CLAG-GO for Acute Myeloid Leukemia

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Vu H Duong, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Maryland, Baltimore

Must not be taking: Gemtuzumab, Cladribine

Disqualifiers: CNS AML, Active infection, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial uses a combination of four drugs, including Bisantrene, to treat adult patients with a specific type of leukemia that hasn't responded to standard treatments or has returned. Bisantrene, a new drug, has shown effectiveness in early tests with manageable side effects. The treatment works by killing cancer cells and boosting the body's ability to fight infections.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications. However, any systemic chemotherapy and radiotherapy must be completed at least 7 days before starting the trial, except for hydroxyurea or 6-mercaptopurine, which must be stopped 24 hours before starting the trial.

What data supports the idea that CLAG-GO for Acute Myeloid Leukemia is an effective drug?

The available research shows that the CLAG-M regimen, which includes cladribine, cytarabine, mitoxantrone, and G-CSF, is effective for treating refractory acute myeloid leukemia. In one study, 49% of patients achieved complete remission, which means their cancer symptoms disappeared. This is a significant result compared to many other treatments. Additionally, the one-year survival rate for patients who achieved complete remission was 73%, indicating that the drug helps patients live longer. Although there are some side effects, the treatment's effectiveness makes it a promising option for those with difficult-to-treat leukemia. ^{1 2 3 4 5}

What safety data is available for the CLAG-GO treatment in acute myeloid leukemia?

The CLAG-GO treatment, which includes cladribine, cytarabine, G-CSF, and gemtuzumab ozogamicin, has been evaluated in several studies. The CLAG regimen, without gemtuzumab ozogamicin, showed hematologic toxicity as the most prominent side effect, but the overall toxicity was considered acceptable. Gemtuzumab ozogamicin, when used in combination with other drugs, has been associated with side effects such as hemorrhage, infection, veno-occlusive disease, and increased hepatotoxicity. However, it has shown significant antileukemia activity and improved survival rates in patients with acute myeloid leukemia. ^{1 2 4 6 7}

Is the drug combination of Cladribine, Cytarabine, Gemtuzumab Ozogamicin, and G-CSF promising for treating Acute Myeloid Leukemia?

Yes, the drug combination shows promise for treating Acute Myeloid Leukemia, especially in patients who have not responded to other treatments or have relapsed. Studies indicate that this combination can lead to complete remission in a significant number of patients, and it has been found to be more effective than many other treatments. The results are encouraging, with a good number of patients achieving remission and improved survival rates. ^{1 3 4 5 8}

Research Team

Vu H Duong, MD

Principal Investigator

University of Maryland Greenebaumn Comprehensive Cancer Center

Eligibility Criteria

This trial is for adults with AML that hasn't improved after standard chemo or has come back. They must have had at least one intensive chemo treatment, be in good physical shape, and not pregnant or fathering children during the study. People can't join if they have certain types of leukemia, active infections, other cancers unless cured over 3 years ago, severe heart problems, mental health issues affecting compliance, or previous specific treatments for AML.

Inclusion Criteria

I had a stem cell transplant over 60 days ago, have mild or no graft versus host disease, and haven't been on immunosuppressants for 2 weeks.

I finished any chemotherapy or radiotherapy at least a week ago, except for specific drugs for lowering blood cell counts.

I am a man who can father children and will use birth control during and for 3 months after treatment.

Exclusion Criteria

I have a history of VOD/SOS.

I do not have an active infection, or it is controlled with medication.

I have acute promyelocytic leukemia or chronic myelogenous leukemia in blast phase.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Induction Chemotherapy

Participants receive induction chemotherapy with CLAG-GO for 4-5 weeks

4-5 weeks

Hospitalized for treatment

Consolidation Therapy

Participants may receive a single cycle of consolidation therapy using the CLAG-GO regimen

4 weeks

Outpatient visits

Maintenance Therapy

Participants who remain in remission may receive up to 8 cycles of outpatient maintenance therapy

Up to 8 months

Monthly outpatient visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Regular follow-up visits

Treatment Details

Interventions

• Cladribine (Anti-tumor antibiotic)
• Cytarabine (Anti-metabolites)
• Gemtuzumab Ozogamicin (Monoclonal Antibodies)
• Granulocyte-Colony Stimulating Factor (Growth Factor)

Trial Overview The CLAG-GO trial tests a combo of chemotherapy drugs (cladribine, cytarabine, G-CSF and gemtuzumab ozogamicin) on patients with tough cases of AML. Participants will receive induction therapy in hospital followed by possible consolidation therapy or bone marrow transplant if remission occurs. Maintenance therapy may follow for those remaining in remission.

