What side effects are associated with this type of intervention?

Common treatments for Acute Myeloid Leukemia (AML) like CPX-351 (a combination of cytarabine and daunorubicin) and Glasdegib have notable side effects. CPX-351 can cause myelosuppression, gastrointestinal symptoms, mucositis, alopecia, and increased infection risk. Glasdegib, a Hedgehog pathway inhibitor, may lead to fatigue, nausea, decreased appetite, dysgeusia, and muscle spasms. These side effects necessitate careful management to maintain patient quality of life.

What prior FDA approvals exist?

The FDA has approved several treatments for Acute Myeloid Leukemia (AML) that interfere with DNA synthesis and function, including CPX-351, a liposomal formulation of cytarabine and daunorubicin. This combination is designed to deliver a synergistic ratio of the two drugs directly to the leukemia cells. Additionally, the Hedgehog pathway inhibitor Glasdegib has been approved for use in combination with low-dose cytarabine for newly diagnosed AML in patients who are not candidates for intensive chemotherapy. These approvals highlight the ongoing efforts to target specific pathways and mechanisms involved in AML to improve treatment outcomes.

What other types of research exist?

Promising novel alternatives for AML treatment include HMA (hypomethylating agents) combined with venetoclax or ivosidenib. These combinations have shown improved outcomes compared to HMA monotherapy. Additionally, azacitidine plus gilteritinib has demonstrated a higher overall response rate compared to azacitidine plus placebo.

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Chemotherapy

CPX-351 + Glasdegib for Acute Myeloid Leukemia

Phase 2

Waitlist Available

Led By Deepa Jeyakumar, MD

Research Sponsored by University of California, Irvine

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from the start date of treatment until 4 weeks after removal of treatment due to disease progression, toxicity, delay of treatment, or withdrawal of treatment, whichever came first, an average of 1 year.

Awards & highlights

All Individual Drugs Already Approved

Approved for 5 Other Conditions

No Placebo-Only Group

Summary

This trial is testing a combination of two drugs, CPX-351 and Glasdegib, in patients with a specific type of leukemia that is hard to treat. CPX-351 kills cancer cells, and Glasdegib stops them from growing. The goal is to see if this combination is effective for these patients.

Who is the study for?

Adults over 18 with newly diagnosed, untreated Acute Myelogenous Leukemia (AML) that's related to prior therapy or myelodysplastic syndromes. Participants must have good heart function and organ health, not be pregnant or breastfeeding, agree to use birth control, and cannot have certain heart conditions, uncontrolled infections, other active cancers requiring treatment, or a history of severe medical disorders.

What is being tested?

The trial is testing the effectiveness of combining two drugs: CPX-351 (a chemotherapy drug) and Glasdegib (a targeted therapy), in treating AML. It's an open-label study where all participants receive the same treatment without a comparison group.

What are the potential side effects?

Possible side effects include nausea, vomiting, diarrhea; low blood cell counts leading to increased infection risk; fatigue; liver problems; muscle pain; shortness of breath; and potential for heart rhythm abnormalities.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from the start date of treatment until 4 weeks after removal of treatment due to disease progression, toxicity, delay of treatment, or withdrawal of treatment, whichever came first, an average of 1 year.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from the start date of treatment until 4 weeks after removal of treatment due to disease progression, toxicity, delay of treatment, or withdrawal of treatment, whichever came first, an average of 1 year.

This trial's timeline: 3 weeks for screening, Varies for treatment, and from the start date of treatment until 4 weeks after removal of treatment due to disease progression, toxicity, delay of treatment, or withdrawal of treatment, whichever came first, an average of 1 year. for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Percentage of Participants with Event-Free Survival at 6 months

