Clinical trial NCT04195347: 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
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Acute Pancreatitis
Keywords: Acute Pancreatitis
Asparaginase
Asparaginase Associated Pancreatitis
Acute Lymphoblastic Leukemia
Acute Lymphoblastic Lymphoma
CM4620
Children
SIRS
Systemic Inflammatory Response
Young Adults
Lead sponsor: St. Jude Children's Research Hospital
Sponsor class: OTHER
Collaborators: name: CalciMedica, Inc.
First posted: 2019-12-11
Enrollment: 42
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: The number of CTCAE grade 3-5 events
timeFrame: Within 28 days of receiving the medication
measure: Responses to CM4620
timeFrame: 28-35 days after study entry.
Secondary outcomes:
measure: Effect of CM4620 measured by levels of pancreatic enzymes
timeFrame: 72 hours after study entry
measure: Effect of CM4620: Necrosis
timeFrame: 28-35 days from study entry
measure: Effect of CM4620: Pseudocyst
timeFrame: 28-35 days from study entry
measure: Effect of CM4620: Incidence of SIRS
timeFrame: 48-72 hours after study entry
Other outcomes:
Locations:
city: Charlotte
country: United States
facility: Novant Health Presbyterian Hemby Children's Hospital
state: North Carolina
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
Study officials:
affiliation: St. Jude Children's Research Hospital
name: Seth E. Karol, MD
role: PRINCIPAL_INVESTIGATOR
References: