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Safety, Tolerability, Pharmacokinetics, and Efficacy of AZD2811 Nanoparticles as Monotherapy or in Combination in Acute Myeloid Leukemia Participants.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03217838
Recruitment Status : Terminated (strategic decision)
First Posted : July 14, 2017
Last Update Posted : April 5, 2022
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
This is a Phase I/II clinical study to determine the maximum tolerated dose (MTD), and schedule, safety, tolerability, pharmacokinetics, and pharmacodynamics of AZD2811 monotherapy or with combination agent(s) in relapsed/refractory acute myeloid leukaemia (AML) participants or treatment-naïve AML participants not eligible for intensive induction therapy. In addition, the study will explore the potential clinical activity by assessing anti-tumour activity in participants. The study was terminated early as a result of AstraZeneca's strategic review across the AZD2811 programme. Part A data were collected for initial cohorts; the MTD/recommended Phase 2 dose (RP2D) dose and schedule of AZD2811 monotherapy or with combination agents were not determined. Part B of the study was not initiated

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukaemia Drug: AZD2811 Drug: Azacitidine Drug: Venetoclax Phase 1

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Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 50 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II, Open-Label, Multicentre 2-Part Study to Assess the Safety, Tolerability, Pharmacokinetics, and Efficacy of AZD2811 as Monotherapy or in Combination in Treatment-Naïve or Relapsed/Refractory Acute Myeloid Leukaemia Patients Not Eligible for Intensive Induction Therapy.
Actual Study Start Date : July 31, 2017
Actual Primary Completion Date : March 25, 2021
Actual Study Completion Date : March 25, 2021


Arm Intervention/treatment
Experimental: Group 1 Arm A (AZD2811 Dose 1)
Participants with AML will receive intevenous (IV) infusion of AZD2811 Dose 1 on Days 1 and 4 of each 28-day cycle until disease progression, unacceptable toxicity, or the decision to discontinue treatment by the participant or the study physician, whichever occurs first.
Drug: AZD2811
AZD2811 will be administered by IV infusion with the specified dose level as reported in arms in 28-day cycles.
Other Names:
  • AZD1152 hQPA
  • AZD1152 hydroxyl-quinazoline pyrazole anilide

Experimental: Group 1 Arm A (AZD2811 Dose 2)
Participants with AML and myelodysplastic syndrome (MDS) will receive IV infusion of AZD2811 Dose 2 on Days 1 and 4 of each 28-day cycle until disease progression, unacceptable toxicity, or the decision to discontinue treatment by the participant or the study physician, whichever occurs first.
Drug: AZD2811
AZD2811 will be administered by IV infusion with the specified dose level as reported in arms in 28-day cycles.
Other Names:
  • AZD1152 hQPA
  • AZD1152 hydroxyl-quinazoline pyrazole anilide

Experimental: Group 1 Arm A (AZD2811 Dose 3)
Participants with AML and MDS will receive IV infusion of AZD2811 Dose 3 on Days 1 and 4 of each 28-day cycle until disease progression, unacceptable toxicity, or the decision to discontinue treatment by the participant or the study physician, whichever occurs first.
Drug: AZD2811
AZD2811 will be administered by IV infusion with the specified dose level as reported in arms in 28-day cycles.
Other Names:
  • AZD1152 hQPA
  • AZD1152 hydroxyl-quinazoline pyrazole anilide

Experimental: Group 1 Arm A (AZD2811 Dose 4)
Participants with AML and MDS will receive IV infusion of AZD2811 Dose 4 on Days 1 and 4 of each 28-day cycle until disease progression, unacceptable toxicity, or the decision to discontinue treatment by the participant or the study physician, whichever occurs first.
Drug: AZD2811
AZD2811 will be administered by IV infusion with the specified dose level as reported in arms in 28-day cycles.
Other Names:
  • AZD1152 hQPA
  • AZD1152 hydroxyl-quinazoline pyrazole anilide

