Screening Tool for Myeloid Cancer

Recruiting at 301 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Cytarabine

Disqualifiers: Prior anti-cancer therapy, others

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

Compensation: Varies

Number of Visits: 2

Duration: Varies by treatment arm, typically 28-day cycles

2000 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This MyeloMATCH Master Screening and Reassessment Protocol (MSRP) evaluates the use of a screening tool and specific laboratory tests to help improve participants' ability to register to clinical trials throughout the course of their myeloid cancer (acute myeloid leukemia or myelodysplastic syndrome) treatment. This study involves testing patients' bone marrow and blood for certain biomarkers. A biomarker (sometimes called a marker) is any molecule in the body that can be measured. Doctors look at markers to learn what is happening in the body. Knowing about certain markers can give doctors more information about what is driving the cancer and how to treat it. Testing patients' bone marrow and blood will show doctors if patients have markers that specific drugs can target. The marker testing in this study will let doctors know if they can match patients with a treatment study (myeloMATCH clinical trial) that tests treatment for the type of cancer they have or continue standard of care treatment with their doctor on the Tier Advancement Pathway (TAP).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you must stop taking hydroxyurea within 24 hours before starting the treatment study or standard care pathway. Active hormonal therapy is allowed.

Is CPX-351 safe for treating myeloid cancer?

CPX-351, a combination of cytarabine and daunorubicin, has been shown to have an acceptable safety profile in treating acute myeloid leukemia (AML), with side effects similar to conventional chemotherapy. However, some patients experienced severe toxicities, including febrile neutropenia (fever with low white blood cell count), and one case of lethal toxicity was reported. ^{1 2 3 4 5}

How is the drug CPX-351 different from other treatments for myeloid cancer?

CPX-351 is unique because it combines two drugs, cytarabine and daunorubicin, in a special liposome (a tiny bubble made of fat) that keeps them at an optimal ratio, enhancing their ability to fight cancer cells more effectively than when used separately. This formulation allows for better targeting and prolonged exposure to the cancer cells, potentially leading to improved outcomes compared to traditional treatments. ^{4 5 6 7 8}

What data supports the effectiveness of the drug CPX-351 in treating myeloid cancer?

Research shows that CPX-351, a combination of cytarabine and daunorubicin in a liposomal form, has improved outcomes in patients with acute myeloid leukemia (AML) compared to traditional treatments. The drug maintains a specific ratio of its components, which enhances its ability to target and kill leukemia cells effectively. ^{4 6 8 9 10}

Who Is on the Research Team?

Jerald P Radich

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

This trial is for adults suspected to have untreated acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), without a history of other related blood disorders. Participants must be willing to submit bone marrow and blood specimens, consent to specimen banking, and sign an informed consent form.

Inclusion Criteria

I agree to submit specimens for the study.

I agree to have my samples stored for research.

I am suspected to have AML or MDS and have not been treated for it. I also have no history of MPN or MDS if considering an AML treatment study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Mutation Carrier Screening

Patients undergo bone marrow aspiration and collection of blood for rapid genetic testing to determine eligibility for specific treatment substudies or assignment to TAP.

Within 72 hours for initial therapy, 10 days for subsequent therapy

1 visit (in-person)

Treatment

Patients are assigned to a specific treatment substudy based on their mutational profile or continue with standard of care treatment under TAP.

Varies by treatment arm, typically 28-day cycles

Multiple visits (in-person) per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment, including bone marrow aspiration and blood collection.

6 months

Regular visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Azacitidine
• Biospecimen Collection
• Bone Marrow Aspiration
• Bone Marrow Aspiration and Biopsy
• Cytarabine
• Daunorubicin Hydrochloride
• Echocardiography
• Liposome-encapsulated Daunorubicin-Cytarabine
• Multigated Acquisition Scan
• Mutation Carrier Screening
• Venetoclax

Trial Overview The MyeloMATCH trial uses marker testing on patients' bone marrow and blood to match them with specific drug treatment trials targeting their cancer type or continue standard care. It includes various interventions like chemotherapy drugs, biopsies, scans, and biospecimen collection.

How Is the Trial Designed?

