What side effects are associated with this type of intervention?

The most common treatments for Chronic Myelomonocytic Leukemia (CMML) include Cladribine, Cytarabine, Venetoclax, and Azacitidine. Cladribine often causes myelosuppression, leading to infections and anemia. Cytarabine can result in myelosuppression and gastrointestinal symptoms such as nausea and vomiting. Venetoclax frequently causes neutropenia, increasing the risk of infections, and gastrointestinal issues. Azacitidine is associated with cytopenias, febrile neutropenia, and gastrointestinal symptoms. These side effects necessitate careful monitoring and management to maintain patient quality of life.

What prior FDA approvals exist?

For the treatment of Chronic Myelomonocytic Leukemia (CMML), FDA-approved drugs include hypomethylating agents like Azacitidine and Decitabine, which have shown efficacy in managing the disease. Venetoclax, a BCL-2 inhibitor, is approved for use in combination with hypomethylating agents for certain hematologic malignancies and is being explored for CMML. Cytarabine, a cytosine nucleoside analog, is commonly used in various leukemias, including CMML. Cladribine, a purine nucleoside analog, is primarily used for other hematologic conditions but is being studied for its potential in CMML. These drugs represent the main categories of treatments being investigated for their combined efficacy in CMML.

What other types of research exist?

Promising novel alternatives for CMML patients include: 1) Decitabine with sapacitabine, which has shown similar outcomes to decitabine alone in a phase 3 trial. 2) Azacitidine plus gilteritinib, which has demonstrated a higher overall response rate compared to azacitidine plus placebo. These alternatives offer different mechanisms of action and may provide additional options for patients considering treatment in 2024.

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Anti-metabolites

Combination Chemotherapy for Chronic Myelomonocytic Leukemia & Myelodysplastic Syndrome

Q: What is the mechanism of action of this treatment?

Cladribine, a purine nucleoside analog, interferes with DNA synthesis, leading to cell death, particularly in rapidly dividing cells like leukemic cells. Cytarabine, a cytosine nucleoside analog, also inhibits DNA synthesis by incorporating into DNA and preventing replication. Venetoclax, a BCL-2 inhibitor, promotes apoptosis by inhibiting the BCL-2 protein, which normally helps cancer cells survive. Azacitidine, a hypomethylating agent, incorporates into DNA and RNA, leading to hypomethylation and reactivation of tumor suppressor genes, thereby inhibiting cancer cell growth. These mechanisms are crucial for CMML patients as they target the abnormal proliferation and survival of leukemic cells, aiming to control the disease and improve patient outcomes.

Phase 2

Recruiting

Led By Guillermo Bravo, MD

Research Sponsored by M.D. Anderson Cancer Center

Eligibility Criteria Checklist

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

Must have

Diagnosis of MDS or CMML by WHO

Eastern Cooperative Oncology Group (ECOG) performance status of </= 2

Must not have

Female patients without negative pregnancy test

History of HIV disease

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

All Individual Drugs Already Approved

Approved for 5 Other Conditions

No Placebo-Only Group

Summary

This trial uses a combination of four drugs to treat certain blood cancers in patients who have not responded to other treatments or are at high risk. The drugs work together to kill cancer cells and stop their growth.

Who is the study for?

Adults with higher-risk chronic myelomonocytic leukemia (CMML) or myelodysplastic syndromes (MDS) who have not responded to previous treatments. Participants must be over 18, have a white blood cell count under 50,000/L, and an ECOG performance status of <=2. They should also have adequate kidney and liver function and agree to use contraception if they can reproduce.

What is being tested?

The trial is testing whether a combination of drugs—cladribine, cytarabine, venetoclax, and azacitidine—is effective in controlling higher-risk MDS with excess blasts or CMML. It aims to find out if this drug regimen can help patients who haven't had success with other therapies.

What are the potential side effects?

Potential side effects may include nausea, vomiting, diarrhea, low blood counts leading to increased infection risk or bleeding problems; fatigue; liver issues; kidney dysfunction; and potential allergic reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have been diagnosed with MDS or CMML.

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I can take care of myself and perform daily activities.

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My liver is functioning well.

Select...

My MDS is high risk and didn't improve after 6 treatment cycles.

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My MDS is high risk with more than 10% blasts or newly diagnosed.

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I am 18 years old or older.

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My CMML did not improve after 6 treatments or it got worse.

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I have CMML and haven't received HMA treatment.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I am not pregnant or have confirmed it with a test.

Select...

I have a history of HIV.

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My heart's pumping ability is significantly reduced.

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I have an infection that isn't getting better with antibiotics.

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I have had a recent heart attack or unstable chest pain.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Side effects data

From 2011 Phase 3 trial • 867 Patients • NCT00641537

24%

Back pain

20%

Neutropenia

12%

Lymphopenia

12%

Influenza like illness

12%

Fatigue

12%

Influenza

12%

Hyperthermia

Depression

Carpal tunnel syndrome

Viral upper respiratory tract infection

Uterine leiomyoma

Upper respiratory tract infection

Pain in extremity

Headache

Arthralgia

Anxiety

Hypertension

Anaemia of pregnancy

Eye irritation

Eye pruritus

Gastrooesophageal reflux disease

Hypersensitivity

Respiratory tract infection viral

Viral infection

Herpes zoster

Sinusitis

Infected insect bite

Skin bacterial infection

Contusion

Joint sprain

Liver function test abnormal

Weight decreased

Dizziness

Joint swelling

Pharyngolaryngeal pain

Cough

Restless legs syndrome

Pregnancy

Depressed mood

Abortion threatened

Iron deficiency anaemia

Erythema infectiosum

Tooth disorder

Faecal incontinence

Injection site abscess

White blood cell count decreased

Sensation of heaviness

Syncope

100%

80%

60%

40%

20%

Study treatment Arm

Cladribine 3.5 mg/kg/No Treatment

Cladribine 5.25 mg/kg/No Treatment

Cladribine Low/Placebo (LLPP)

Cladribine High Dose/Placebo (HLPP)

Cladribine Low/Low Dose (LLLL)

Cladribine High/Low Dose (HLLL)

Placebo/Cladribine Low Dose (PPLL)

Placebo/No Treatment

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: cladribine, cytarabine, venetoclax, and azacitidineExperimental Treatment4 Interventions

Participants will receive cladribine, cytarabine, and venetoclax for 2 cycles and then azacitidine and venetoclax for 2 cycles. Participants will repeat this pattern of 2 cycles each for up to a total of 18

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Cladribine

FDA approved

Cytarabine

FDA approved

Venetoclax

FDA approved

Azacitidine

FDA approved

0 / 13Eligibility criteria met

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

Cladribine, a purine nucleoside analog, interferes with DNA synthesis, leading to cell death, particularly in rapidly dividing cells like leukemic cells. Cytarabine, a cytosine nucleoside analog, also inhibits DNA synthesis by incorporating into DNA and preventing replication. Venetoclax, a BCL-2 inhibitor, promotes apoptosis by inhibiting the BCL-2 protein, which normally helps cancer cells survive. Azacitidine, a hypomethylating agent, incorporates into DNA and RNA, leading to hypomethylation and reactivation of tumor suppressor genes, thereby inhibiting cancer cell growth. These mechanisms are crucial for CMML patients as they target the abnormal proliferation and survival of leukemic cells, aiming to control the disease and improve patient outcomes.

Relationship between in vitro drug sensitivity and clinical response of patients to treatment in chronic lymphocytic leukemia.