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History of Changes for Study: NCT02421939
A Study of ASP2215 Versus Salvage Chemotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With FMS-like Tyrosine Kinase (FLT3) Mutation
Latest version (submitted September 9, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 April 16, 2015 None (earliest Version on record)
2 June 12, 2015 Study Status
3 July 27, 2015 Study Status, Eligibility and Study Description
4 September 25, 2015 Study Status, Eligibility and Study Description
5 October 8, 2015 Recruitment Status, Study Status and Contacts/Locations
6 November 18, 2015 Study Status and Contacts/Locations
7 February 3, 2016 Study Status, IPDSharing and Contacts/Locations
8 February 5, 2016 Eligibility and Study Status
9 March 11, 2016 Study Status and Contacts/Locations
10 February 14, 2017 Contacts/Locations, Study Status, Eligibility and Oversight
11 March 28, 2017 Study Status and Oversight
12 April 26, 2017 Study Status and Contacts/Locations
13 May 31, 2017 Study Status and Contacts/Locations
14 July 25, 2017 Contacts/Locations, Study Status and Oversight
15 August 23, 2017 Study Status and Contacts/Locations
16 October 31, 2017 Outcome Measures, Contacts/Locations, Arms and Interventions, Study Status, Study Description, Eligibility and Conditions
17 February 2, 2018 Study Status and Contacts/Locations
18 March 16, 2018 Recruitment Status, Contacts/Locations, Study Status and Study Design
19 March 19, 2018 Contacts/Locations and Study Status
20 April 23, 2018 Study Status
21 June 13, 2018 Study Status and Contacts/Locations
22 September 25, 2018 Study Status and Contacts/Locations
23 October 31, 2018 Study Status
24 November 6, 2018 Study Status
25 November 13, 2018 Study Status
26 January 4, 2019 Study Status, Contacts/Locations, Arms and Interventions and Conditions
27 January 14, 2019 Contacts/Locations and Study Status
28 January 31, 2019 Contacts/Locations and Study Status
29 February 20, 2019 Study Status and Contacts/Locations
30 March 12, 2019 Study Status and Contacts/Locations
31 May 22, 2019 Study Status
32 July 23, 2019 Study Status
Show
Results Submission Events
33 October 16, 2019 Outcome Measures, IPDSharing, Study Status, Arms and Interventions, Study Description, Oversight, Document Section, Results and Eligibility
34 March 5, 2020 Study Status
35 April 3, 2020 Study Status
36 June 5, 2020 Study Status
37 July 14, 2020 Study Status
38 August 20, 2020 Study Status
39 September 11, 2020 Study Status
40 October 15, 2020 Study Status
41 November 20, 2020 Study Status
42 December 2, 2020 Study Status
43 December 22, 2020 Study Status
44 January 14, 2021 Study Status
45 February 17, 2021 Study Status
46 March 19, 2021 Study Status
47 April 19, 2021 Study Status
48 May 14, 2021 Study Status
49 June 9, 2021 Study Status
50 July 8, 2021 Study Status
51 August 13, 2021 Study Status
52 September 21, 2021 Study Status
53 September 29, 2021 Contacts/Locations and Study Status
54 October 11, 2021 Study Status
55 November 11, 2021 Study Status
56 November 29, 2021 Study Status
57 January 26, 2022 Study Status
58 February 14, 2022 Study Status
59 March 16, 2022 Study Status
60 April 8, 2022 Study Status
61 April 23, 2022 Study Status
62 May 11, 2022 Study Status
63 June 17, 2022 Study Status
64 July 8, 2022 Study Status
65 August 9, 2022 Study Status
66 September 9, 2022 Study Status
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Study NCT02421939
Submitted Date:  April 16, 2015 (v1)

Open or close this module Study Identification
Unique Protocol ID: 2215-CL-0301
Brief Title: A Study of ASP2215 Versus Salvage Chemotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With FMS-like Tyrosine Kinase (FLT3) Mutation
Official Title: A Phase 3 Open-Label, Multicenter, Randomized Study of ASP2215 Versus Salvage Chemotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With FLT3 Mutation
Secondary IDs: 2015-000140-42 [EudraCT Number]
Open or close this module Study Status
Record Verification: April 2015
Overall Status: Not yet recruiting
Study Start: August 2015
Primary Completion: March 2020 [Anticipated]
Study Completion: March 2020 [Anticipated]
First Submitted: April 16, 2015
First Submitted that
Met QC Criteria:
April 16, 2015
First Posted: April 21, 2015 [Estimate]
Last Update Submitted that
Met QC Criteria:
April 16, 2015
Last Update Posted: April 21, 2015 [Estimate]
Open or close this module Sponsor/Collaborators
Sponsor: Astellas Pharma Global Development, Inc.
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring: Yes
Open or close this module Study Description
Brief Summary:

The purpose of this study is to determine the clinical benefit of ASP2215 therapy in patients with FMS-like tyrosine kinase (FLT3) mutated acute myeloid leukemia (AML) who are refractory to or have relapsed after first-line AML therapy as shown with overall survival compared to salvage chemotherapy.