Experimental: Group 1 Arm A (AZD2811 Dose 5)
Participants with AML will receive IV infusion of AZD2811 Dose 5 on Days 1 and 4 of each 28-day cycle until disease progression, unacceptable toxicity, or the decision to discontinue treatment by the participant or the study physician, whichever occurs first.
Drug: AZD2811
AZD2811 will be administered by IV infusion with the specified dose level as reported in arms in 28-day cycles.
Other Names:
  • AZD1152 hQPA
  • AZD1152 hydroxyl-quinazoline pyrazole anilide

Experimental: Group 1 Arm B (AZD2811 Dose 2)
Participants with AML will receive IV infusion of AZD2811 Dose 2 on Days 1, 4, 15, and 18 of each 28-day cycle until disease progression, unacceptable toxicity, or the decision to discontinue treatment by the participant or the study physician, whichever occurs first.
Drug: AZD2811
AZD2811 will be administered by IV infusion with the specified dose level as reported in arms in 28-day cycles.
Other Names:
  • AZD1152 hQPA
  • AZD1152 hydroxyl-quinazoline pyrazole anilide

Experimental: Group 1 Arm B (AZD2811 Dose 6)
Participants with AML will receive IV infusion of AZD2811 Dose 6 on Days 1, 4, 15, and 18 of each 28-day cycle until disease progression, unacceptable toxicity, or the decision to discontinue treatment by the participant or the study physician, whichever occurs first.
Drug: AZD2811
AZD2811 will be administered by IV infusion with the specified dose level as reported in arms in 28-day cycles.
Other Names:
  • AZD1152 hQPA
  • AZD1152 hydroxyl-quinazoline pyrazole anilide

Experimental: Group 2 Arm A (AZD2811 Dose 3 + Azacitidine 75 mg/m^2)
Participants with AML and MDS will receive Azacitidine 75 mg/m^2 of body surface area (BSA) by subcutaneous (SC) injection or IV infusion prior to the start of AZD2811 infusion on Days 1 through 7 or for 5 consecutive weekdays (Days 1 through 5) with treatment holidays on the 2 weekend days (Days 6 and 7), and the remaining azacitidine dosing will be administered on the first 2 weekdays of the 2nd week (Days 8 and 9) of each 28-day cycle. Participants will receive IV infusion of AZD2811 Dose 3 on Days 1 and 4 of each 28-day cycle. Participants will receive the study treatment until disease progression, unacceptable toxicity, or the decision to discontinue treatment by the participant or the study physician, whichever occurs first.
Drug: AZD2811
AZD2811 will be administered by IV infusion with the specified dose level as reported in arms in 28-day cycles.
Other Names:
  • AZD1152 hQPA
  • AZD1152 hydroxyl-quinazoline pyrazole anilide

Drug: Azacitidine
Azacitidine is supplied in vials of 25 mg/mL powder for suspension for injection. After reconstitution, each vial contains a maximum of 100 mg. Participants should be pre-medicated for nausea and vomiting according to institutional standards before receiving azacitidine. Participants will receive 75 mg/m² on Days 1 through 7 or for 5 consecutive weekdays with rest on the 2 weekend days, and azacitidine dosing the first 2 weekdays of the next week of each 28-day cycle.
Other Name: Vidaza (TM)

Experimental: Group 2 Arm A (AZD2811 Dose 4 + Azacitidine 75 mg/m^2)
Participants with AML will receive Azacitidine 75 mg/m^2 of BSA by SC injection or IV infusion prior to the start of AZD2811 infusion on Days 1 through 7 or for 5 consecutive weekdays (Days 1 through 5) with treatment holidays on the 2 weekend days (Days 6 and 7), and the remaining azacitidine dosing will be administered on the first 2 weekdays of the 2nd week (Days 8 and 9) of each 28-day cycle. Participants will receive IV infusion of AZD2811 Dose 4 on Days 1 and 4 of each 28-day cycle. Participants will receive the treatment until disease progression, unacceptable toxicity, or the decision to discontinue treatment by the participant or the study physician, whichever occurs first.
Drug: AZD2811
AZD2811 will be administered by IV infusion with the specified dose level as reported in arms in 28-day cycles.
Other Names:
  • AZD1152 hQPA
  • AZD1152 hydroxyl-quinazoline pyrazole anilide