Secondary study objectives

Durability of Response

Hemopoietic stem cell transplant

Overall Response Rate

+3 more

Side effects data

From 2015 Phase 3 trial • 309 Patients • NCT01696084

68%

Febrile Neutropenia

49%

Nausea

46%

Diarrhoea

42%

Constipation

41%

Oedema Peripheral

35%

Headache

35%

Epistaxis

35%

Fatigue

33%

Cough

33%

Decreased Appetite

29%

Rash

27%

Chills

25%

Vomiting

24%

Dyspnoea

24%

Insomnia

22%

Abdominal Pain

22%

Pyrexia

21%

Dizziness

20%

Hypotension

20%

Hypoxia

19%

Hypertension

18%

Pneumonia

18%

Mucosal Inflammation

18%

Oropharyngeal Pain

17%

Pleural Effusion

16%

Arthralgia

15%

Pruritus

15%

Anxiety

14%

Tachycardia

14%

Petechiae

14%

Back Pain

13%

Confusional State

13%

Pain In Extremity

12%

Abdominal Distension

12%

Haemorrhoids

10%

Mouth Haemorrhage

Rash Maculo-Papular

Erythema

Stomatitis

Dyspepsia

Asthenia

Night Sweats

Blood Blister

Dysgeusia

Fluid Overload

Bacteraemia

Transfusion Reaction

Haemoptysis

Sepsis

Gingival Bleeding

Oedema

Procedural Pain

Fall

Neck Pain

Pulmonary Oedema

Rales

Respiratory Failure

Hyperhidrosis

Wheezing

Vision Blurred

Dry Mouth

Chest Pain

Catheter Site Pain

Musculoskeletal Pain

Depression

Renal Failure Acute

Haematuria

Rash Pruritic

Ecchymosis

Urinary Incontinence

Abdominal Pain Upper

Nasal Congestion

Mouth Ulceration

Ejection Fraction Decreased

Dysphagia

Catheter Site Erythema

Cellulitis

Contusion

Myalgia

Pollakiuria

Deep Vein Thrombosis

Dry Skin

Hiccups

Tachypnoea

Dysuria

Atrial Fibrillation

Conjunctival Haemorrhage

Chest Discomfort

Agitation

Acute Respiratory Failure

Disease Progression

Delirium

Rash Erythematous

Syncope

Muscular Weakness

Gastrooesophageal Reflux Disease

Skin Lesion

Oral Pain

Hallucination

Alopecia

Weight Decreased

Central Nervous System Haemorrhage

Myocardial Infarction

Somnolence

Stenotrophomonas Test Positive

Streptococcus Test Positive

Cerebral Haemorrhage

Mental Status Changes

Haemorrhage Intracranial

Fungal Test Positive

Pancytopenia

Euthyroid Sick Syndrome

Hypothyroidism

Urinary Tract Infection

Enterococcus Test Positive

Hepatic Enzyme Increased

Neutropenia

Pneumonia Bacterial

Bacteroides Bacteraemia

Streptococcal Sepsis

Pseudomonas Test Positive

Staphylococcus Test Positive

Staphylococcal Bacteraemia

Bronchopulmonary Aspergillosis

Sinusitis Fungal

Skin Infection

Pneumonia Aspiration

Pneumothorax

Transfusion-Related Acute Lung Injury

Alloimmunisation

Anaemia

Thrombocytopenia

Cardiac Failure

Cardiac Arrest

Cardiac Failure Congestive

Cardiomyopathy

Mitral Valve Incompetence

Pericarditis

Small Intestinal Disorders

Chron's Disease

Gastric Haemorrhage

Lower Gastrointestinal Haemorrhage

Multi-Organ Failure

Death

Non-Cardiac Chest Pain

Cholecystitis Acute

Bile Duct Stone

Septic Shock

Enterococcal Bacteraemia

Diverticulitis

Enterobacter Bacteraemia

Mycotic Aneurysm

Neutropenic Infection

Pseudomonal Bacteraemia

Sinusitis

Dehydration

Lactic Acidosis

Acute Myeloid Leukaemia

Acute Myeloid Leukaemia Recurrent

Myelodysplastic Syndrome

Renal Cell Carcinoma

Carotid Artery Stenosis

Cerebral Infarction

Convulsion

Presyncope

Radiculopathy

Acute Respiratory Distress Syndrome

100%

80%

60%

40%

20%

Study treatment Arm

Arm A (CPX-351)

Arm B (7+3)

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Approved for 5 Other Conditions

This treatment demonstrated efficacy for 5 other conditions.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: CPX-351 and GlasdegibExperimental Treatment2 Interventions

In Induction, subjects receive 44mg/m2/100mg/m2 IV on days 1, 3 and 5 and Glasdegib 100mg PO daily on days 6 to 28. If re-induction is needed: Subjects receive 44mg/m2/100mg/m2 IV on days 1 and 3 and Glasdegib 100mg PO daily on days 4 to 28. In consolidation: Subjects receive 29mg/m2/65mg/m2 IV on days 1 and 3 and Glasdegib 100mg PO daily on days 4 to 28. If maintenance is required, Subjects receive Glasdegib 100mg PO daily for up to one year

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Daunorubicin

FDA approved

Glasdegib

FDA approved

Do I qualify?Apply below to find out

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

CPX-351, a combination of cytarabine and daunorubicin, interferes with DNA synthesis and function, leading to the death of rapidly dividing leukemia cells. Glasdegib, a Hedgehog pathway inhibitor, disrupts a critical signaling pathway for leukemia stem cell survival and proliferation. These mechanisms are crucial for AML patients as they target both the bulk leukemia cells and the leukemia stem cells, potentially leading to more effective and durable treatment outcomes.

Molecular targeting in acute myeloid leukemia.Targeting the PI3K/AKT pathway via GLI1 inhibition enhanced the drug sensitivity of acute myeloid leukemia cells.Targeting phosphatidylinositol 3-kinase signaling in acute myelogenous leukemia.