Participant Groups

Group I: CLAG-GO Experimental Treatment 1 Intervention

Cladribine, Cytarabine, and Granulocyte-Colony Stimulating Factor with Fractionated Gemtuzumab Ozogamicin (CLAG-GO)

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Dr. Mohan Suntha

University of Maryland, Baltimore

Chief Executive Officer since 2019

MD from Jefferson Medical College, MBA from Wharton School of Business, BA from Brown University

Dr. Taofeek K. Owonikoko

University of Maryland, Baltimore

Chief Medical Officer

MD, PhD

Hematologics, Inc

Collaborator

Trials

1

Recruited

40+

Findings from Research

The CLAG regimen, which includes cladribine, cytarabine, and G-CSF, demonstrated significant anti-leukemic activity in refractory acute myeloid leukemia (AML), achieving a complete remission (CR) rate of 50% in a study of 58 patients.

Hematologic toxicity was the most common side effect observed, but the regimen was considered to have an acceptable safety profile, with a 1-year overall survival rate of 42% for all patients and 65% for those who achieved CR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter, open, non-comparative, phase II study of the combination of cladribine (2-chlorodeoxyadenosine), cytarabine, and G-CSF as induction therapy in refractory acute myeloid leukemia - a report of the Polish Adult Leukemia Group (PALG). Wrzesień-Kuś, A., Robak, T., Lech-Marańda, E., et al.[2019]

In a study of 142 patients with CD33-positive acute myeloid leukemia (AML) in first relapse, 30% achieved remission after treatment with Mylotarg (gemtuzumab ozogamicin), indicating its efficacy as a targeted chemotherapy agent.

While Mylotarg was associated with some adverse effects, such as myelosuppression and elevated liver enzymes, it had a favorable safety profile overall, with low incidences of severe nausea, vomiting, and no significant cardiotoxicity or hair loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse. Sievers, EL., Larson, RA., Stadtmauer, EA., et al.[2022]

The CLAG regimen demonstrated a high efficacy in treating refractory or relapsed acute myeloid leukemia (AML), achieving a hematological complete response (CR) in 78.8% of patients, with a notably higher CR rate of 93.8% in relapsed patients compared to 64.7% in refractory patients.

Despite its effectiveness, the treatment was associated with significant adverse effects, including grade 4 neutropenia and thrombocytopenia, leading to infections in all patients, highlighting the critical need for infection control during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and safety analysis of the combination of cladribine, cytarabine, granulocyte colonystimulating factor (CLAG) regime in patients with refractory or relapsed acute myeloid leukemia]. Duan, MH., Zhang, Y., Zhang, M., et al.[2020]

The CLAG-M regimen, which includes cladribine, cytarabine, mitoxantrone, and G-CSF, demonstrated significant antileukemia activity in refractory acute myeloid leukemia (AML), achieving a complete remission (CR) rate of 49% among 43 patients studied.

The treatment showed an overall survival rate of 43% and a disease-free survival rate of 68.6% at one year, indicating its efficacy while maintaining acceptable levels of hematologic toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter, open, noncomparative, phase II study of the combination of cladribine (2-chlorodeoxyadenosine), cytarabine, granulocyte colony-stimulating factor and mitoxantrone as induction therapy in refractory acute myeloid leukemia: a report of the Polish Adult Leukemia Group. Wrzesień-Kuś, A., Robak, T., Wierzbowska, A., et al.[2013]

In a multi-center phase II study involving 118 patients with poor risk refractory or relapsed acute myeloid leukemia (AML), the CLAG-M salvage regimen resulted in a complete response (CR) rate of 58%, demonstrating its efficacy in this challenging patient population.