Drug: Azacitidine
Azacitidine is supplied in vials of 25 mg/mL powder for suspension for injection. After reconstitution, each vial contains a maximum of 100 mg. Participants should be pre-medicated for nausea and vomiting according to institutional standards before receiving azacitidine. Participants will receive 75 mg/m² on Days 1 through 7 or for 5 consecutive weekdays with rest on the 2 weekend days, and azacitidine dosing the first 2 weekdays of the next week of each 28-day cycle.
Other Name: Vidaza (TM)

Experimental: Group 2 Arm B (AZD2811 Dose 2 + Azacitidine 75 mg/m^2)
Participants with AML will receive Azacitidine 75 mg/m^2 of BSA by SC injection or IV infusion prior to the start of AZD2811 infusion on Days 1 through 7 or for 5 consecutive weekdays (Days 1 through 5) with treatment holidays on the 2 weekend days (Days 6 and 7), and the remaining azacitidine dosing will be administered on the first 2 weekdays of the 2nd week (Days 8 and 9) of each 28-day cycle. Participants will receive IV infusion of AZD2811 Dose 2 on Days 1, 4, 15, and 18 of each 28-day cycle. Participants will receive the treatment until disease progression, unacceptable toxicity, or the decision to discontinue treatment by the participant or the study physician, whichever occurs first.
Drug: AZD2811
AZD2811 will be administered by IV infusion with the specified dose level as reported in arms in 28-day cycles.
Other Names:
  • AZD1152 hQPA
  • AZD1152 hydroxyl-quinazoline pyrazole anilide

Drug: Azacitidine
Azacitidine is supplied in vials of 25 mg/mL powder for suspension for injection. After reconstitution, each vial contains a maximum of 100 mg. Participants should be pre-medicated for nausea and vomiting according to institutional standards before receiving azacitidine. Participants will receive 75 mg/m² on Days 1 through 7 or for 5 consecutive weekdays with rest on the 2 weekend days, and azacitidine dosing the first 2 weekdays of the next week of each 28-day cycle.
Other Name: Vidaza (TM)

Experimental: Group 2 Arm B (AZD2811 Dose 6 + Azacitidine 75 mg/m^2)
Participants with AML will receive Azacitidine 75 mg/m^2 of BSA by SC injection or IV infusion prior to the start of AZD2811 infusion on Days 1 through 7 or for 5 consecutive weekdays (Days 1 through 5) with treatment holidays on the 2 weekend days (Days 6 and 7), and the remaining azacitidine dosing will be administered on the first 2 weekdays of the 2nd week (Days 8 and 9) of each 28-day cycle. Participants will receive IV infusion of AZD2811 Dose 6 on Days 1, 4, 15, and 18 of each 28-day cycle. Participants will receive the treatment until disease progression, unacceptable toxicity, or the decision to discontinue treatment by the participant or the study physician, whichever occurs first.
Drug: AZD2811
AZD2811 will be administered by IV infusion with the specified dose level as reported in arms in 28-day cycles.
Other Names:
  • AZD1152 hQPA
  • AZD1152 hydroxyl-quinazoline pyrazole anilide

Drug: Azacitidine
Azacitidine is supplied in vials of 25 mg/mL powder for suspension for injection. After reconstitution, each vial contains a maximum of 100 mg. Participants should be pre-medicated for nausea and vomiting according to institutional standards before receiving azacitidine. Participants will receive 75 mg/m² on Days 1 through 7 or for 5 consecutive weekdays with rest on the 2 weekend days, and azacitidine dosing the first 2 weekdays of the next week of each 28-day cycle.
Other Name: Vidaza (TM)

