CLAG-GO for Acute Myeloid Leukemia

Recruiting at 2 trial locations

Overseen By Oyinkansola Arasanmi

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Maryland, Baltimore

Must not be taking: Gemtuzumab, Cladribine

Disqualifiers: CNS AML, Active infection, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

39 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of chemotherapy drugs to treat acute myeloid leukemia (AML) that has not responded to standard treatments or has returned after remission. The focus is on a mix of drugs called CLAG-GO, which includes Cladribine, Cytarabine, Gemtuzumab Ozogamicin, and Granulocyte-Colony Stimulating Factor. This combination aims to help individuals whose AML is stubborn or has relapsed. It suits those who have previously tried intensive chemotherapy without success and meet certain health requirements. Participants will spend about 4-5 weeks in the hospital for the initial treatment and may receive further therapies depending on their response. The goal is to determine if this new drug combination can better manage AML and explore its effects in the body. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research has shown that the CLAG-GO treatment, a combination of chemotherapy drugs, has been tested for safety in people with leukemia. This mix includes cladribine, cytarabine, a growth factor called G-CSF, and gemtuzumab ozogamicin, and is generally well-tolerated. However, like all treatments, it can have side effects.

In earlier studies, patients experienced common chemotherapy side effects, such as low blood cell counts, fever, and a higher risk of infections. These side effects are typical for leukemia treatments. Importantly, past research has carefully examined the frequency and severity of these side effects.

Researchers closely monitored participants in the studies, which helped manage any side effects. The treatment has also been used in other situations, providing more safety information. Overall, while CLAG-GO might cause some discomfort, it is considered manageable with medical supervision. ^{1 2 3 4 5}

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

Unlike the standard treatments for Acute Myeloid Leukemia (AML), which often include chemotherapy drugs and stem cell transplants, the CLAG-GO combination therapy offers a unique approach. It incorporates Cladribine and Cytarabine with Gemtuzumab Ozogamicin, an antibody-drug conjugate that specifically targets leukemia cells, potentially reducing damage to healthy cells. Additionally, the inclusion of Granulocyte-Colony Stimulating Factor (G-CSF) helps boost the body's production of white blood cells, speeding up recovery and strengthening the immune response. Researchers are excited about CLAG-GO because it combines targeted therapy with immune support, potentially leading to more effective and less toxic outcomes for AML patients.

What evidence suggests that CLAG-GO could be an effective treatment for acute myeloid leukemia?

Studies have shown that the CLAG-GO combination can effectively treat acute myeloid leukemia (AML), particularly when the disease resists standard treatments or returns after remission. This trial will evaluate the CLAG-GO regimen, which combines cladribine, cytarabine, and a growth factor with gemtuzumab ozogamicin. Research indicates that this combination has led to remission in some patients. Specifically, CLAG-GO has proven to be a favorable option compared to other similar treatments, showing promising results in patients whose AML has returned or not responded to other treatments. Initial findings suggest that this combination can help achieve remission with manageable side effects. Overall, the evidence supports CLAG-GO as a beneficial treatment option for those struggling with AML. ^{1 2 4 5 6}

Who Is on the Research Team?

Vu H Duong, MD

Principal Investigator

University of Maryland Greenebaumn Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Cladribine
• Cytarabine
• Gemtuzumab Ozogamicin
• Granulocyte-Colony Stimulating 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.

How Is the Trial Designed?

Group I: CLAG-GO Experimental Treatment 1 Intervention

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

Cladribine is already approved in United States, European Union for the following indications:

Approved in United States as Leustatin for:

• Hairy cell leukemia
• Chronic lymphocytic leukemia (CLL)
• Non-Hodgkin's lymphoma
• Multiple sclerosis

Approved in European Union as Litak for:

• Hairy cell leukemia
• Chronic lymphocytic leukemia (CLL)
• Non-Hodgkin's lymphoma

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Hematologics, Inc

Collaborator

Trials

1

Recruited

40+

Published Research Related to This Trial

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]

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]

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) 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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03531918?cond=%22Leukemia%22&intr=%222-chloro-3'-deoxyadenosine%22&viewType=Table&rank=7

Gemtuzumab Ozogamicin With G-CSF, Cladribine, Cytarabine & ... This phase I/II trial studies the side effects and best dosing frequency of gemtuzumab ozogamicin when given in combination with granulocyte colony ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04050280?term=AREA%5BBasicSearch%5D(clag)&rank=8

CLAG-GO for Patients With Persistent, Relapsed or ... This study involves evaluating a combination of chemotherapy drugs known as " CLAG -GO" [cladribine, cytarabine, granulocyte-colony stimulating factor ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5996008/

Comparison of clinical remission and survival between CLAG ... CLAG was equally effective to FLAG induction chemotherapy in total R/R AML patients, while CLAG seemed to be a better option than FLAG in patients with ...

4. researchgate.net researchgate.net/publication/397130807_Cladribine_high-dose_cytarabine_plus_gemtuzumab_ozogamicin_CLAG-GO_as_frontline_intensive_therapy_for_fit_patients_with_core-binding_factor_acute_myeloid_leukemia

Cladribine, high-dose cytarabine, plus gemtuzumab ... Background: The combination of intermediate-dose cytarabine plus mitoxantrone (IMA) can induce high complete remission rates with acceptable toxicity in elderly ...

5. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT03531918/

Clinical Trial: NCT03531918 This phase I/II trial studies the side effects and best dosing frequency of gemtuzumab ozogamicin when given in combination with granulocyte ...

6. researchgate.net researchgate.net/publication/397130807_Cladribine_high-dose_cytarabine_plus_gemtuzumab_ozogamicin_CLAG-GO_as_frontline_intensive_therapy_for_fit_patients_with_core-binding_factor_acute_myeloid_leukemia?_tp=eyJjb250ZXh0Ijp7InBhZ2UiOiJqb3VybmFsIiwicHJldmlvdXNQYWdlIjpudWxsLCJzdWJQYWdlIjoib3ZlcnZpZXcifX0

Cladribine, high-dose cytarabine, plus gemtuzumab ... Purpose To evaluate safety, tolerability, potential efficacy, and pharmacodynamics (PD) of zosuquidar (Zos) in combination with gemtuzumab ozogamicin (GO) in ...