This study will also determine the overall efficacy in event-free survival (EFS) and complete remission (CR) rate of ASP2215 compared to salvage chemotherapy.

Detailed Description:

Subjects will be randomized in a 2:1 ratio to receive ASP2215 or salvage chemotherapy. Subjects will enter the screening period up to 14 days prior to the start of treatment. Prior to randomization, a salvage chemotherapy regimen will be pre-selected for each subject; options will include low-dose cytarabine (LoDAC), azacitidine, mitoxantrone, etoposide, and intermediate-dose cytarabine (MEC), or fludarabine, cytarabine, and granulocyte colony-stimulating factor (G-CSF) with idarubicin (FLAG-IDA). The randomization will be stratified by response to first-line therapy and pre-selected salvage chemotherapy. Subjects will be administered treatment over continuous 28-day cycles.

Long term follow up will be done every 3 months up to 3 years from subject's end of treatment visit.

Open or close this module Conditions
Conditions: Leukemia, Acute Myeloid (AML)
Keywords: ASP2215
Acute Myeloid Leukemia (AML)
FLT3 Mutation
Relapsed Acute Myeloid Leukemia
Refractory Acute Myeloid Leukemia
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 3
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: None (Open Label)
Allocation: Randomized
Enrollment: 369 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: ASP2215
Administered once daily
Drug: ASP2215
tablet, oral
Active Comparator: Salvage chemotherapy
Options for salvage chemotherapy are limited to the following: Low- Dose Cytarabine (LoDAC), Azacitidine, MEC Induction Chemotherapy, FLAG-IDA Induction Chemotherapy
Drug: LoDAC (Low Dose Cytarabine)
subcutaneous (SC) or intravenous (IV) injection
Drug: Azacitidine
SC or IV injection
Drug: MEC (Mitoxantrone, Etoposide, Cytarabine)
IV injection
Drug: FLAG-IDA (Granulocyte-Colony Stimulating Factor (G-CSF), Fludarabine, Cytarabine, Idarubicin)
SC (G-CSF) and IV (Fludarabine, Cytarabine, Idarubicin) injection
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Overall Survival (OS)
[ Time Frame: up to 56 months ]

Secondary Outcome Measures:
1. Event-free survival
[ Time Frame: up to 56 months ]

2. Complete remission
[ Time Frame: up to 56 months ]

3. Leukemia-free survival
[ Time Frame: up to 56 months ]

4. Duration of remission
[ Time Frame: up to 55 months ]

5. Composite complete remission
[ Time Frame: up to 55 months ]

Complete remission (CR) + Complete remission with incomplete hematologic recovery (Cri) + Complete remission with incomplete platelet recovery (CRp)
6. Transplantation rate
[ Time Frame: up to 55 months ]

Transplantation rate is defined as the percentage of subjects undergoing Hematopoietic stem cell transplant (HSCT) during the study period.
7. Brief Fatigue Inventory
[ Time Frame: up to 20 months ]

The Brief Fatigue Inventory (BFI) is used to assess the severity of fatigue and the impact of fatigue on daily functioning in patients with fatigue due to cancer and cancer treatment. The BFI short form has 9 items and a 24-hour recall. A global fatigue score is computed by averaging the 9 items.
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  • Subject has a diagnosis of primary acute myeloid leukemia (AML) or AML secondary to myelodysplastic syndrome (MDS) according to WHO classification (2008) as determined by pathology review at the treating institute.
  • Subject is refractory to or relapsed after first-line AML therapy (with or without hematopoietic stem cell transplant (HSCT)).
    • Refractory to first-line AML therapy is defined as:

      1. Subject did not achieve complete remission/complete remission with incomplete hematologic recovery/complete remission with incomplete platelet recovery (CR/CRi/CRp) under initial therapy. A subject eligible for standard therapy must receive at least one cycle of an anthracycline containing induction block in standard dose for the selected induction regimen. A subject not eligible for standard therapy must have received at least one complete block of induction therapy seen as the optimum choice of therapy to induce remission for this subject.