Experimental: Group 3 Arm A (AZD2811 Dose 2 + Venetoclax 200 mg)
Participants with AML will receive IV infusion of AZD2811 Dose 2 on Days 1 and 4 of each 28-day cycle and venetoclax 100 mg orally (PO) on Day 1 and 200 mg PO from Days 2 to 28 of each 28-day cycle until disease progression, unacceptable toxicity, or the decision to discontinue treatment by the participant or the study physician, whichever occurs first.
Drug: AZD2811
AZD2811 will be administered by IV infusion with the specified dose level as reported in arms in 28-day cycles.
Other Names:
  • AZD1152 hQPA
  • AZD1152 hydroxyl-quinazoline pyrazole anilide

Drug: Venetoclax
Venetoclax (VENCLEXTA®) is approved by the FDA for use in combination with azacitidine, or decitabine, or low-dose cytarabine for the treatment of newly-diagnosed AML in adults who are age 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy. Venetoclax is planned to be given at a dose of 100 mg orally (PO) on Day 1 and 200 mg (PO) on Days 2- 28 of each 28-day cycle or 100 mg orally (PO) on Day 1, 200 mg PO on Day 2, and 400 mg PO from Days 3 to 28 of each 28-day cycle. The third participant in Group 3 Arm A will only be enrolled after the first 2 participants will receive ≥2 weeks of treatment and have shown no evidence of toxicity observed to be compatible with a DLT.
Other Name: Venclexta (TM)

Experimental: Group 3 Arm A (AZD2811 Dose 2 + Venetoclax 400 mg)
Participants with AML will receive IV infusion of AZD2811 Dose 2 on Days 1 and 4 of each 28-day cycle and venetoclax 100 mg orally (PO) on Day 1, 200 mg PO on Day 2, and 400 mg PO from Days 3 to 28 of each 28-day cycle until disease progression, unacceptable toxicity, or the decision to discontinue treatment by the participant or the study physician, whichever occurs first.
Drug: AZD2811
AZD2811 will be administered by IV infusion with the specified dose level as reported in arms in 28-day cycles.
Other Names:
  • AZD1152 hQPA
  • AZD1152 hydroxyl-quinazoline pyrazole anilide

Drug: Venetoclax
Venetoclax (VENCLEXTA®) is approved by the FDA for use in combination with azacitidine, or decitabine, or low-dose cytarabine for the treatment of newly-diagnosed AML in adults who are age 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy. Venetoclax is planned to be given at a dose of 100 mg orally (PO) on Day 1 and 200 mg (PO) on Days 2- 28 of each 28-day cycle or 100 mg orally (PO) on Day 1, 200 mg PO on Day 2, and 400 mg PO from Days 3 to 28 of each 28-day cycle. The third participant in Group 3 Arm A will only be enrolled after the first 2 participants will receive ≥2 weeks of treatment and have shown no evidence of toxicity observed to be compatible with a DLT.
Other Name: Venclexta (TM)




Primary Outcome Measures :
  1. Number of Participants With Dose-limiting Toxicities (DLTs) [ Time Frame: Day 1 to Day 28 of first cycle ]
    A DLT was defined as any adverse event (AE) not related to the underlying leukaemia requiring treatment interruption for > 21 days, any Grade 5 AE, Grade 4 neutropenia or thrombocytopenia lasting >= 42 days from start of cycle in absence of evidence of active leukaemia, any >= Grade 3 non-haematological AE (except Grade 3 nausea, vomiting, mucositis, stomatitis or diarrhoea that was controlled within 4 days and Grade 3 elevations in alanine aminotransferase/ aspartate aminotransferase that return to meet initial eligibility criteria within 7 days of study drug interruption), or any other clinically significant and/or unacceptable AE that does not respond to supportive care, results in a disruption of dosing schedule for > 7 days, or was judged as a DLT by Investigator in collaboration with the Medical Monitor. An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.