Group I: TAP (SOC treatment, mutation carrier screening) Experimental Treatment 2 Interventions

Patients continue SOC treatment and undergo continued bone marrow aspiration and blood collection for possible future substudy assignment.

Group II: Screening (mutation carrier screening) Experimental Treatment 1 Intervention

Patients undergo bone marrow aspiration and collection of blood on study. Patients' bone marrow and blood specimens undergo rapid genetic testing. Patients are then assigned to a specific substudy containing a therapy targeted to the patient's mutational profile. If there is no targetable mutation, the patient is placed on a substudy testing novel combinations that do not contain a target-specific drug. Patients who are not eligible for any MYELOMATCH substudy are assigned to TAP.

Group III: MM3TCT-A03 Maintenance I (venetoclax) Experimental Treatment 6 Interventions

Patients receive venetoclax PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 1 year post transplant (9 cycles) in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow biopsy and blood, urine and buccal swab collection throughout the study. Patients may also undergo PET scan and/or CT scan throughout the study.

Group IV: MM3TCT-A03 Conditioning 2A (haplo/mismatch with venetoclax) Experimental Treatment 12 Interventions

Patients receive venetoclax PO QD on days -10 to -2, melphalan IV on day -6, fludarabine IV on days -5 to -2 and undergo total body irradiation once on day -1. Patients then receive hematopoietic cell transplant IV on day 0. Treatment is given in the absence of disease progression or unacceptable toxicity. Patients undergo chest x-ray, echocardiography or MUGA during screening, and bone marrow biopsy and blood, urine and buccal swab collection throughout the study. Patients may also undergo PET scan and/or CT scan throughout the study.

Group V: MM3TCT-A03 Conditioning 1A (matched donors with venetoclax) Experimental Treatment 12 Interventions

Patients receive venetoclax PO QD on days -10 to -2, fludarabine IV on days -6 or -5 to -2 and busulfan IV on days -3 to -2 or BID on days -5 to -2 or melphalan IV on day -2. Patients then receive hematopoietic cell transplant IV on day 0. Treatment is given in the absence of disease progression or unacceptable toxicity. Patients undergo chest x-ray, echocardiography or MUGA during screening, and bone marrow biopsy and blood, urine and buccal swab collection throughout the study. Patients may also undergo PET scan and/or CT scan throughout the study.

Group VI: MM2YA-EA01 Arm D (azacitidine, venetoclax) Experimental Treatment 5 Interventions

Patients receive azacitidine IV or SC and venetoclax PO on study. Patients undergo bone marrow aspiration and biopsy on study. Patients may also undergo ECHO and/or MUGA as clinically indicated.

Group VII: MM2YA-EA01 Arm C (Vyxeos, venetoclax) Experimental Treatment 5 Interventions

Patients receive Vyxeos IV and venetoclax PO on study. Patients undergo bone marrow aspiration and biopsy on study. Patients may also undergo ECHO and/or MUGA as clinically indicated.

Group VIII: MM2YA-EA01 Arm B (cytarabine, venetoclax) Experimental Treatment 5 Interventions

Patients receive cytarabine IV and venetoclax PO on study. Patients undergo bone marrow aspiration and biopsy on study. Patients may also undergo ECHO and/or MUGA as clinically indicated.

Group IX: MM1YA-S01 Arm V (Vyxeos, venetoclax) Experimental Treatment 6 Interventions

Patients receive daunorubicin and cytarabine liposome IV over 90 minutes on days 1, 3, and 5 and venetoclax PO on days 1-14 of each cycle. Cycles repeat every 28 days for 1 cycle in the absence of disease progression or unacceptable toxicity. Patients may receive an additional cycle of daunorubicin and cytarabine liposome IV over 90 minutes on days 1 and 3 and venetoclax PO on days 1-7. Patients undergo ECHO or MUGA scan during screening. Patients also undergo a bone marrow aspiration and collection of blood throughout the trial.

Group X: MM1YA-S01 Arm IV (Vyxeos) Experimental Treatment 5 Interventions

Patients receive daunorubicin and cytarabine liposome IV over 90 minutes on days 1, 3, and 5 of each cycle. Cycles repeat every 28 days for 1 cycle in the absence of disease progression or unacceptable toxicity. Patients may receive an additional cycle of daunorubicin and cytarabine liposome IV over 90 minutes on days 1 and 3. Patients undergo ECHO or MUGA scan during screening. Patients also undergo a bone marrow aspiration and collection of blood throughout the trial.

