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

• ClinicalTrials.gov Identifier: NCT04195347
• Recruitment Status: Recruiting
• First Posted: December 11, 2019
• Last Update Posted: March 24, 2023
• Sponsor: St. Jude Children's Research Hospital
• Collaborator: CalciMedica, Inc.
• Information provided by (Responsible Party): St. Jude Children's Research Hospital

Study Description

Brief 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).

Condition or disease	Intervention/treatment	Phase
Acute Pancreatitis	Drug: CM4620	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 42 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: CRSPA: Phase I/II Study of CM4620 to Reduce the Severity of Pancreatitis Due to Asparaginase
• Actual Study Start Date: September 4, 2020
• Estimated Primary Completion Date: June 2025
• Estimated Study Completion Date: December 2025

Arms and Interventions

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 Name: CM4620-IE

Outcome Measures

Primary Outcome Measures :

1. The number of CTCAE grade 3-5 events [ Time Frame: Within 28 days of receiving the medication ]
   Drug safety measuring the number of CTCAE grade 3-5 events
2. Responses to CM4620 [ Time Frame: 28-35 days after study entry. ]
   We will evaluate the rate of pancreatic necrosis or pseudocyst formation using radiographic imaging

Secondary Outcome Measures :

1. Effect of CM4620 measured by levels of pancreatic enzymes [ Time Frame: 72 hours after study entry ]
   Pancreatitis measured by levels of pancreatic enzymes
2. Effect of CM4620: Necrosis [ Time Frame: 28-35 days from study entry ]
   Necrosis measured by levels of pancreatic enzymes
3. Effect of CM4620: Pseudocyst [ Time Frame: 28-35 days from study entry ]
   Pseudocyst measured by levels of pancreatic enzymes
4. Effect of CM4620: Incidence of SIRS [ Time Frame: 48-72 hours after study entry ]
   Presence or absence of systemic inflammatory response syndrome

Eligibility Criteria

• Ages Eligible for Study: up to 21 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Seth E. Karol, MD; 866-278-5833; referralinfo@stjude.org

Locations

United States, Tennessee

St. Jude Children's Research Hospital; Recruiting

Memphis, Tennessee, United States, 38105

Contact: Seth E. Karol, MD 866-278-5833 referralinfo@stjude.org

Principal Investigator: Seth E. Karol, MD

Sponsors and Collaborators

St. Jude Children's Research Hospital

CalciMedica, Inc.

Investigators

• Principal Investigator: Seth E. Karol, MD; St. Jude Children's Research Hospital

More Information

Additional Information:

St. Jude Children's Research Hospital 

ClinicalTrials Open at St. Jude 

• Responsible Party: St. Jude Children's Research Hospital
• ClinicalTrials.gov Identifier: NCT04195347
• Other Study ID Numbers: CRSPA; NCI-2019-08205 ( Registry Identifier: NCI Clinical Trial Registration Program )
• First Posted: December 11, 2019
• Last Update Posted: March 24, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)
• Time Frame: Data will be made available at the time of article publication.
• 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.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by St. Jude Children's Research Hospital:

Acute Pancreatitis; Asparaginase; Asparaginase Associated Pancreatitis; Acute Lymphoblastic Leukemia; Acute Lymphoblastic Lymphoma; CM4620; Children; SIRS; Systemic Inflammatory Response; Young Adults

Additional relevant MeSH terms:

Pancreatitis; Pancreatic Diseases; Digestive System Diseases