CM4620 for Pancreatitis

Recruiting at 1 trial location

Overseen By Seth E. Karol, MD

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: St. Jude Children's Research Hospital

Must be taking: Asparaginase

Must not be taking: Investigational agents

Disqualifiers: Prior pancreatitis, High QTc, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4 days

42 Participants Needed

Trial Summary

What is the purpose of this trial?

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).

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are taking another investigational agent, you must stop it at least 7 days before joining the trial.

What makes the drug CM4620 (Auxora) unique for treating pancreatitis?

CM4620 (Auxora) is unique because it targets specific pathways involved in inflammation, potentially offering a novel approach to managing pancreatitis compared to traditional treatments that focus on symptom relief and supportive care. ^{1 2 3 4 5}

Research Team

Seth E. Karol, MD

Principal Investigator

St. Jude Children's Research Hospital

Eligibility Criteria

This trial is for children and young adults under 22 with acute lymphoblastic leukemia/lymphoma who are undergoing treatment. They must have recent pancreatitis linked to asparaginase therapy, no history of egg allergy or sensitivity to CM4620 components, normal kidney and liver function tests, no other investigational drugs taken in the last week, no prior pancreatitis episodes, a safe QTc interval on ECG, not be pregnant or breastfeeding, and agree to use contraception.

Inclusion Criteria

I have not received asparaginase treatment in the last 35 days.

I am under 22 and being treated for acute lymphoblastic leukemia/lymphoma with the goal of curing it.

I have acute pancreatitis with high enzyme levels and either pain or imaging that confirms it.

Exclusion Criteria

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.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

Treatment

Participants receive CM4620 IV infusion on days 1-4 at varying dose levels based on cohort assignment

4 days

Daily visits for IV infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 months

Regular follow-up visits

Dose-finding

Dose levels are adjusted based on toxicity and tolerability in cohorts

Varies by cohort

Treatment Details

Interventions

• CM4620

Trial Overview The study is testing CM4620's safety and ability to reduce the severity of pancreatitis caused by asparaginase in young patients. It will look at what doses are safe (phase I) and how well it works to prevent serious complications like pseudocysts or necrotizing pancreatitis (phase II).

Participant Groups

Group I: CM4620 Treatment Experimental Treatment 1 Intervention

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.

CM4620 is already approved in United States for the following indications:

Approved in United States as Auxora for:

• Acute pancreatitis with accompanying Systemic Inflammatory Response Syndrome (SIRS)

Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

CalciMedica, Inc.

Industry Sponsor

Trials

8

Recruited

730+

Findings from Research

The M-ANNHEIM-Surgery-Score effectively predicts the need for pancreatic surgery in chronic pancreatitis patients, with a sensitivity of 78.7% and specificity of 91%, based on a study of 741 patients across multiple locations.

Patients categorized in the 'High-Demand' group for surgery had a significantly higher likelihood of requiring surgery (54%) compared to those in the 'Baseline-Demand' (1.6%) and 'Low-Demand' (7%) categories, highlighting the score's utility in clinical decision-making.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical evaluation of the M-ANNHEIM classification: Development of the M-ANNHEIM-Surgery-Score as a new tool to monitor patients with chronic pancreatitis. Hirth, M., Weiss, C., Rückert, F., et al.[2022]

Recent research has identified a new genetic mutation (TRPV6) linked to pancreatitis, particularly in Northern European populations, which could improve genetic screening and understanding of the disease.

Innovations in the management of acute pancreatitis, such as early introduction of low-fat solid foods and a shift towards non-operative treatments for infected pancreatic necrosis, have been shown to reduce complications and hospital stays, enhancing patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in acute and chronic pancreatitis. Strum, WB., Boland, CR.[2023]

The traditional classification of pancreatitis from 1963, which includes acute and chronic forms, is often challenging to apply in clinical practice, particularly in diagnosing chronic pancreatitis.

A study of 54 patients revealed that the current diagnostic criteria for chronic pancreatitis may be difficult to interpret, suggesting a need for a revised classification system that reflects advancements in diagnostic techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the diagnosis pancreatitis. Seligson, U., Cho, JW., Ihre, T., et al.[2019]

Chronic pancreatitis (CP) is a serious condition that leads to irreversible damage to the pancreas, and early diagnosis using MRI/MRCP is crucial for effective management, especially in assessing pain, which significantly affects quality of life.

Endoscopic therapy (ET) is recommended as an early treatment option for managing pain in CP, and it can be combined with techniques like extracorporeal shock-wave lithotripsy for obstructive stones, highlighting the importance of tailored interventions based on individual patient needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belgian consensus on chronic pancreatitis in adults and children: statements on diagnosis and nutritional, medical, and surgical treatment. Delhaye, M., Van Steenbergen, W., Cesmeli, E., et al.[2016]

In a study of 20 dogs with subclinical exocrine pancreatic insufficiency (EPI), treatment with the immunosuppressive drug azathioprine did not significantly prevent the progression to clinical EPI, as some treated dogs developed symptoms after stopping the medication.

The progression of atrophic lymphocytic pancreatitis was variable, with some dogs remaining asymptomatic for years, suggesting that early treatment with immunosuppressive drugs may not be necessary or beneficial due to the slow natural progression of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subclinical exocrine pancreatic insufficiency in dogs. Wiberg, ME., Westermarck, E.[2019]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Clinical evaluation of the M-ANNHEIM classification: Development of the M-ANNHEIM-Surgery-Score as a new tool to monitor patients with chronic pancreatitis. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Advances in acute and chronic pancreatitis. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Evaluation of the diagnosis pancreatitis. [2019]

4. Belgium pubmed.ncbi.nlm.nih.gov

Belgian consensus on chronic pancreatitis in adults and children: statements on diagnosis and nutritional, medical, and surgical treatment. [2016]

5. United States pubmed.ncbi.nlm.nih.gov

Subclinical exocrine pancreatic insufficiency in dogs. [2019]