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New treatment option for MDS/MPN
Official title Active Myeloid Target Compound Combinations in MDS/MPN Overlap Syndromes Overlap Syndromes (ABNL-MARRO)
ClinicalTrials.gov ID: NCT04061421
What this study is testing
What is ASTX727?
ASTX727 is an investigational medicine, given as an once-daily pill taken by mouth, being studied as a potential treatment for mds/mpn.
Also referred to as Fixed dose combination of cedazuridine (100mg) + oral decitabine (35mg).
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- ABNL-MARRO (A Basket study of Novel therapy for untreated MDS/MPN and Relapsed/Refractory Overlap Syndromes) is an international European-American cooperation providing the framework for collaborative studies to advance treatment of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) and explore clinical-pathologic markers of disease severity, prognosis and treatment response. ABNL MARRO 001 (AM-001) is an Open label, phase 1/2 study within the framework of the ABNL-MARRO that will test novel treatment combinations in MDS/MPN.
- Phase 2: a mid-size study of how well it works
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- Must be ≥ 18 years of age at the time of signing the Informed Consent Form (ICF); must voluntarily sign an ICF; and must be willing and able to meet...
- Must have morphologically confirmed diagnosis of MDS/MPN, excluding JMML, in accordance with WHO (2016) diagnostic criteria (Appendix 1, Section...
- Treatment-naïve patients (patients who have had no prior disease-modifying therapy) may enroll in any AM-001 Arm that is open to accrual in phase 1...
- After an appropriate wash-out period, patients who have failed (or were intolerant to) prior therapy with a regimen(s) containing a DNMTi may enroll...
- Patients treated with DNMTi therapy prior to enrollment in AM-001 who failed to achieve a complete remission, per the MDS/MPN IWG response criteria...
You likely can't join if
- Patients should be excluded from any treatment Arm that includes a novel targeted agent to which they have had previous exposure. Novel targeted...
- Prior receipt of any investigational study drug, including treatment on any prior AM-001 Arm, within 30 days or 5 half-lives (whichever is shorter)...
- Prior receipt of any systemic antineoplastic therapy, including but not limited to prior DNMTi therapy, standard induction or cytotoxic chemotherapy...
- Known hypersensitivity to decitabine and ruxolitinib.
- Transformation to acute myeloid leukemia (e.g., \>20% myeloid blasts in bone marrow or \>20% circulating blasts in peripheral blood).
- Organ transplant recipients including allogeneic hematopoietic stem cell transplant.
See the full eligibility criteria
Who can join
- Must be ≥ 18 years of age at the time of signing the Informed Consent Form (ICF); must voluntarily sign an ICF; and must be willing and able to meet all study requirements.
- Must have morphologically confirmed diagnosis of MDS/MPN, excluding JMML, in accordance with WHO (2016) diagnostic criteria (Appendix 1, Section 12.1).
- Treatment-naïve patients (patients who have had no prior disease-modifying therapy) may enroll in any AM-001 Arm that is open to accrual in phase 1 or phase 2. Treatment-naïve patients may have received recombinant...
- After an appropriate wash-out period, patients who have failed (or were intolerant to) prior therapy with a regimen(s) containing a DNMTi may enroll in any Arm in phase 1b or any Arm which has met the criterion of the...
- Patients treated with DNMTi therapy prior to enrollment in AM-001 who failed to achieve a complete remission, per the MDS/MPN IWG response criteria, after at least 4 cycles of DNMTi therapy
- Patients enrolled in AM-001, or patients treated off-study with a regimen containing a DNMTi, who have definitive disease progression as defined in the protocol after at least 2 cycles of the prior therapy-this includes...
- Patients enrolled in AM-001 who have stable disease as best response at the second response evaluation after 6 cycles of the prior AM-001 therapy;
- Patients treated on AM-001 who had and recovered from an adverse event that precludes further therapy on that Arm; after recovery from a toxicity that is likely to be related to ASTX727, enrollment in another AM-001 may...
- Must be willing to undergo bone marrow biopsy with aspiration during screening and bone marrow aspiration with tissue collection for disease assessment and correlative studies periodically throughout the trial.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
- Life expectancy of at least 3 months, as assessed by the treating physician.