Group XI: MM1YA-S01 Arm III (azacitidine, venetoclax) Experimental Treatment 6 Interventions

Patients receive azacitidine SC or IV on days 1-7 and venetoclax PO on days 1-28 of each cycle. Cycles repeat every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or MUGA scan during screening. Patients also undergo a bone marrow aspiration and collection of blood throughout the trial.

Group XII: MM1YA-S01 Arm II (cytarabine, daunorubicin, venetoclax) Experimental Treatment 7 Interventions

Patients receive cytarabine IV continuously on days 2-8 and daunorubicin IV on days 2-4 with venetoclax PO on days 1-11 of each cycle. Cycles repeat every 28 days for 1 cycle in the absence of disease progression or unacceptable toxicity. Patients may receive an additional cycle of cytarabine IV continuously on days 2-6 and daunorubicin IV on days 2-3 with venetoclax PO on days 1-8. Patients undergo ECHO or MUGA scan during screening. Patients also undergo a bone marrow aspiration and collection of blood throughout the trial.

Group XIII: MM1YA-CTG01 Arm II (azacitidine, venetoclax) Experimental Treatment 4 Interventions

Patients receive azacitidine IV or SC and venetoclax PO on study and undergo bone marrow aspiration and collection of blood samples on study and as clinically indicated.

Group XIV: MM1YA-CTG01 Arm I (daunorubicin, cytarabine, venetoclax) Experimental Treatment 5 Interventions

Patients receive daunorubicin IV, cytarabine IV, and venetoclax PO on study and undergo bone marrow aspiration and collection of blood samples on study and as clinically indicated.

Group XV: MM1YA-A04 Regimen 2 (venetoclax, chemotherapy) Experimental Treatment 9 Interventions

Patients receive gemtuzumab ozogamicin IV on days 1 and 4, cytarabine IV, continuously, on days 1-7 and daunorubicin IV on days 1-3 in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care consolidation/post-remission treatment at the discretion of the treating physician. Patients undergo echocardiography or MUGA scan during screening and bone marrow aspiration and biopsy and blood sample collection throughout the study. Patients may also undergo optional buccal swab collection throughout the study.

Group XVI: MM1OA-S03 Arm 2 (ASTX727, venetoclax, enasidenib) Experimental Treatment 6 Interventions

Patients receive ASTX727 PO QD on days 1-5, venetoclax PO QD on days 1-28, and enasidenib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, bone marrow aspiration, and bone marrow biopsy throughout the trial.

Group XVII: MM1OA-EA02 Regimen 3 (azacitidine, venetoclax, gilteritinib) Experimental Treatment 5 Interventions

INDUCTION: Patients receive azacitidine IV or SC on days 1-7 and venetoclax PO on days 1-28, and gilteritinib PO on days 8-21 of each cycle. Treatment repeats every 28 days for up to 2 cycles or until patient achieves remission, whichever comes first, in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients receive azacitidine IV or SC on days 1-5, venetoclax PO on days 1-14 and gilteritinib PO on days 8-21 of each cycle. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow biopsy and aspiration as well as blood sample collection on the trial.

Group XVIII: MM1OA-EA02 Regimen 2 (azacitidine, venetoclax, gilteritinib) Experimental Treatment 5 Interventions

INDUCTION: Patients receive azacitidine IV or SC on days 1-7 and venetoclax and gilteritinib PO on days 1-28 of each cycle. Treatment repeats every 28 days for up to 2 cycles or until patient achieves remission, whichever comes first, in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients receive azacitidine IV or SC on days 1-5, venetoclax PO on days 1-7 and gilteritinib PO on days 1-28 of each cycle. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow biopsy and aspiration as well as blood sample collection on the trial.

Group XIX: MM1OA-EA02 Regimen 1 (azacitidine, venetoclax) Experimental Treatment 4 Interventions

INDUCTION: Patients receive azacitidine IV or SC on days 1-7 of each cycle and venetoclax PO on days 1-28 of each cycle. Treatment repeats every 28 days for up to 2 cycles or until patient achieves remission, whichever comes first, in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients receive azacitidine IV or SC on days 1-7 and venetoclax PO on days 1-28 of each cycle. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow biopsy and aspiration as well as blood sample collection on the trial.

