Study of CM4620 to Reduce the Severity of Pancreatitis Due to Asparaginase

Acute Pancreatitis Clinical Trial

Official title:

CRSPA: Phase I/II Study of CM4620 to Reduce the Severity of Pancreatitis Due to Asparaginase

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04195347
• Other study ID #: CRSPA
• Secondary ID: NCI-2019-08205
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: September 4, 2020
• Est. completion date: December 2025

Study information

• Verified date: April 2024
• Source: St. Jude Children's Research Hospital
• Contact: Seth E. Karol, MD
• Phone: 866-278-5833
• Email: referralinfo[@]stjude.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a phase I/II clinical trial assessing the tolerability and efficacy of CM4620 in children and young adults with acute pancreatitis caused by asparaginase. The tolerability of CM4620 when given to patients receiving frontline chemotherapy will be determined. The effectiveness in reducing the severity of pancreatitis will be estimated.

Primary Objectives

To assess the safety of CM4620 administration in children and young adults with asparaginase associated pancreatitis (AAP).

To profile dose-limiting toxicities and responses of the patients treated in the dose-finding phase.

To estimate the efficacy of CM4620 to prevent pseudocyst or necrotizing pancreatitis in children with AAP.

Secondary Objectives

To determine the effect of CM4620 on the incidence of severe pancreatitis

To determine the effect of CM4620 on the incidence of Systemic Inflammatory Response Syndrome (SIRS).

Description:

This is an open label safety and efficacy evaluation with comparison of toxicity to a historical control population (TOTXVI). There will be 3 cohorts of patients enrolled, and the dose for each cohort will be determined based on the toxicities experienced in the ongoing and prior cohorts.

An initial 9 patients (cohort 1) will be enrolled and will receive dose level 1 and monitored for toxicity. If the therapy is well tolerated, 6 patients (cohort 2) will be treated at dose level 2. Subsequent enrollment of 9 patients (cohort 3) will be at either dose level 1 or 2 based on tolerability. The keyboard design will be used to determine the dosing for cohorts 2 and 3. Additional patients will be enrolled at the recommended phase II dose (RP2D) until a total of 24 patients have been treated at that dose, including any treated during the dose-finding phase.

CM4620 will be given days 1-4 as an IV infusion beginning within 36 hours of the onset of acute pancreatitis associated abdominal pain and within 8 hours of enrollment. For patients with prior abdominal pain or in those unable to communicate the location/characteristic of their pain, a change in the characteristic of the pain or new enzyme elevation/imaging findings after previously normal studies will determine the timing of onset of pancreatitis.

Patients will be followed for about 4 months after treatment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 42
• Est. completion date: December 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 21 Years

Eligibility

Inclusion Criteria:

• Acute pancreatitis with elevation of amylase OR lipase = 3x 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.

• QTc at baseline > 450 msec.

• Creatinine > 3x the upper limit of normal for age or total bilirubin >3x 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.

Related Conditions & MeSH terms

• Acute Pancreatitis
• Pancreatitis

Intervention

Drug:
• CM4620
IV

Locations

Country	Name	City	State
United States	Novant Health Presbyterian Hemby Children's Hospital	Charlotte	North Carolina
United States	St. Jude Children's Research Hospital	Memphis	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
St. Jude Children's Research Hospital	CalciMedica, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The number of CTCAE grade 3-5 events	Drug safety measuring the number of CTCAE grade 3-5 events	Within 28 days of receiving the medication
Primary	Responses to CM4620	We will evaluate the rate of pancreatic necrosis or pseudocyst formation using radiographic imaging	28-35 days after study entry.
Secondary	Effect of CM4620 measured by levels of pancreatic enzymes	Pancreatitis measured by levels of pancreatic enzymes	72 hours after study entry
Secondary	Effect of CM4620: Necrosis	Necrosis measured by levels of pancreatic enzymes	28-35 days from study entry
Secondary	Effect of CM4620: Pseudocyst	Pseudocyst measured by levels of pancreatic enzymes	28-35 days from study entry
Secondary	Effect of CM4620: Incidence of SIRS	Presence or absence of systemic inflammatory response syndrome	48-72 hours after study entry

External Links

•   ClinicalTrials Open at St. Jude
•   St. Jude Children's Research Hospital