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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Acute Pancreatitis

Intervention / Treatment
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* Drug: CM4620


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CM4620 Treatment<br>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<br>* IV<br>* Other names: CM4620-IE;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Pancreatitis, Asparaginase, Asparaginase Associated Pancreatitis, Acute Lymphoblastic Leukemia, Acute Lymphoblastic Lymphoma, CM4620, Children, SIRS, Systemic Inflammatory Response, Young Adults