Group XX: MM1MDS-A01 Arm B (ASTX727, enasidenib) Experimental Treatment 4 Interventions

Patients receive ASTX727 PO QD on days 1-5 and enasidenib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience CR, PR, or SD any time after 4 cycles of treatment may be reassessed in order to go to a higher myeloMATCH tier assignment or to TAP. Patients also undergo bone marrow biopsy and aspiration throughout the study. Patients may also undergo optional buccal swab on study, and/or optional additional bone marrow aspiration and blood sample collection on study and at disease progression.

Group XXI: MM1MDS-A01 Arm A (ASTX727) Active Control 3 Interventions

Patients receive ASTX727 PO QD on days 1-5 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who do not achieve a CR, CRL, or CRh at the end of cycle 6 may cross-over to Arm B. Patients who experience CR, PR, or stable disease (SD) any time after 4 cycles of treatment may be reassessed in order to go to a higher myeloMATCH tier assignment or to TAP. Patients also undergo bone marrow biopsy and aspiration throughout the study. Patients may also undergo optional buccal swab on study, and/or optional additional bone marrow aspiration and blood sample collection on study and at disease progression.

Group XXII: MM1OA-S03 Arm 1 (ASTX727, venetoclax) Active Control 5 Interventions

Patients receive ASTX727 PO QD on days 1-5 and venetoclax PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, bone marrow aspiration, and bone marrow biopsy throughout the trial.

Group XXIII: MM1YA-A04 Regimen 1 (gemtuzumab ozogamicin, chemotherapy) Active Control 9 Interventions

Patients receive gemtuzumab ozogamicin IV on days 1 and 4, cytarabine IV, continuously, on days 1-7 and daunorubicin IV on days 1-3 in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care consolidation/post-remission treatment at the discretion of the treating physician. Patients undergo echocardiography or MUGA scan during screening and bone marrow aspiration and biopsy and blood sample collection throughout the study. Patients may also undergo optional buccal swab collection throughout the study.

Group XXIV: MM1YA-S01 Arm I (cytarabine, daunorubicin) Active Control 6 Interventions

Patients receive cytarabine IV continuously on days 1-7 and daunorubicin IV on days 1-3 per standard approach of each cycle. Cycles repeat every 28 days for 1 cycle in the absence of disease progression or unacceptable toxicity. Patients may receive an additional cycle of cytarabine IV continuously on days 1-5 and daunorubicin IV on days 1-2. Patients undergo ECHO or MUGA scan during screening. Patients also undergo a bone marrow aspiration and collection of blood throughout the trial.

Group XXV: MM2YA-EA01 Arm A (cytarabine) Active Control 4 Interventions

Patients receive cytarabine IV on study. Patients undergo bone marrow aspiration and biopsy on study. Patients may also undergo ECHO and/or MUGA as clinically indicated.

Group XXVI: MM1YA-CTG01 Arm III (daunorubicin, cytarabine) Active Control 4 Interventions

Patients receive daunorubicin IV and cytarabine IV on study and undergo bone marrow aspiration and collection of blood samples on study and as clinically indicated.

Group XXVII: MM3TCT-A03 Conditioning 1B (matched donors with placebo) Placebo Group 12 Interventions

Patients receive placebo PO QD on days -10 to -2, fludarabine IV on days -6 or -5 to -2 and busulfan IV on days -3 to -2 or BID on days -5 to -2 or melphalan IV on day -2. Patients then receive hematopoietic cell transplant IV on day 0. Treatment is given in the absence of disease progression or unacceptable toxicity. Patients undergo chest x-ray, echocardiography or MUGA during screening, and bone marrow biopsy and blood, urine and buccal swab collection throughout the study. Patients may also undergo PET scan and/or CT scan throughout the study.

