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CM4620 for the Reduction of the Severity of Acute Pancreatitis Due to Treatment with Asparaginase in Patients with Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma, the CRSPA Study
Trial Status: active
This phase I/II trial studies the side effects and best dose of CM4620 and to see how well it works in reducing the severity of acute pancreatitis due to the drug asparaginase in patients with acute lymphoblastic leukemia or lymphoblastic lymphoma. Pancreatitis is severe inflammation of the pancreas, causing pain in the upper abdomen. It can become severe and cause nausea and vomiting, fever and rapid heart rate. Pancreatitis may require hospitalization and may be life threatening. CM4620 may help reduce the severity of acute pancreatitis in patients with acute lymphoblastic leukemia or lymphoblastic lymphoma.
Inclusion Criteria
Acute pancreatitis with elevation of amylase OR lipase >= 3 x the upper limit of normal AND at least 1 of: abdominal pain consistent with acute pancreatitis OR imaging findings consistent with acute pancreatitis
Receipt of any form of asparaginase within the prior 35 days
Patient with acute lymphoblastic leukemia/ lymphoma age < 22 years receiving therapy with curative intent
Exclusion Criteria
Prior episode of pancreatitis
Corrected QT (QTc) at baseline > 450 msec
Creatinine > 3 x the upper limit of normal for age or total bilirubin > 3 x the upper limit for normal for age without evidence of leukemic infiltrate or hemolysis
Receipt of another investigational agent within the prior 7 days
History of allergy to eggs or known hypersensitivity to any component of CM4620
Positive pregnancy test or breastfeeding. Females of childbearing potential must have a negative urine or serum pregnancy test prior to enrollment. Males and females of childbearing potential must agree to use effective contraception for at least twelve months following the completion of therapy
Inability or unwillingness of research participant or legal guardian/representative to give written informed consent
Additional locations may be listed on ClinicalTrials.gov for NCT04195347.
I. To assess the safety of calcium release-activated channel inhibitor CM4620 (CM4620) administration in children and young adults with asparaginase associated pancreatitis (AAP).
II. To profile dose-limiting toxicities and responses of the patients treated in the dose-finding phase.
III. To estimate the efficacy of CM4620 to prevent pseudocyst or necrotizing pancreatitis in children with AAP.
SECONDARY OBJECTIVES:
I. To determine the effect of CM4620 on the incidence of severe pancreatitis.
II. To determine the effect of CM4620 on the incidence of systemic inflammatory response syndrome (SIRS).
EXPLORATORY OBJECTIVES:
I. Determine the pharmacokinetics of CM4620 in children with AAP.
II. To evaluate the prognostic significance of computerized tomography (CT) or magnetic resonance imaging (MRI) findings within 24 hours of the diagnosis of pancreatitis in children with AAP.
III. To identify novel biomarkers of AAP severity.
IV. Evaluate severity of pancreatitis as measured by duration of vasopressor support, duration of total parenteral nutrition (TPN), length of hospital stay, need for surgical or interventional radiology intervention, and recurrent pancreatitis with re-exposure to asparaginase.
OUTLINE: This is a dose-escalation study. NOTE: Following the activation of amendment 4, it was determined no dose escalation was indicated, declared dose level 1 as the RP2D, and opened dose level 1 for the phase 2 expansion.
Beginning within 36 hours of the onset of acute pancreatitis and within 8 hours of enrollment, patients receive CM4620 intravenously (IV) over 4 hours for 4 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at days 8, 15, 22 (+/- 2 days), and 29 (+/- 3 days), and 4 months after study entry.
Trial PhasePhase I/II
Trial Typetreatment
Lead OrganizationSaint Jude Children's Research Hospital