    • Relapsed after first-line AML therapy. First line AML therapy is defined as (all criteria must be met):
      1. Subject achieved a CR/CRi/CRp as defined by Cheson criteria (2003);
      2. Initial AML therapy must have consisted of up to two induction blocks with or without consolidation or maintenance, with or without transplantation.
  • Subject is positive for FMS-like tyrosine kinase (FLT3) activating mutation in bone marrow or whole blood as determined by central lab.
  • Subject has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
  • Subject is eligible for pre-selected salvage chemotherapy.
  • Subject must meet the following criteria as indicated on the clinical laboratory tests:
    • Serum aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x upper limit of normal (ULN)
    • Serum total bilirubin ≤ 1.5 x ULN
    • Serum creatinine ≤ 1.5 x ULN or an estimated glomerular filtration rate of > 50 mL/min as calculated by the Modification of Diet in Renal Disease equation.
  • Subject is suitable for oral administration of study drug.
  • Female subject must either:
    • Be of non-child bearing potential:
      1. post-menopausal (defined as at least 1 year without any menses) prior to Screening, or
      2. documented surgically sterile (at least 1 month prior to Screening)
    • Or, if of childbearing potential,
      1. Agree not to try to become pregnant during the study and for 45 days after the final study administration
      2. And have a negative urine pregnancy test at Screening
      3. And, if heterosexually active, agree to consistently use two forms of highly effective birth control (at least one of which must be a barrier method) starting at Screening and throughout the study period and for 45 days after the final study drug administration.
  • Female subject must agree not to breastfeed at Screening and throughout the study period, and for 45 days after the final study drug administration.
  • Female subject must not donate ova starting at Screening and throughout the study period, and for 45 days after the final study drug administration.
  • Male subject and their female spouse/partners who are of childbearing potential must be using highly effective contraception consisting of two forms of birth control (at least one of which must be a barrier method) starting at Screening and continue throughout the study period, and for 105 days after the final study drug administration
  • Male subject must not donate sperm starting at Screening and throughout the study period and 105 days after the final study drug administration.
  • Subject agrees not to participate in another interventional study while on treatment.

Exclusion Criteria:

  • Subject was diagnosed as acute promyelocytic leukemia (APL).
  • Subject has BCR-ABL-positive leukemia (chronic myelogenous leukemia in blast crisis).
  • Subject has AML secondary to prior chemotherapy for other neoplasms (except for MDS).
  • Subject has AML that has relapsed after or is refractory to more than 1 line of therapy. A single line of therapy is defined as induction chemotherapy with or without consolidation (and consolidation may include HSCT). If the first induction cycle does not result in a CR or partial remission and the induction chemotherapy combination is changed, this is still counted as "one line of therapy," including consolidation/HSCT.
  • Subject has clinically active central nervous system leukemia.
  • Subject has been diagnosed with another malignancy, unless disease-free for at least 5 years. Subjects with treated nonmelanoma skin cancer, in situ carcinoma or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed. Subjects with organ-confined prostate cancer with no evidence of recurrent or progressive disease are eligible if hormonal therapy has been initiated or the malignancy has been surgically removed or treated with definitive radiotherapy.
  • Subject has received prior treatment with ASP2215 or other FLT3 inhibitors (with the exception of sorafenib used in first-line therapy regimen as part of induction, consolidation, and/or maintenance).
  • Subject has clinically significant abnormality of coagulation profile, such as disseminated intravascular coagulation (DIC).
  • Subject has had major surgery within 4 weeks prior to the first study dose.
  • Subject has radiation therapy within 4 weeks prior to the first study dose.
  • Subject has congestive heart failure New York Heart Association (NYHA) class 3 or 4, or subject with a history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram performed within 3 months prior to study entry results in a left ventricular ejection fraction that is ≥ 45%.
  • Subject requires treatment with concomitant drugs that are strong inducers of cytochrome P450 (CYP)3A4 or strong inhibitors or inducers of P-glycoprotein (P-gp) or substrates of multidrug and toxin extrusion protein 1 (MATE1) with the exception of drugs that are considered absolutely essential for the care of the subject.
  • Subject requires treatment with concomitant drugs that target serotonin 5-hydroxytryptamine receptor 1 (5HT1R) or 5-hydroxytryptamine receptor 2B (5HT2BR) or sigma nonspecific receptor with the exception of drugs that are considered absolutely essential for the care of the subject.
  • Subject has an active uncontrolled infection.
  • Subject is known to have human immunodeficiency virus infection.
  • Subject has active hepatitis B or C, or other active hepatic disorder.
  • Subject has any condition which makes the subject unsuitable for study participation.
Open or close this module Contacts/Locations
Central Contact Person: Astellas Pharma Global Development
Telephone: 800-888-7704 Ext. 5473
Email: Astellas.registration@astellas.com
Study Officials: Executive Medical Director
Study Director
Astellas Pharma Global Development, Inc.
Locations:
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Links:
Available IPD/Information:

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