Group XXVIII: MM3TCT-A03 Conditioning 2B (haplo/mismatch with placebo) Placebo Group 11 Interventions

Patients receive placebo PO QD on days -10 to -2, melphalan IV on day -6, fludarabine IV on days -5 to -2 and undergo total body irradiation once on day -1. Patients then receive hematopoietic cell transplant IV on day 0. Treatment is given in the absence of disease progression or unacceptable toxicity. Patients undergo chest x-ray, echocardiography or MUGA during screening, and bone marrow biopsy and blood, urine and buccal swab collection throughout the study. Patients may also undergo PET scan and/or CT scan throughout the study.

Group XXIX: MM3TCT-A03 Maintenance II (placebo) Placebo Group 5 Interventions

Patients receive placebo PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 1 year post transplant (9 cycles) in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow biopsy and blood, urine and buccal swab collection throughout the study. Patients may also undergo PET scan and/or CT scan throughout the study.

Azacitidine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Vidaza for:

• Acute myeloid leukemia
• Chronic myelomonocytic leukemia
• Myelodysplastic syndromes

Approved in United States as Vidaza for:

• Myelodysplastic syndromes
• Chronic myelomonocytic leukemia

Approved in Canada as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Approved in Japan as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a phase II study involving 125 patients with acute myeloid leukemia (AML) in first relapse, CPX-351 showed improved response rates and lower 60-day mortality in patients classified as poor-risk according to the European Prognostic Index.

While CPX-351 did not meet the overall statistical criteria for 1-year survival improvement compared to standard salvage chemotherapy, it demonstrated significant benefits in event-free survival and overall survival for the poor-risk subgroup, suggesting it may be a more effective treatment option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II, multicenter, randomized trial of CPX-351 (cytarabine:daunorubicin) liposome injection versus intensive salvage therapy in adults with first relapse AML. Cortes, JE., Goldberg, SL., Feldman, EJ., et al.[2021]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

CPX-351, a liposome formulation of cytarabine and daunorubicin, demonstrated potent anti-leukemic activity in a mouse model, effectively reducing leukemia cells in bone marrow to undetectable levels for weeks, unlike the free-drug cocktail which only provided temporary suppression.

The enhanced efficacy of CPX-351 is attributed to its ability to deliver higher concentrations of the drugs directly to leukemia cells, leading to prolonged exposure and selective killing of these cells, while causing similar levels of myelosuppression as the free-drug cocktail.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Leukemia-selective uptake and cytotoxicity of CPX-351, a synergistic fixed-ratio cytarabine:daunorubicin formulation, in bone marrow xenografts. Lim, WS., Tardi, PG., Dos Santos, N., et al.[2022]

CPX-351 (Vyxeos®) is a dual-drug liposomal formulation of cytarabine and daunorubicin designed to improve efficacy in treating acute myeloid leukemia (AML) by maintaining a synergistic 5:1 drug ratio, which enhances its effectiveness compared to traditional chemotherapy regimens.

The liposomal encapsulation allows for controlled release and preferential uptake by malignant cells, which helps to protect the drugs from metabolism and reduces exposure to off-target tissues, contributing to a favorable safety profile while effectively targeting leukemia cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CPX-351: a nanoscale liposomal co-formulation of daunorubicin and cytarabine with unique biodistribution and tumor cell uptake properties. Mayer, LD., Tardi, P., Louie, AC.[2020]

In a study involving 53 AML patients, CPX-351 demonstrated significant cytotoxic activity, particularly in cases with the FLT3-ITD mutation, which were five times more sensitive to the treatment.

The effectiveness of CPX-351 was consistent across various leukemia types, with its cellular uptake correlating with its cytotoxic potency, suggesting that ex vivo testing could help identify AML patients who would benefit most from this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CPX-351 exhibits potent and direct ex vivo cytotoxicity against AML blasts with enhanced efficacy for cells harboring the FLT3-ITD mutation. Gordon, MJ., Tardi, P., Loriaux, MM., et al.[2018]

VYXEOS™, a liposomal formulation of daunorubicin and cytarabine, has been shown to significantly improve overall survival and event-free survival in older patients with newly diagnosed high-risk acute myeloid leukaemia (AML) compared to conventional chemotherapy (7+3).

