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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CM4620 (also known as Auxora) for children and young adults with acute pancreatitis caused by the chemotherapy drug asparaginase. The main goal is to determine if CM4620 is safe and can prevent serious complications like pseudocysts or necrotizing pancreatitis in patients. The trial will also assess whether CM4620 can reduce the severity of pancreatitis and related issues. Those who have recently received asparaginase treatment for acute lymphoblastic leukemia or lymphoma and are experiencing pancreatitis symptoms might be suitable candidates. As a Phase 1, Phase 2 trial, this research aims to understand how CM4620 works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking treatment development.

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.

Is there any evidence suggesting that CM4620 is likely to be safe for humans?

Research has shown that CM4620 has been safe in earlier studies. One study found it might be a good early treatment for people with sudden inflammation of the pancreas and a severe reaction to infection. Another study found that CM4620 helped reduce the severity of pancreatitis, including serious breathing problems and a severe form of the condition. These findings suggest that CM4620 is generally well-tolerated, with no major safety issues reported so far. However, this trial remains in its early stages, so more information is needed to fully confirm its safety for treating pancreatitis in this specific situation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pancreatitis?

Unlike the standard treatments for pancreatitis, which often focus on managing symptoms with pain relief and fluid replacement, CM4620 targets the root cause by inhibiting calcium overload in pancreatic cells. This novel mechanism helps prevent cell damage and inflammation, potentially speeding up recovery and reducing complications. Researchers are excited about CM4620 because it offers a more direct approach to treating pancreatitis, potentially leading to faster relief and better outcomes for patients.

What evidence suggests that CM4620 might be an effective treatment for pancreatitis?

Research has shown that CM4620, also known as Auxora, may reduce the severity of sudden pancreatitis. Studies have found that it significantly lowers the risk of serious complications like necrotizing pancreatitis, a severe form of the condition. In earlier studies, patients who received CM4620 experienced better outcomes, including fewer cases of breathing failure. The treatment has also proven safe, making it a promising early option for people with pancreatitis and related issues like Systemic Inflammatory Response Syndrome (SIRS). These findings suggest that CM4620 could be very helpful for those with pancreatitis caused by asparaginase. ^{1 2 3 4 5}

Who Is on the Research Team?

Seth E. Karol, MD

Principal Investigator

St. Jude Children's Research Hospital

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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).

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. ir.calcimedica.com ir.calcimedica.com/news-releases/news-release-details/calcimedica-announces-positive-topline-data-phase-2b-carpo-trial

CalciMedica Announces Positive Topline Data from Phase ... Primary objective of the trial met with statistically significant dose response with up to 43.6% relative reduction (2.1 day improvement) in ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04195347

Study of CM4620 to Reduce the Severity of Pancreatitis ... 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 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8104014/

Auxora for the Treatment of Patients With Acute Pancreatitis ... The favorable safety profile and patient outcomes suggest Auxora may be an appropriate early treatment for patients with AP and SIRS.

4. academic.oup.com academic.oup.com/function/article/5/4/zqae017/7641404

Combination of the CRAC Channel Inhibitor CM4620 and ... The ability of micromolar concentrations of CM4620 to significantly reduce mouse PAC necrosis elicited by AP-inducing agents was demonstrated previously.33,42 ...

5. ir.calcimedica.com ir.calcimedica.com/news-releases/news-release-details/calcimedica-present-late-breaking-positive-data-including-win

CalciMedica to Present Late-Breaking Positive Data ... Auxora continues to deliver across key AP endpoints, showing that the drug substantially reduced respiratory failure, necrotizing pancreatitis, and long ...