunophenotypic evidence of CD19 positive B-precursor ALL (pro B-, pre B-, common ALL) 102 Age \> 28 days and \< 18 years at the time of informed consent/assent 103 Morphological or molecular evidence of relapsed/refractory disease, defined as one of the following:

* Second or later bone marrow relapse (defined as M3 marrow or M2 marrow or M1 marrow but with MRD level ≥ 10E-3), or
* Any marrow relapse after alloHSCT (defined as M3 marrow or M2 marrow or M1 marrow but with and MRD level ≥ 10E-3), or
* Refractory to other treatments:

  * For patients in first relapse: failure to achieve a CR following a full standard reinduction chemotherapy regimen
  * For patients who have not achieved a first remission: failure to achieve remission following a full standard induction regimen
* Subjects previously treated with blinatumomab may be eligible, if subject ended treatment for reason(s) other than disease progression or intolerability to blinatumomab (Note: This does not include patients who have already received blinatumomab treatment on this study, but refers only to patients outside of the 20130320 study)

Other Inclusion Criteria may apply

Exclusion Criteria 201 Any active acute Graft-versus-Host Disease (GvHD) grade 2 to grade 4 according to the Glucksberg criteria or active chronic GvHD requiring systemic treatment 202 Immunosuppresive agents to prevent or treat GvHD within 2 weeks prior to blinatumomab treatment (except for topical corticosteroids) 203 Active (overt) ALL in the CNS (confirmed by cerebrospinal fluid \[CSF\] analysis) or in testes

Other Exclusion Criteria may apply

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Research Site
state: Colorado
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Memphis
country: United States
facility: Research Site
state: Tennessee
city: Salt Lake City
country: United States
facility: Research Site
state: Utah
city: Wien
country: Austria
facility: Research Site
city: Marseille cedex 5
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Frankfurt am Main
country: Germany
facility: Research Site
city: Kiel
country: Germany
facility: Research Site
city: München
country: Germany
facility: Research Site
city: Münster
country: Germany
facility: Research Site
city: Tübingen
country: Germany
facility: Research Site
city: Würzburg
country: Germany
facility: Research Site
city: Monza (MB)
country: Italy
facility: Research Site
city: Padova
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Zuerich
country: Switzerland
facility: Research Site
city: Sheffield
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Locatelli F, Zugmaier G, Mergen N, Bader P, Jeha S, Schlegel PG, Bourquin JP, Handgretinger R, Brethon B, Rossig C, Kormany WN, Viswagnachar P, Chen-Santel C. Blinatumomab in pediatric relapsed/refractory B-cell acute lymphoblastic leukemia: RIALTO expanded access study final analysis. Blood Adv. 2022 Feb 8;6(3):1004-1014. doi: 10.1182/bloodadvances.2021005579.
citation: Locatelli F, Zugmaier G, Mergen N, Bader P, Jeha S, Schlegel PG, Bourquin JP, Handgretinger R, Brethon B, Rossig C, Chen-Santel C. Blinatumomab in pediatric patients with relapsed/refractory acute lymphoblastic leukemia: results of the RIALTO trial, an expanded access study. Blood Cancer J. 2020 Jul 24;10(7):77. doi: 10.1038/s41408-020-00342-x. No abstract available.
citation: Queudeville M, Stein AS, Locatelli F, Ebinger M, Handgretinger R, Gokbuget N, Gore L, Zeng Y, Gokani P, Zugmaier G, Kantarjian HM. Low leukemia burden improves blinatumomab efficacy in patients with relapsed/refractory B-cell acute lymphoblastic leukemia. Cancer. 2023 May 1;129(9):1384-1393. doi: 10.1002/cncr.34667. Epub 2023 Feb 24.