Study of ASTX727 vs IV Decitabine in MDS CMML and AML

  • STATUS
    Recruiting
  • End date
    May 31, 2022
  • participants needed
    200
  • sponsor
    Astex Pharmaceuticals, Inc.
Updated on 27 January 2021
anemia
chronic myelomonocytic leukemia
secondary aml
decitabine
direct bilirubin
leukemia
induction chemotherapy
secondary acute myeloid leukemia
blast cells
conjugated bilirubin
myelomonocytic leukemia
ringed sideroblasts
astx727
secondary myelodysplastic syndrome

Summary

Multicenter, randomized, open-label, crossover PK study of ASTX727 versus IV decitabine. Adult subjects who are candidates to receive IV decitabine will be randomized 1:1 to receive the ASTX727 tablet Daily5 in Cycle 1 followed by IV decitabine 20 mg/m^2 Daily5 in Cycle 2, or the converse order. After completion of PK studies during the first 2 treatment cycles, subjects will continue to receive treatment with ASTX727 from Cycle 3 onward (in 28-day cycles) until disease progression, unacceptable toxicity, or the subject discontinues treatment or withdraws from the study.

Description

This Phase 3 study will establish PK equivalence of ASTX727 to IV decitabine in approximately 118 evaluable subjects. Eligible subjects will receive both study treatments: oral investigational drug ASTX727, and IV decitabine, as follows: subjects will be randomly assigned 1:1 to receive ASTX727 or IV decitabine in Cycle 1 and then cross over to the other therapy in Cycle 2.

In the ASTX727 cycle, subjects will receive the ASTX727 tablet Daily5. Serial PK measurements (blood draws) will be done on Days 1, 2, and 5, along with pre-dose PK assessments on Days 1-5 and an assessment at 3 hours post dose on Day 3. Subjects will be required to fast from food for 4 hours on days when receiving ASTX727: at least 2 hours before and 2 hours after dosing.

In the IV decitabine cycle, subjects will receive a 1-hour infusion of IV decitabine 20 mg/m^2 Daily5. Serial PK measurements will be done on Days 1 and 5, along with pre-dose and 1-hour post-infusion assessments on Day 3.

In Cycles 3, subjects will receive the ASTX727 tablet Daily5 in 28-day cycles. (No PK assessments will be done from Cycle 3 onward.)

Details
Condition Bone marrow disorder, Chronic myelomonocytic leukemia, Juvenile Myelomonocytic Leukemia, Preleukemia, Acute myeloid leukemia, MYELODYSPLASTIC SYNDROME, Myelodysplastic Syndromes (MDS), Acute Myelogenous Leukemia (AML), myelodysplastic syndromes, myelodysplastic syndrome (mds), acute myelogenous leukemia, anll, acute myeloblastic leukemia, chronic myelomonocytic leukaemia, cmml
Treatment ASTX727, Dacogen
Clinical Study IdentifierNCT03306264
SponsorAstex Pharmaceuticals, Inc.
Last Modified on27 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Able to understand and comply with the study procedures, understand the risks involved in the study, and provide written informed consent before the first study-specific procedure; specifically able to comply with the PK assessment schedule during the first 2 treatment cycles
Men or women 18 years who are candidates to receive IV decitabine according to FDA or European Medicines Agency (EMA) approved indications
In North America: Participants with MDS previously treated or untreated with de novo or secondary MDS, including all French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia [CMML]), and subjects with MDS International Prognostic Scoring System (IPSS) int-1, -2, or high-risk MDS
In Europe: Participants with de novo or secondary AML, as defined by the World Health Organization (WHO) criteria, who are not candidates for standard induction chemotherapy
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
Adequate organ function defined as follows
Hepatic: Total or direct bilirubin 2 upper limit of normal (ULN); aspartate transaminase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine transaminase/serum glutamic pyruvic transaminase (ALT/SGPT) 2.5 ULN
Renal: serum creatinine 1.5 ULN or calculated creatinine clearance or glomerular filtration rate >50 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal
No major surgery within 30 days of first study treatment
Life expectancy of at least 3 months
Women of child-bearing potential must not be pregnant or breastfeeding and must have a negative pregnancy test at screening. Women of non-childbearing potential are those who have had a hysterectomy or bilateral oophorectomy, or who have completed menopause, defined as no menses for at least 1 year AND either age 65 years or follicle-stimulating hormone levels in the menopausal range
Subjects and their partners with reproductive potential must agree to use effective contraceptive measures during the study and for 3 months after the last dose of study treatment. Effective contraception includes methods such as oral contraceptives or double-barrier method (eg, use of a condom AND diaphragm, with spermicide)

Exclusion Criteria

Prior treatment with more than 1 cycle of azacitidine or decitabine. Prior cytotoxic chemotherapy for AML except for hydroxyurea to control high white blood cell (WBC) counts
Hospitalization for more than 2 days for documented febrile neutropenia, pneumonia, sepsis, or systemic infection in the 30 days before screening
Treatment with any investigational drug or therapy within 2 weeks of study treatment, or 5 half-lives, whichever is longer, before the first dose of study treatment, or ongoing clinically significant adverse events (AEs) from previous treatment
Cytotoxic chemotherapy or prior azacitidine or decitabine within 4 weeks of first dose of study treatment
Concurrent MDS therapies, including lenalidomide, erythropoietin, cyclosporine/tacrolimus, granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor, etc. (Prior treatment with these agents is permitted, provided that completion is at least 1 week before the first dose of study treatment.)
Poor medical risk because of other conditions such as uncontrolled systemic diseases, active uncontrolled infections, or comorbidities that may put the patient at risk of not being able to complete at least 2 cycles of treatment
Known significant mental illness or other condition, such as active alcohol or other substance abuse or addiction, that in the opinion of the investigator predisposes the subject to high risk of noncompliance with the protocol
Rapidly progressive or highly proliferative disease (total white blood cell count of >15 10^9/L) or other criteria that render the subject at high risk of requiring intensive cytotoxic chemotherapy within the next 3 months
Life-threatening illness or severe organ system dysfunction, such as uncontrolled congestive heart failure or chronic obstructive pulmonary disease, or other reasons including laboratory abnormalities, which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of ASTX727, or compromise completion of the study or integrity of the study outcomes
Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, prostate cancer or breast cancer under control with hormone therapy, or other cancer from which the subject has been disease free for at least 2 years
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