The treatment also resulted in higher rates of complete remission and was well-tolerated, with a safety profile similar to that of the standard chemotherapy regimen, making it a valuable option for patients with therapy-related AML or AML with myelodysplasia-related changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daunorubicin/Cytarabine Liposome: A Review in Acute Myeloid Leukaemia. Blair, HA.[2020]

In a study of 9 adult AML patients treated with liposomal CPX-351, the overall response rate was 75%, but 56% experienced severe non-hematological toxicities, indicating a significant safety concern associated with the treatment.

The study found that patients with poor metabolizer (PM) status for cytidine deaminase (CDA) had much higher levels of cytarabine in their system, leading to prolonged exposure and reduced clearance, which suggests that CDA status significantly affects the pharmacokinetics and safety of CPX-351.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacogenetics of liposomal cytarabine in AML patients treated with CPX-351. Donnette, M., Hamimed, M., Ciccolini, J., et al.[2021]

The VA regimen, combining venetoclax and azacitidine, demonstrated a high complete remission (cCR) rate of 78.8% after the first treatment cycle and 81.8% after prolonged treatment in 66 patients with newly diagnosed acute myeloid leukemia (AML) who were not suitable for conventional chemotherapy.

The treatment was generally safe, with manageable adverse effects, primarily neutropenia, thrombocytopenia, and anemia, and showed better outcomes in patients with specific gene mutations (IDH1/2 or NPM1) and those experiencing rebound thrombocytosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy of venetoclax combined azacitidine in newly diagnosed acute myeloid leukemia unfit for standard chemotherapy: a single center experience]. Sun, L., Ye, SJ., Zhou, N., et al.[2023]

CPX-351, a liposomal formulation of cytarabine and daunorubicin, shows superior cytotoxicity compared to standard daunorubicin and cytarabine combinations in cytarabine-resistant leukemia cells, indicating its potential effectiveness in treating high-risk acute myeloid leukemia (AML).

In primary AML patient samples, CPX-351 demonstrated a rapid increase in intracellular ara-CTP levels, particularly in patients who later experienced treatment failure, suggesting that Flu-CPX may improve patient outcomes by enhancing drug activation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CPX-351 exhibits hENT-independent uptake and can be potentiated by fludarabine in leukaemic cells lines and primary refractory AML. Anderson, E., Mehta, P., Heywood, J., et al.[2022]

CPX-351, a liposomal formulation of cytarabine and daunorubicin, shows improved safety and efficacy in treating acute myeloid leukemia by providing prolonged tissue exposure and altered distribution compared to traditional non-liposomal combinations.

Preclinical studies indicate that CPX-351 maintains similar drug release and metabolism patterns as the standard treatment but results in lower unbound plasma concentrations, which may contribute to its enhanced therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, drug metabolism, and tissue distribution of CPX-351 in animals. Wang, Q., Tardi, P., Sadowski, N., et al.[2021]

Citations

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

Phase II, multicenter, randomized trial of CPX-351 (cytarabine:daunorubicin) liposome injection versus intensive salvage therapy in adults with first relapse AML. [2021]

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

Efficacy of CPX-351, (cytarabine:daunorubicin) liposome injection, against acute lymphoblastic leukemia (ALL) xenograft models of the Pediatric Preclinical Testing Program. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Leukemia-selective uptake and cytotoxicity of CPX-351, a synergistic fixed-ratio cytarabine:daunorubicin formulation, in bone marrow xenografts. [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

CPX-351: a nanoscale liposomal co-formulation of daunorubicin and cytarabine with unique biodistribution and tumor cell uptake properties. [2020]

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

CPX-351 exhibits potent and direct ex vivo cytotoxicity against AML blasts with enhanced efficacy for cells harboring the FLT3-ITD mutation. [2018]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Daunorubicin/Cytarabine Liposome: A Review in Acute Myeloid Leukaemia. [2020]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacogenetics of liposomal cytarabine in AML patients treated with CPX-351. [2021]

8. China pubmed.ncbi.nlm.nih.gov

[Efficacy of venetoclax combined azacitidine in newly diagnosed acute myeloid leukemia unfit for standard chemotherapy: a single center experience]. [2023]

9. England pubmed.ncbi.nlm.nih.gov

CPX-351 exhibits hENT-independent uptake and can be potentiated by fludarabine in leukaemic cells lines and primary refractory AML. [2022]

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

Pharmacokinetics, drug metabolism, and tissue distribution of CPX-351 in animals. [2021]