Phase 1b/2 Study of Carfilzomib in Combination with Induction Chemotherapy in Children with Relapsed or Refractory Acute Lymphoblastic Leukemia

Phase 1

• Conditions: Relapsed or Refractory Acute Lymphoblastic Leukemia; MedDRA version: 21.0Level: LLTClassification code 10025230Term: Lymphatic leukemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-001633-84-BG
• Lead Sponsor: Onyx Therapeutics, Inc., an Amgen Inc. subsidiary

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-04-01
• Last Update Posted: 5 August 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 144

Inclusion Criteria

110 Subject’s legally acceptable representative has provided informed consent when the subject is legally too young to provide informed consent and the subject has provided written assent based on local regulations and/or guidelines prior to any study-specific activities/procedures being initiated, except for standard care local testing as permitted per Section 21.3.
111 Age greater than or equal to 1 month to less than 21 years. Subjects greater than or equal to 18 years must have had their original diagnosis at at less than 18 years of age
112 Subjects must be diagnosed with relapsed or refractory relapsed ALL.
113 Subjects must have a documented first remission, less than 5% blasts in the bone marrow (M1 bone marrow) and no evidence of extramedullary disease.
114 T-cell ALL with bone marrow relapse (defined as greater than or equal
to 5% leukemia blasts in bone marrow) or refractory relapse with or without extramedullary disease.
OR
B-cell ALL with bone marrow relapse or refractory relapse (defined as greater than or equal
to 5% leukemia blasts in bone marrow) after having received a targeted B-cell immune therapy as treatment for a prior relapse (eg, blinatumomab, inotuzumab or a CAR-T therapy) with or without extramedullary disease.
115 Adequate liver function: bilirubin less than or equal to 1.5 x upper limit of normal (ULN), alanine aminotransferase (ALT) less than or equal to 5 x ULN.
116 Adequate renal function: serum creatinine less than or equal to 1.5 x
ULN or glomerular filtration rate (GFR) greater than or equal to 70 mL/min/1.73 m2; or for children less than 2 years of age, greater than or equal to 50 mL/min/1.73 m2.
117 Adequate cardiac function: shortening fraction greater than or equal to 30% or ejection fraction greater than or equal to 50%.
118 Karnofsky (subjects greater than or equal to 16 years of age) or Lansky (subjects 12 months to less than 16 years of age) performance status greater than or equal to 50%.
119 Subjects must have fully recovered from the acute toxic effects of all
previous chemotherapy, immunotherapy, or radiotherapy treatment
before enrolment (for example: recovery from gastrointestinal toxicity
may occur more rapidly than less reversible organ toxicities such as sinusoidal obstruction syndrome or non-infectious pneumonitis, for serious prior toxicities recommend discussion with Amgen medical monitor).
120 Life expectancy of greater than 6 weeks per investigator`s judgment at time of screening.
Are the trial subjects under 18? yes
Number of subjects for this age range: 144
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) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

211 Prior treatment with carfilzomib.
214 Intolerance, hypersensitivity, or inability to receive any of the chemotherapy components of the VXLD regimen (or acceptable substitutes as listed in the protocol). An exception is allowed for allergy to asparaginase products if Erwinia asparaginase is unable to be administered.
215 Autologous HSCT within 6 weeks prior to start of study treatment.
216 Allogeneic HSCT within 3 months prior to start of study treatment.
217 Active GVHD requiring systemic immune suppression.
218 < 30 days from discontinuation of immune suppressive therapy
administered for the treatment of acute or chronic GVHD.
219 Isolated extramedullary relapse.
220 Positive bacterial or fungal infection within 14 days of enrolment (except for documented line infection, line has been removed, and blood culture after line removal is negative for 5 days prior to first dose of induction therapy). Antibiotics may be administered for prophylaxis as per institutional standards up to and after enrollment.
221 Subjects with < 3 antibody half-lives since the last dose of monoclonal antibody, prior to first dose of investigational product must be discussed with the Amgen medical monitor and may be allowed to
enroll based on extent of disease or evidence of rapidly rising peripheral
or bone marrow blast counts.
222 Cell-based immunotherapy within 42 days prior to first dose of
investigational product. If the Amgen medical monitor agrees, an exception may be granted to the 42-day requirement for subjects with rapidly rising peripheral or bone marrow blast counts.
223 Down's syndrome.
224 Presence of another active cancer.
225 History of grade greater than or equal to 2 pancreatitis within 6
months to screening
226 Unresolved toxicities from prior anticancer therapy, defined as not
having resolved to CTCAE version 4.03 grade 1 or to levels dictated in the eligibility criteria apart from alopecia or toxicities from prior anticancer therapy that are considered irreversible and do not trigger another exclusion criterion (defined as having been present and stable
for greater than 4 weeks)
227 Antitumor therapy within 7 days of day 1 of induction. Exception:
hydroxyurea to control peripheral blood leukemic cell counts is allowed
until start of investigational product.
228 Active viral infection, including but not limited to CMV, Hepatitis B
with positive serum hepatitis surface antigen or hepatitis B DNA, HIV,
Hepatitis C with detectable hepatitis C RNA. Subjects who have previously received a stem cell transplant must be screened for CMV
infection, unless both subject and donor are known to be CMV negative.
229 Currently receiving treatment in another investigational device or
product study, or less than 14 days since ending treatment on another
investigational device or product study.
230 Uncontrolled arrhythmias or screening ECG with corrected QTc >470 msec.
231 History or evidence of any other clinically significant disorder,
condition or disease that, in the opinion of the investigator or Amgen
physician, if consulted, would pose a risk to subject safety or interfere
with the study evaluation, procedures or completion.
232 Female subject is pregnant/breastfeeding or planning to become
pregnant/breastfeed during treatment and for an additional 6 months
after the last dose of any study treatment or for 12 months after last
dose of cyclophosphamide if administered during optional consolidation
cycle.
233 Female subjects of childbearing pote

Study & Design

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