Clinical Trial Summary

The purpose of the study is to determine the maximum tolerated dose and assess the safety,
tolerability and activity of carfilzomib, alone and in combination with induction
chemotherapy, in children with relapsed or refractory acute lymphoblastic leukemia (ALL).

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Phase

Phase 1

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Funding Agency/Sponsor

Amgen

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Disease

Pediatric Cancer

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Enrollment Eligibility

Key Inclusion Criteria:
1. Age 21 years or younger at the time of initial ALL diagnosis and age > 1 year at the
time of study treatment initiation.
2. Subjects must have a diagnosis of relapsed or refractory ALL with ≥ 5% blasts in the
bone marrow (M2 or M3 disease), with or without extramedullary disease.
-To be eligible, subjects must have had 1 or more prior therapeutic attempts, defined
as:
- Early first relapse (< 36 months from original diagnosis) after achieving a CR
(B-ALL) or first relapse any time following the original diagnosis after
achieving a CR (T-ALL)
- Relapse after achieving a CR following the first or subsequent relapse (i.e., ≥ 2
relapses) OR
- Failing to achieve a CR from original diagnosis after at least 1 induction
attempt
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 except in the presence of Gilbert
Syndrome
- Alanine aminotransferase (ALT) ≤ 5 × institutional ULN
6. Performance status: Karnofsky or Lansky scores ≥ 50 for subjects > 16 years old or ≤
16 years old, respectively.
Key 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)
3. Left ventricular fractional shortening < 30%
4. History of ≥ Grade 2 pancreatitis
5. Active graft‑versus‑host disease requiring systemic treatment
6. Positive culture for or other clinical evidence of infection with bacteria or fungus
within 14 days of the initiation of study treatment
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 study treatment
initiation, or at least 14 days before study treatment initiation, if pegylated
myeloid growth factors were administered.
- Subjects must have completed any type of active immunotherapy (e.g., tumor
vaccines) at least 42 days before study treatment initiation.
- At least 3 antibody half‑lives must have elapsed since the last dose of
monoclonal antibody (e.g., 66 days for rituximab and 69 days for epratuzumab)
before subjects may initiate study treatment.
- Subjects must have completed any type of active immunotherapy (e.g., tumor
vaccines) at least 42 days before study treatment initiation.
- Subjects must not have received other antineoplastic agents with therapeutic
intent, excluding hydroxyurea and antimetabolites administered as part of
maintenance chemotherapy, within 7 days prior to study treatment initiation

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