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

Primary Purpose

Acute Pancreatitis

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

CM4620

About this trial

This is an interventional treatment trial for Acute Pancreatitis focused on measuring Acute Pancreatitis, Asparaginase, Asparaginase Associated Pancreatitis, Acute Lymphoblastic Leukemia, Acute Lymphoblastic Lymphoma, CM4620, Children, SIRS, Systemic Inflammatory Response, Young Adults

Eligibility Criteria

undefined - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Novant Health Presbyterian Hemby Children's HospitalRecruiting
St. Jude Children's Research HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CM4620 Treatment

Arm Description

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.

Outcomes

Primary Outcome Measures

The number of CTCAE grade 3-5 events

Drug safety measuring the number of CTCAE grade 3-5 events

Responses to CM4620

We will evaluate the rate of pancreatic necrosis or pseudocyst formation using radiographic imaging

Secondary Outcome Measures

Effect of CM4620 measured by levels of pancreatic enzymes

Pancreatitis measured by levels of pancreatic enzymes

Effect of CM4620: Necrosis

Necrosis measured by levels of pancreatic enzymes

Effect of CM4620: Pseudocyst

Pseudocyst measured by levels of pancreatic enzymes

Effect of CM4620: Incidence of SIRS

Presence or absence of systemic inflammatory response syndrome

Full Information

NCT ID

NCT04195347

First Posted

November 25, 2019

Last Updated

October 10, 2023

Sponsor

St. Jude Children's Research Hospital

Collaborators

CalciMedica, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT04195347

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Recruiting

Study Start Date

September 4, 2020 (Actual)

Primary Completion Date

June 2025 (Anticipated)

Study Completion Date

December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

St. Jude Children's Research Hospital

Collaborators

CalciMedica, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. 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).

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Pancreatitis

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

42 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

CM4620 Treatment

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

CM4620

Other Intervention Name(s)

CM4620-IE

Intervention Description

Primary Outcome Measure Information:

Title

The number of CTCAE grade 3-5 events

Description

Drug safety measuring the number of CTCAE grade 3-5 events

Time Frame

Within 28 days of receiving the medication

Title

Responses to CM4620

Description

We will evaluate the rate of pancreatic necrosis or pseudocyst formation using radiographic imaging

Time Frame

28-35 days after study entry.

Secondary Outcome Measure Information:

Title

Effect of CM4620 measured by levels of pancreatic enzymes

Description

Pancreatitis measured by levels of pancreatic enzymes

Time Frame

72 hours after study entry

Title

Effect of CM4620: Necrosis

Description

Necrosis measured by levels of pancreatic enzymes

Time Frame

28-35 days from study entry

Title

Effect of CM4620: Pseudocyst

Description

Pseudocyst measured by levels of pancreatic enzymes

Time Frame

28-35 days from study entry

Title

Effect of CM4620: Incidence of SIRS

Description

Presence or absence of systemic inflammatory response syndrome

Time Frame

48-72 hours after study entry

10. Eligibility

Sex

All

Maximum Age & Unit of Time

21 Years

Accepts Healthy Volunteers

Eligibility 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Seth E. Karol, MD

Phone

866-278-5833

referralinfo@stjude.org

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Seth E. Karol, MD

Organizational Affiliation

St. Jude Children's Research Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Novant Health Presbyterian Hemby Children's Hospital

City

Charlotte

State/Province

North Carolina

ZIP/Postal Code

28204

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jessica Bell, MD

Phone

704-384-1900

jbell@novanthealth.org

First Name & Middle Initial & Last Name & Degree

Jessica Bell, MD

Facility Name

St. Jude Children's Research Hospital

City

Memphis

State/Province

Tennessee

ZIP/Postal Code

38105

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Seth E. Karol, MD

Phone

866-278-5833

referralinfo@stjude.org

First Name & Middle Initial & Last Name & Degree

Seth E. Karol, MD

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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.

Links:

URL

http://www.stjude.org

Description

St. Jude Children's Research Hospital

URL

http://www.stjude.org/protocols

Description

ClinicalTrials Open at St. Jude

Learn more about this trial

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

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