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.
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.12345
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.16789
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.123910
Research Team
JP
Jerald P Radich
Principal Investigator
SWOG Cancer Research Network
Eligibility Criteria
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.
See 4 more
Trial Timeline
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.
Trial OverviewThe 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.
Participant Groups
23Treatment groups
Experimental Treatment
Active Control
Group I: TAP (SOC treatment, mutation carrier screening)Experimental Treatment2 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 Treatment1 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: MM2YA-EA01 Arm D (azacitidine, venetoclax)Experimental Treatment5 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 IV: MM2YA-EA01 Arm C (Vyxeos, venetoclax)Experimental Treatment5 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 V: MM2YA-EA01 Arm B (cytarabine, venetoclax)Experimental Treatment5 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 VI: MM1YA-S01 Arm V (Vyxeos, venetoclax)Experimental Treatment6 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 VII: MM1YA-S01 Arm IV (Vyxeos)Experimental Treatment5 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 VIII: MM1YA-S01 Arm III (azacitidine, venetoclax)Experimental Treatment6 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 IX: MM1YA-S01 Arm II (cytarabine, daunorubicin, venetoclax)Experimental Treatment7 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 X: MM1YA-CTG01 Arm II (azacitidine, venetoclax)Experimental Treatment4 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 XI: MM1YA-CTG01 Arm I (daunorubicin, cytarabine, venetoclax)Experimental Treatment5 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 XII: MM1YA-A04 Regimen 2 (venetoclax, chemotherapy)Experimental Treatment9 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 XIII: MM1OA-S03 Arm 2 (ASTX727, venetoclax, enasidenib)Experimental Treatment6 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 XIV: MM1OA-EA02 Regimen 3 (azacitidine, venetoclax, gilteritinib)Experimental Treatment5 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 XV: MM1OA-EA02 Regimen 2 (azacitidine, venetoclax, gilteritinib)Experimental Treatment5 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 XVI: MM1OA-EA02 Regimen 1 (azacitidine, venetoclax)Experimental Treatment4 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 XVII: MM1MDS-A01 Arm B (ASTX727, enasidenib)Experimental Treatment4 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 XVIII: MM1MDS-A01 Arm A (ASTX727)Active Control3 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 XIX: MM1OA-S03 Arm 1 (ASTX727, venetoclax)Active Control5 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 XX: MM1YA-A04 Regimen 1 (gemtuzumab ozogamicin, chemotherapy)Active Control9 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 XXI: MM1YA-S01 Arm I (cytarabine, daunorubicin)Active Control6 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 XXII: MM2YA-EA01 Arm A (cytarabine)Active Control4 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 XXIII: MM1YA-CTG01 Arm III (daunorubicin, cytarabine)Active Control4 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.
Azacitidine is already approved in Canada, Japan for the following indications:
Approved in Canada as Vidaza for:
Myelodysplastic syndromes
Acute myeloid leukemia
Approved in Japan as Vidaza for:
Myelodysplastic syndromes
Acute myeloid leukemia
Find a Clinic Near You
Who Is Running the Clinical Trial?
National Cancer Institute (NCI)
Lead Sponsor
Trials
14,080
Recruited
41,180,000+
Dr. Douglas R. Lowy
National Cancer Institute (NCI)
Chief Executive Officer since 2023
MD from New York University School of Medicine
Dr. Monica Bertagnolli
National Cancer Institute (NCI)
Chief Medical Officer since 2022
MD from Harvard Medical School
Findings from Research
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.
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.
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.
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.
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]
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.
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.
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.
[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.
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.
Phase II, multicenter, randomized trial of CPX-351 (cytarabine:daunorubicin) liposome injection versus intensive salvage therapy in adults with first relapse AML. [2021]
Efficacy of CPX-351, (cytarabine:daunorubicin) liposome injection, against acute lymphoblastic leukemia (ALL) xenograft models of the Pediatric Preclinical Testing Program. [2021]
Leukemia-selective uptake and cytotoxicity of CPX-351, a synergistic fixed-ratio cytarabine:daunorubicin formulation, in bone marrow xenografts. [2022]
[Efficacy of venetoclax combined azacitidine in newly diagnosed acute myeloid leukemia unfit for standard chemotherapy: a single center experience]. [2023]