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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Acute Pancreatitis
• Intervention / Treatment: Drug: CM4620

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Seth E. Karol, MD; Phone Number: 866-278-5833; Email: referralinfo@stjude.org

Study Locations

• United States
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Recruiting
      • Novant Health Presbyterian Hemby Children's Hospital
      • Contact: Jessica Bell, MD
      • Contact: Phone Number: 704-384-1900; Email: jbell@novanthealth.org
      • Principal Investigator: Jessica Bell, MD
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • Recruiting
      • St. Jude Children's Research Hospital
      • Contact: Seth E. Karol, MD; Phone Number: 866-278-5833; Email: referralinfo@stjude.org
      • Principal Investigator: Seth E. Karol, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CM4620 Treatment; Phase I: Cohort 1 patients receive CM4620 IV at dose level 1 on days 1-4. Cohort 2 patients receive CM4620 IV at dose level 2 on days 1-4. Cohort 3 patients receive CM4620 IV at either dose level 1 or 2 on days 1-4 Phase II: Patients will receive CM4620 IV on days 1-4 at the recommended Phase II dose (RP2D) as determined in Phase I.	Drug: CM4620; IV; Other Names: CM4620-IE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Responses to CM4620	We will evaluate the rate of pancreatic necrosis or pseudocyst formation using radiographic imaging	28-35 days after study entry.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of CM4620 measured by levels of pancreatic enzymes	Pancreatitis measured by levels of pancreatic enzymes	72 hours after study entry
Effect of CM4620: Necrosis	Necrosis measured by levels of pancreatic enzymes	28-35 days from study entry
Effect of CM4620: Pseudocyst	Pseudocyst measured by levels of pancreatic enzymes	28-35 days from study entry
Effect of CM4620: Incidence of SIRS	Presence or absence of systemic inflammatory response syndrome	48-72 hours after study entry

Collaborators and Investigators

• Sponsor: St. Jude Children's Research Hospital
• Collaborators: CalciMedica, Inc.
• Investigators: Principal Investigator: Seth E. Karol, MD, St. Jude Children's Research Hospital

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): September 4, 2020
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: November 25, 2019
• First Submitted That Met QC Criteria: December 9, 2019
• First Posted (Actual): December 11, 2019

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Children; Acute Lymphoblastic Leukemia; Acute Pancreatitis; Asparaginase; Asparaginase Associated Pancreatitis; Acute Lymphoblastic Lymphoma; CM4620; SIRS; Systemic Inflammatory Response; Young Adults
• Additional Relevant MeSH Terms: Digestive System Diseases; Pancreatic Diseases; Pancreatitis
• Other Study ID Numbers: CRSPA; NCI-2019-08205 (Registry Identifier: NCI Clinical Trial Registration Program)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant de-identified datasets containing the variables analyzed in the published article will be made available (related to the study primary or secondary objectives contained in the publication). Supporting documents such as the protocol, statistical analyses plan, and informed consent are available through the CTG website for the specific study. Data used to generate the published article will be made available at the time of article publication. Investigators who seek access to individual level de-identified data will contact the computing team in the Department of Biostatistics (ClinTrialDataRequest@stjude.org) who will respond to the data request.
• IPD Sharing Time Frame: Data will be made available at the time of article publication.
• IPD Sharing Access Criteria: Data will be provided to researchers following a formal request with the following information: full name of requestor, affiliation, data set requested, and timing of when data is needed. As an informational point, the lead statistician and study principal investigator will be informed that primary results datasets have been requested.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No