Phase 1b/2 Study of Carfilzomib in Combination with Dexamethasone, Mitoxantrone, PEG-asparaginase, and Vincristine (UK R3 Induction Backbone) in Children with Relapsed or Refractory Acute Lymphoblastic Leukemia

Phase 1

• Conditions: Relapsed or Refractory Acute Lymphoblastic Leukemia; MedDRA version: 18.0Level: LLTClassification code 10025230Term: Lymphatic leukemiaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-001633-84-ES
• Lead Sponsor: Onyx Therapeutics, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-01-26
• Last Update Posted: 2 October 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 39

Inclusion Criteria

1. Age 18 years or younger at the time of study treatment initiation.
2. Subjects must have a diagnosis of relapsed (Phase 1b and 2) or refractory (Phase 1b only) ALL with ? 5% blasts in the bone marrow (M2 or M3 disease), with or without extramedullary disease.
?- To be eligible for Phase 1b, subjects must have had 1 or more prior
therapeutic attempts, defined as:
o Early first relapse (< 36 months from original diagnosis) after
achieving a CR OR
o Relapse after achieving a CR following the first or subsequent relapse
(i.e., ? 2 relapses) OR
o Failing to achieve a CR from original diagnosis after at least 1 induction attempt
?- To be eligible for Phase 2, subjects must have had 2 or more prior
therapeutic attempts and have relapsed, but not refractory disease, defined as relapse after achieving a CR following the first or subsequent relapse (i.e., ? 2 relapses)
3. Subjects must have fully recovered from the acute toxic effects of all previous chemotherapy, immunotherapy, or radiotherapy treatment before enrollment.
4. Subjects must have a serum creatinine level that is ? 1.5 × institutional upper limit of normal (ULN) according to age. If serum creatinine level is > 1.5 × ULN, the subject must have a calculated creatinine clearance or radioisotope glomerular filtration rate (GFR) ? 70 mL/min/1.73 m2.
5. Adequate liver function, defined as both of the following:
? Total bilirubin ? 1.5 × institutional ULN
? AST and ALT ? 5 × institutional ULN
6. Performance status: Karnofsky or Lansky scores ? 50 for subjects > 16 years old or ? 16 years old, respectively.
Are the trial subjects under 18? yes
Number of subjects for this age range: 39
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Known allergy to any of the drugs used in the study. (Subjects who have had a previous allergy to PEG-asparaginase but can receive
Erwinia are eligible.)
2. Known allergy to Captisol (a cyclodextrin derivative used to solubilize
carfilzomib; for a complete listing of Captisol-enabled drugs, see the Ligand Pharmaceuticals, Inc. website)
3. Left ventricular fractional shortening < 30%
4. History of pancreatitis; serum amylase > 2 × the institutional ULN
5. Active treatment for graft-versus-host disease
6. Positive culture for bacteria or fungus within 14 days of the initiation of therapy
7. Down Syndrome
8. Prior therapy restrictions:
? -Subjects must have completed therapy with granulocyte-colony stimulating factor (G-CSF) or other myeloid growth factors at least 7 days before enrollment, or at least 14 days before enrollment, if pegylated myeloid growth factors were administered.
? -Subjects must have received the last dose of a non-monoclonal antibody biologic agent at least 7 days before enrollment. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be approved by the Onyx study medical monitor.
? -At least 3 antibody half-lives must have elapsed since the last dose of monoclonal antibody (i.e., 66 days for rituximab and 69 days for
epratuzumab) before subjects may enroll in the study.
? -Subjects must have completed any type of active immunotherapy
(e.g., tumor vaccines) at least 42 days before enrollment.
? -Subjects must not have received any other antineoplastic agents within 7 days prior to enrollment.

Study & Design

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