60 Participants Needed

CPX-351 vs CLAG-M for Acute Myeloid Leukemia

Roland Walter, MD profile photo
Overseen ByRoland Walter, MD
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: Fred Hutchinson Cancer Research Center
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This phase II trial studies how well CPX-351 or the CLAG-M regimen (consisting of the drugs cladribine, cytarabine, G-CSF, and mitoxantrone) works in treating medically less-fit patients with acute myeloid leukemia or other high-grade myeloid neoplasms. Drugs used in chemotherapy, such as CPX-351, cladribine, cytarabine, G-CSF, and mitoxantrone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving CPX-351 or the CLAG-M regimen at doses typically used for medically-fit patients with acute myeloid leukemia may work better than reduced doses of CPX-351 in treating medically less-fit patients with acute myeloid leukemia or other high-grade myeloid neoplasms.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must stop hydroxyurea before starting the study treatment. If you are on a FLT3-inhibitor for FLT3-mutated AML, you can continue that treatment.

Is CPX-351 generally safe for humans?

CPX-351, a combination of cytarabine and daunorubicin, has been studied for safety in humans and animals. It was approved by the FDA for certain types of acute myeloid leukemia (AML) and has shown a favorable safety profile compared to traditional treatments, with lower unbound drug concentrations in the body, which may reduce side effects.12345

What makes the drug CPX-351 unique for treating acute myeloid leukemia?

CPX-351 is unique because it combines two drugs, cytarabine and daunorubicin, in a special liposomal form that delivers them in a fixed 5:1 ratio directly to leukemia cells, improving survival rates compared to the traditional 7+3 regimen. This formulation allows for better targeting of leukemia cells while maintaining a similar safety profile.12678

What data supports the effectiveness of the drug CPX-351 for treating acute myeloid leukemia?

CPX-351, a combination of cytarabine and daunorubicin, has shown improved survival rates and higher remission rates in older patients with secondary acute myeloid leukemia compared to the traditional '7+3' regimen. It was approved by the FDA for its effectiveness in treating newly diagnosed therapy-related AML and AML with myelodysplasia-related changes.1491011

Who Is on the Research Team?

Walter | Division of Hematology & Oncology

Roland Walter, MD

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

This trial is for less-fit patients with untreated high-grade myeloid neoplasms or AML, excluding acute promyelocytic leukemia. Participants must have a specific risk score (TRM >= 13.1), agree to use contraception, and be able to consent. Prior low-intensity treatments are allowed; significant liver function and heart health are required.

Inclusion Criteria

My bilirubin levels are below 2.0 mg/mL, or higher for specific medical reasons.
Ability to understand and the willingness to sign a written informed consent document
I have used hydroxyurea but will stop before the study starts. I may have had treatments for high WBC or tumor complications.
See 5 more

Exclusion Criteria

I have a severe form of leukemia and cannot be treated with tyrosine kinase inhibitors.
You have a known allergy or extreme sensitivity to any of the drugs being used in this study.
I have an infection, but it is being treated or is under control.
See 3 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Patients receive CPX-351 or CLAG-M regimen. CPX-351 is administered IV over 90 minutes on days 1, 3, and 5. CLAG-M includes cladribine, cytarabine, G-CSF, and mitoxantrone administered over several days.

1-2 weeks
Multiple visits for IV administration

Post-Remission Treatment

Patients achieving CR/CRi receive additional courses of reduced or intermediate doses of CPX-351 or cytarabine.

Up to 4 additional courses

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

  • Cladribine
  • Cytarabine
  • Liposome-encapsulated Daunorubicin-Cytarabine
  • Mitoxantrone
  • Recombinant Granulocyte Colony-Stimulating Factor
Trial Overview The study compares CPX-351 chemotherapy against the CLAG-M regimen in treating medically less-fit patients with certain types of blood cancer. It aims to determine if full doses used for fitter patients could be more effective than reduced doses in this population.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Group I: Arm II (CLAG-M)Experimental Treatment6 Interventions
Group II: Arm I (CPX-351)Experimental Treatment3 Interventions