The treatment was generally well-tolerated, although hematological toxicity was the most common side effect, and the overall survival rate at 4 years was 14%, indicating that while effective, long-term outcomes remain a concern for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cladribine combined with high doses of arabinoside cytosine, mitoxantrone, and G-CSF (CLAG-M) is a highly effective salvage regimen in patients with refractory and relapsed acute myeloid leukemia of the poor risk: a final report of the Polish Adult Leukemia Group. Wierzbowska, A., Robak, T., Pluta, A., et al.[2013]

Gemtuzumab ozogamicin (Mylotarg) has been approved for treating acute myeloid leukemia (AML) in patients aged 15 and older, showing significant improvements in event-free survival and reduced relapse risk based on a meta-analysis of 3,325 patients.

While Mylotarg is effective, it is associated with common side effects such as hemorrhage and infection, particularly when used in combination with other chemotherapy drugs like daunorubicin and cytarabine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The EMA Review of Mylotarg (Gemtuzumab Ozogamicin) for the Treatment of Acute Myeloid Leukemia. Ali, S., Dunmore, HM., Karres, D., et al.[2020]

Gemtuzumab ozogamicin (Mylotarg) is an effective treatment for relapsed acute myeloid leukemia (AML), targeting CD33 on leukemic cells and using a potent cytotoxic agent to induce cell death, with promising results from early phase I/II studies.

While it shows significant efficacy, there are concerns about potential adverse effects, including veno-occlusive disease and increased liver toxicity, which are important considerations as it is being tested in new patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early phase I/II trials with gemtuzumab ozogamicin (Mylotarg) in acute myeloid leukemia. Nabhan, C., Tallman, MS.[2019]

In a study of 55 children with relapsed/refractory acute myeloid leukemia (R/R-AML), the CLAG-M treatment showed an overall response rate of 80%, significantly outperforming the MEC/IEC treatment, which had a response rate of 51%.

CLAG-M also resulted in better overall survival (66.8% vs. 40.4%) and progression-free survival (52.6% vs. 34.9%) at 3 years compared to MEC/IEC, particularly benefiting low-risk patients, while those with the FLT3-ITD mutation had poorer outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved outcome of children with relapsed/refractory acute myeloid leukemia by addition of cladribine to re-induction chemotherapy. Ruan, M., Liu, LP., Zhang, AL., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

A multicenter, open, non-comparative, phase II study of the combination of cladribine (2-chlorodeoxyadenosine), cytarabine, and G-CSF as induction therapy in refractory acute myeloid leukemia - a report of the Polish Adult Leukemia Group (PALG). [2019]

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

Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse. [2022]

3. China pubmed.ncbi.nlm.nih.gov

[Efficacy and safety analysis of the combination of cladribine, cytarabine, granulocyte colonystimulating factor (CLAG) regime in patients with refractory or relapsed acute myeloid leukemia]. [2020]

4. Germany pubmed.ncbi.nlm.nih.gov

A multicenter, open, noncomparative, phase II study of the combination of cladribine (2-chlorodeoxyadenosine), cytarabine, granulocyte colony-stimulating factor and mitoxantrone as induction therapy in refractory acute myeloid leukemia: a report of the Polish Adult Leukemia Group. [2013]

5. England pubmed.ncbi.nlm.nih.gov

Cladribine combined with high doses of arabinoside cytosine, mitoxantrone, and G-CSF (CLAG-M) is a highly effective salvage regimen in patients with refractory and relapsed acute myeloid leukemia of the poor risk: a final report of the Polish Adult Leukemia Group. [2013]

6. England pubmed.ncbi.nlm.nih.gov

The EMA Review of Mylotarg (Gemtuzumab Ozogamicin) for the Treatment of Acute Myeloid Leukemia. [2020]

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

Early phase I/II trials with gemtuzumab ozogamicin (Mylotarg) in acute myeloid leukemia. [2019]

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

Improved outcome of children with relapsed/refractory acute myeloid leukemia by addition of cladribine to re-induction chemotherapy. [2021]