  2. Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) [ Time Frame: Day 1 through early termination of the study (approximately 42 months) ]
    An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. There will be no updated results for this outcome measures at the time of end of study.

  3. Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Grade 4 TEAEs [ Time Frame: Day 1 through early termination of the study (approximately 42 months) ]

    Participants with abnormal clinical laboratory parameters reported as Grade 4 TEAEs are reported. Laboratory analysis included hematology, clinical chemistry, and urinalysis.

    hematology, coagulation, chemistry, and urinalysis parameters over time are reported.



Secondary Outcome Measures :
  1. Number of Participants With Total Complete Remission (CR) [ Time Frame: Day 1 through early termination of the study (approximately 42 months) ]
    Total complete remission included CR and CR with incomplete recovery (CRi). The CR is defined as bone marrow blasts <5%, absence of blasts with Auer rods, absence of extramedullary disease, absolute neutrophil count >1.0 × 10/L, platelet count >100 × 10/L, and independence of red cell transfusions. The CRi includes all CR criteria except for residual neutropenia (<1.0 × 10/L) or thrombocytopenia (<100 × 10/L).

  2. Number of Participants With Overall Response Rate (ORR) [ Time Frame: Day 1 through early termination of the study (approximately 42 months) ]
    The ORR included CR, CRi, and partial remission (PR). The CR is defined as bone marrow blasts <5%, absence of blasts with Auer rods, absence of extramedullary disease, absolute neutrophil count >1.0 × 10/L, platelet count >100 × 10/L, and independence of red cell transfusions. The CRi includes all CR criteria except for residual neutropenia (<1.0 × 10/L) or thrombocytopenia (<100 × 10/L). The PR is defined as all hematologic criteria of CR (absolute neutrophil count >1.0 × 10/L, platelet count >100 × 10/L, and independence of red cell transfusions), decrease of bone marrow blast percentage to 5% to 25%, and decrease of pre-treatment bone marrow blast percentage by at least 50%.

  3. Number of Participants With Partial Remission (PR) [ Time Frame: Day 1 through early termination of the study (approximately 42 months) ]
    The PR is defined as all hematologic criteria of CR (absolute neutrophil count >1.0 × 10/L, platelet count >100 × 10/L, and independence of red cell transfusions), decrease of bone marrow blast percentage to 5% to 25%, and decrease of pre-treatment bone marrow blast percentage by at least 50%.

  4. Number of Participants With >50% Change in Bone Marrow Blasts from Baseline in Participants With AML [ Time Frame: Baseline (Day 1), Cycle 1 Day 22, Cycle 2 Day 22, Cycle 4 Day 22, and end of treatment (approximately 42 months) ]
    Participants with >50% change in myleloblasts from baseline are reported.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria

  1. AML participants who have either: (a) relapsed or are refractory to standard therapies (the participant may have been treated with standard therapy prior to the diagnosis of AML e.g. for MDS), OR (b) diagnosis of AML (bone marrow blasts ≥ 20%), who are previously untreated for AML, and are not suitable for intensive induction therapy, as defined below (for AZD2811 monotherapy and HMA combination participants only i.e. inclusion criteria 1(b) may only be used to enrol a participant into Groups 1 and 2; previously untreated AML participants may not enrol into Group 3 unless they fulfil inclusion criteria 1(a) above).