- For previously treated patients, recovery to ≤ Grade 1 or baseline of any toxicities due to prior systemic treatments, excluding alopecia.
- Must have adequate hepatic and renal function during screening as demonstrated by:
- ALT (SGPT) and AST (SGOT) ≤ 3x the institutional upper limit of normal (ULN);
- Total bilirubin ≤ 1.5x ULN or ≤ 2x ULN, if upon judgment of the treating investigator the elevated bilirubin is due to extramedullary hematopoiesis related to the underlying MDS/MPN or to Gilbert's disease;
- Calculated creatinine clearance (CrCl) ≥60 mL/min. For dose modification purposes in Arm B, CrCl should be calculated using the Cockcroft-Gault equation. For patients with renal impairment entering Arm B (ASTX727 +...
What rules you out
- Patients should be excluded from any treatment Arm that includes a novel targeted agent to which they have had previous exposure. Novel targeted agents in this study currently include itacitinib (INCB039110) and...
- Prior receipt of any investigational study drug, including treatment on any prior AM-001 Arm, within 30 days or 5 half-lives (whichever is shorter) before receiving the first dose of study drug in an Arm of AM-001...
- Prior receipt of any systemic antineoplastic therapy, including but not limited to prior DNMTi therapy, standard induction or cytotoxic chemotherapy (excluding hydroxyurea), or approved targeted agent within 21 days or...
- Known hypersensitivity to decitabine and ruxolitinib.
- Transformation to acute myeloid leukemia (e.g., \>20% myeloid blasts in bone marrow or \>20% circulating blasts in peripheral blood).
- Organ transplant recipients including allogeneic hematopoietic stem cell transplant.
- History of clinically significant or uncontrolled cardiac disease, including recent history (within 6 months) of unstable angina, acute myocardial infarction, New York Heart Association Class III or IV congestive heart...
- History of thromboemobolic events (such as deep vein thrombosis, pulmonary embolism, stroke, myocardial infraction) in the 6 months prior to study entry.
- Active HBV or HCV. Participants with positive total HBc antibody or positive HCV antibody must have negative viral load for HBV and HCV at screening.
- Known HIV seropositive status. For participants with unknown HIV status, HIV testing will be performed at screening.
- History of abnormal electrocardiogram (ECG) or presence of abnormal screening ECG that, in the investigator's opinion, is clinically significant and contraindicated for clinical study. Corrected QT interval (QTc), as...
- Any known contraindications to the use of ASTX727.
- Any sign of active and clinically significant bleeding.
- Other active malignancy, not including localized non-melanoma skin cancer, cervical carcinoma in situ, breast ductal carcinoma in situ of the breast, or localized prostate cancer controlled with hormone therapy...
- Receipt of wide-field radiotherapy (including therapeutic radioisotopes) ≤ 28 days or limited field radiation for palliation ≤ 14 days prior to starting study medications; or has not recovered from side effects of such...
- Patients who require continuation of a prohibited concomitant medication (Section 6.6) for which no alternative therapy or allowable substitute is available.
- Active, uncontrolled infection. Patients with infection that is under control with active treatment are eligible.
- Major surgery requiring general anesthesia within 4 weeks prior to starting study treatment. (Placement of a central line or port-a-catheter is acceptable within this time frame and does not exclude the patient.)
- Women who are pregnant or lactating.
- people who expect to conceive or father children within the projected duration of the study and/or who are unwilling to use highly effective methods of contraception throughout the duration of the study, starting with...
- Any concurrent serious or unstable medical or psychiatric condition that in the investigator's opinion would jeopardize the patient's ability to provide informed consent or to comply with the protocol.
- Any psychological, familial, geographical or sociological condition that in the investigator's opinion would jeopardize the patient's ability to comply with the protocol.
The study team makes the final eligibility decision.
Where it's taking place
- Tampa, Florida, United States
- Rochester, New York, United States
- Portland, Oregon, United States
- Nashville, Tennessee, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Tampa, Florida, United States; Rochester, New York, United States; Portland, Oregon, United States; Nashville, Tennessee, United States. Enter your location above to see the nearest site and check your eligibility.
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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.