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

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Approved in United States as Leustatin for:
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Approved in European Union as Litak for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

Fred Hutchinson Cancer Research Center

Lead Sponsor

Trials
444
Recruited
148,000+

Fred Hutchinson Cancer Center

Lead Sponsor

Trials
583
Recruited
1,341,000+

Jazz Pharmaceuticals

Industry Sponsor

Trials
252
Recruited
35,100+
Bruce C. Cozadd profile image

Bruce C. Cozadd

Jazz Pharmaceuticals

Chief Executive Officer since 2009

BA in Economics from Yale University, MBA from Stanford University

Dr. Austin profile image

Dr. Austin

Jazz Pharmaceuticals

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Published Research Related to This Trial

CPX-351, a liposomal-encapsulated combination of daunorubicin and cytarabine, has been approved for treating therapy-related acute myeloid leukemia (tAML) and AML with myelodysplasia-related changes (AML-MRCs), showing improved overall survival and remission rates in older patients compared to the traditional '7 + 3' treatment.
In a Phase III trial involving patients aged 60-75, CPX-351 demonstrated higher rates of complete remission and event-free survival, suggesting that its fixed 5:1 drug ratio may enhance efficacy in these challenging subgroups of AML.
Reformulating acute myeloid leukemia: liposomal cytarabine and daunorubicin (CPX-351) as an emerging therapy for secondary AML.Chen, EC., Fathi, AT., Brunner, AM.[2020]
CPX-351, a liposomal formulation of cytarabine and daunorubicin, showed high efficacy in treating childhood acute lymphoblastic leukemia (ALL) xenograft models, achieving complete responses in four B-lineage models and a partial response in one T-lineage model.
The drug was administered at a dose that resulted in plasma drug exposures similar to those seen in patients with acute myeloid leukemia (AML), indicating its potential effectiveness and safety for use in pediatric leukemia treatment.
Efficacy of CPX-351, (cytarabine:daunorubicin) liposome injection, against acute lymphoblastic leukemia (ALL) xenograft models of the Pediatric Preclinical Testing Program.Carol, H., Fan, MM., Harasym, TO., et al.[2021]
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.
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]

Citations

Reformulating acute myeloid leukemia: liposomal cytarabine and daunorubicin (CPX-351) as an emerging therapy for secondary AML. [2020]
Efficacy of CPX-351, (cytarabine:daunorubicin) liposome injection, against acute lymphoblastic leukemia (ALL) xenograft models of the Pediatric Preclinical Testing Program. [2021]
Improved outcome of children with relapsed/refractory acute myeloid leukemia by addition of cladribine to re-induction chemotherapy. [2021]
CPX-351 exhibits potent and direct ex vivo cytotoxicity against AML blasts with enhanced efficacy for cells harboring the FLT3-ITD mutation. [2018]
CPX-351 daunorubicin-cytarabine liposome: a novel formulation to treat patients with newly diagnosed secondary acute myeloid leukemia. [2020]
Pharmacokinetics, drug metabolism, and tissue distribution of CPX-351 in animals. [2021]
CPX-351 exhibits hENT-independent uptake and can be potentiated by fludarabine in leukaemic cells lines and primary refractory AML. [2022]
Phase I/II Study of CPX-351 Followed by Fludarabine, Cytarabine, and Granulocyte-Colony Stimulating Factor for Children With Relapsed Acute Myeloid Leukemia: A Report From the Children's Oncology Group. [2021]
Quality-adjusted Time Without Symptoms of disease or Toxicity (Q-TWiST) analysis of CPX-351 versus 7 + 3 in older adults with newly diagnosed high-risk/secondary AML. [2021]
10.United Statespubmed.ncbi.nlm.nih.gov
CPX-351 (cytarabine and daunorubicin) Liposome for Injection Versus Conventional Cytarabine Plus Daunorubicin in Older Patients With Newly Diagnosed Secondary Acute Myeloid Leukemia. [2022]
Leukemia-selective uptake and cytotoxicity of CPX-351, a synergistic fixed-ratio cytarabine:daunorubicin formulation, in bone marrow xenografts. [2022]
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