    Participants are unsuitable for intensive induction therapy if they are:

    • 75 years or

      • 75 years of age with clinically significant cardiac or pulmonary dysfunction unrelated to leukaemia, as reflected by at least 1 of the following criteria: Left ventricular ejection fraction (LVEF) ≤50% Diffusing capacity of the lungs for carbon monoxide (DLCO) ≤65% of expected Forced expiratory volume 1(FEV1) ≤65% of expected Chronic stable angina any significant co-morbidities which in the opinion of the treating physician makes the participant unsuitable for intensive induction therapy. This must be documented by the study monitor.
  2. AML participants who are unlikely to demonstrate rapid progression such that they would be unable to complete the first cycle of therapy.
  3. Provision of signed and dated, written informed consent prior to any study-specific procedures, sampling and analyses.
  4. Aged at least 18 years
  5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2.
  6. Prior treatment with hydroxyurea (up to 24 hours before study treatment) is allowed
  7. Adequate organ system function as outlined below:

    Prothrombin time (PT)/partial thromboplastin time (PTT) ≤1.5 x upper limit of normal (ULN) Total bilirubin ≤1.5 x ULN. Participants with documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) who have serum bilirubin ≤3 x the ULN may be enrolled, unless there is evidence of hemolytic anemia Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ˂2.5 x ULN if no liver involvement or ≤5 times the ULN with liver involvement Creatinine ≤1.5 x ULN, OR calculated or measured creatinine clearance ≥50 mL/min as calculated by the Cockcroft-Gault method, OR 24-hour measured urine creatinine clearance ≥50 mL/min.

    Participants enrolled in the venetoclax combination part with a creatinine clearance (CLcr) <80 mL/min (and ≥ 45 mL/min) as calculated by Cockcroft-Gault should be able to have more intensive prophylaxis and monitoring (according to institutional standard) to reduce the risk of tumour lysis syndrome (TLS) when initiating treatment with venetoclax.

  8. Females should be using adequate contraception, should not be breast feeding and must have a negative serum pregnancy test prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening: a) Post-menopausal defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments, b) have documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.

9 Sexually active male participants should be willing to use barrier contraception i.e., condoms. Female partners of male participants should also use a highly effective form of contraception if they are of childbearing potential, unless the male participant is abstaining from sexual intercourse.

Exclusion criteria

  1. Treatment with any of the following:

    Any investigational agents, experimental antibody or antibody drug conjugates, or study drugs from a previous clinical study within 3-4 weeks of said prior investigational agent(s) with regard to the first dose of study treatment on this clinical study protocol.

    Any other chemotherapy (except hydroxyurea), immunotherapy or anticancer agents within 2 weeks of the first dose of study treatment

    Any haematopoietic growth factors (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF]) within 7 days of the first dose of AZD2811 monotherapy or with combination agent(s) or pegylated G-CSF (pegfilgrastim) or darbepoetin within 14 days of the first dose of study treatment

    Prescription or non-prescription drugs or other products known to be strong inhibitors/inducers of CYP3A that cannot be discontinued prior to Day 1 of dosing and withheld throughout the study until 2 weeks after the last dose of study drug. Washout periods should be a minimum of 5 half-lives depending on the medication.

    Participants who have undergone allogeneic stem cell transplant within 12 months are excluded. If allogeneic transplant was >12 months ago, then they are not excluded as long as they are off all immunosuppression and have no signs or symptoms of active graft versus host disease.

    Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study treatment

  2. With the exception of alopecia, any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of starting study treatment .
  3. Presence of, or history of leptomeningeal disease.
  4. As judged by the Investigator, any evidence of: severe or uncontrolled systemic diseases (e.g., severe hepatic impairment, interstitial lung disease [bilateral, diffuse, parenchymal lung disease]) or other malignancy (like advanced malignant hepatic tumours); current unstable or uncompensated respiratory or cardiac conditions; or uncontrolled hypertension; history of, or active, bleeding diatheses (e.g., haemophilia or von Willebrand disease); participants with inflammatory bowel disease (e.g., Crohn or colitis ulcerosa); uncontrolled active systemic fungal, bacterial, viral, or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment); or IV anti-infective treatment within 2 weeks before first dose of study treatment unless either clear evidence would indicate that despite the clinical symptoms no infection took place, or just a single dose of IV antibiotics was administered followed by oral treatment thereafter.
  5. Any of the following cardiac criteria: a) Congestive heart failure (CHF) per New York Heart Association (NYHA) classification > Class II, b) Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy, c) Unstable angina or new-onset angina, d) QTcF interval >450 ms (for male participants) or >470 ms (for female participants) on screening electrocardiogram (ECG).
  6. Active non-infectious skin disease (including rash, dermatitis, or psoriasis, but excluding stable plaque psoriasis from the definition of active disease). Participants with a rash that is biopsy-proven leukaemia or with pressure ulcers are not excluded. Participants with petechiae from thrombocytopenia or participants with drug related rashes that are improving are not excluded..
  7. Participants with a known hypersensitivity to azacitidine or mannitol (HMA combination participants only).
  8. History of hypersensitivity to active or inactive excipients (e.g., PEG) of any drug in the study or drugs with a similar chemical structure or class to those investigated in the study.
  9. Known history of infection with human immunodeficiency virus (HIV)
  10. Serologic status reflecting active hepatitis B or C infection:

    1. Participants who are anti-HBc positive and who are surface antigen negative will need to have a negative polymerase chain reaction (PCR) result before enrolment. Those who are hepatitis B surface antigen positive or hepatitis B PCR positive will be excluded.
    2. Participants who are hepatitis C antibody positive will need to have a negative PCR result before enrolment. Those who are hepatitis C PCR positive will be excluded.

Additional exclusion criteria - venetoclax combination

  1. Adults with previously untreated diagnosis of AML (bone marrow blasts ≥ 20%), unless they fulfil inclusion criterion 1(a) above.
  2. White blood cell (WBC) count > 25,000 cells/mm^3 (25 x 10^9/L); use of leukapheresis or hydroxyurea before venetoclax initiation is allowed to achieve this entry criterion (leukapheresis or hydroxyurea must be stopped at least 48 hours before the initiation of venetoclax).
  3. AML with known active central nervous system involvement.
  4. Chronic respiratory disease that requires continuous oxygen use.
  5. Previous venetoclax exposure that ended due to venetoclax toxicity.
  6. Use of moderate CYP3A inhibitor/inducers and P-gP inhibitors, with the exception of fluconazole and isavuconazole, that cannot be discontinued prior to Day 1 of dosing. Washout periods should be a minimum of 5 half-lives depending on the medication unless agreed upon with the Sponsor.
  7. Participant consumed grapefruit, grapefruit products, Seville oranges (including marmalades containing Seville oranges) or star fruit within 3 days before the initiation of venetoclax.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03217838


Locations
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United States, Colorado
Research Site
Denver, Colorado, United States, 80218
United States, Florida
Research Site
Sarasota, Florida, United States, 34232
United States, Michigan
Research Site
Detroit, Michigan, United States, 48201
United States, North Carolina
Research Site
Charlotte, North Carolina, United States, 28204
United States, Ohio
Research Site
Canton, Ohio, United States, 44718
United States, Oklahoma
Research Site
Oklahoma City, Oklahoma, United States, 73104
United States, Tennessee
Research Site
Nashville, Tennessee, United States, 37203
United States, Texas
Research Site
Dallas, Texas, United States, 75246
Research Site
Houston, Texas, United States, 77030
United States, Wisconsin
Research Site
Milwaukee, Wisconsin, United States, 53226
Australia
Research Site
Melbourne, Australia, 3004
Sponsors and Collaborators
AstraZeneca
Investigators
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Principal Investigator: Howard Burris, MD SCRI Development Innovations, LLC
Additional Information:
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03217838    
Other Study ID Numbers: D6130C00003
HEMREF 41 ( Other Identifier: Sarah Cannon Development Innovations, LLC )
First Posted: July 14, 2017    Key Record Dates
Last Update Posted: April 5, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
AML
Acute Myeloid Leukaemia
AZD2811
AZD1152
AZD1152 hQPA
barasertib
azacitidine
VIDAZA®
venetoclax
VENCLEXTA®
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Azacitidine
Venetoclax
Pyrazole
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors