Clinical trial • Phase I/II • Haematology
HYDROXYCARBAMIDE for Acute myeloid leukaemia (AML) - newly diagnosed
Phase I/II trial of HYDROXYCARBAMIDE for Acute myeloid leukaemia (AML) - newly diagnosed.
Overview
- Trial Therapeutic Area
- Haematology
- Trial Disease
- Acute myeloid leukaemia (AML) - newly diagnosed
- Trial Stage
- Phase I/II
- Drug Modality
- Small molecule
Key dates
- Initial CTIS Submission Date
- 28-02-2024
- First CTIS Authorization Date
- 18-03-2024
Trial design
Standard ara-C (cytarabine) and daunorubicin-based therapy (standard AML therapy). Hydroxyurea (HU) is added to standard therapy; no specific comparator arm dosing/schedule detailed.-controlled, adaptive Phase I/II trial across 11 sites in Sweden.
- Comparator
- Standard ara-C (cytarabine) and daunorubicin-based therapy (standard AML therapy). Hydroxyurea (HU) is added to standard therapy; no specific comparator arm dosing/schedule detailed.
- Adaptive
- True - dose-finding design with assessment of HU at three different dose levels added to standard AML therapy; specific escalation rules, interim analyses or stopping rules are not provided in the record.
- Single Multiple Or Escalation Dose Combined
- Yes
- Target Sample Size
- 69
Eligibility
Recruits 69 Vulnerable population selected. Participants are adults (18+). "Written informed consent." is required and "Patient is capable of giving informed consent." No assent procedures or paediatric consent documents are described..
- Pregnancy Exclusion
- Positive pregnancy test. Lactating female or female of childbearing potential not using adequate contraception.
- Vulnerable Population
- Vulnerable population selected. Participants are adults (18+). "Written informed consent." is required and "Patient is capable of giving informed consent." No assent procedures or paediatric consent documents are described.
Inclusion criteria
- {"criterion_text":"- diagnosis of AML and related myeloid precursor neoplasia according to WHO 2008 classification (excluding acute promyelocytic leukemia) including secondary AML (after an antecedent hematological disease (e.g. MDS) and therapy-related AML, or acute leukaemia of ambiguous lineage according to WHO 2008)\n- Patients 18 years and older.\n- Adequate renal and hepatic functions unless clearly disease related as indicated by the following laboratory values: Serum creatinine ≤ 220 μmol/L, unless considered AML-related; Serum bilirubin ≤ 2.5 x upper limit of normal (ULN, i.e. ≤65 μmol/L), unless considered AML-related or due to Gilbert's syndrome; Alanine aminotransferase (ALAT) ≤ 2.5 x ULN, i.e. ≤ 1.9 μcat/L and ≤ 2.9 for females and males, respectively, unless considered AML-related\n- Male patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment.\n- Written informed consent.\n- Patient is capable of giving informed consent."}
Exclusion criteria
- {"criterion_text":"- Acute promyelocytic leukemia.\n- Patients with a history of non-compliance to medical regimens or who are considered unreliable with respect to compliance.\n- CNS leukaemia\n- Ongoing treatment with gemtuzumab-ozogamicin.\n- Major organ failure precluding administration of planned chemotherapy.\n- Glomerular filtration rate (GFR) < 30 ml/min\n- Cardiac dysfunction as defined by: Myocardial infarction within the last 3 months of study entry, or; Reduced left ventricular function with an ejection fraction < 40% as measured by echocardiogram (will only be performed when clinically suspected) or; Unstable angina or; New York Heart Association (NYHA) grade IV congestive heart failure or; Unstable cardiac arrhythmias\n- Known intolerance to any of the chemotherapeutic drugs in the protocol.\n- Positive pregnancy test. Lactating female or female of childbearing potential not using adequate contraception.\n- Fanconi anaemia"}
Endpoints
Primary endpoints
- {"endpoint_text":"- MRD-negativity after cycle 2. Defined as malignant blasts as a percentage of total bonemarrow cells and as a percentage of the whole white blood cell compartment. These percentages are calculated based on the frequency of cells with an aberrant phenotype.","definition_or_measurement_approach":"Defined as malignant blasts as a percentage of total bone marrow cells and as a percentage of the whole white blood cell compartment; percentages calculated based on the frequency of cells with an aberrant phenotype."}
Secondary endpoints
- {"endpoint_text":"- Safety and tolerability (frequency and severity of non-hematological toxicities).","definition_or_measurement_approach":"Assessment of frequency and severity of non-hematological toxicities (no further measurement details provided)."}
- {"endpoint_text":"- Time to hematopoietic recovery (ANC 0.5 and 1.0 x 109/L; platelets 50 x 109/L) after each chemotherapy treatment cycle, defined as the time from the start of the cycle until recovery.","definition_or_measurement_approach":"Defined as time from the start of the cycle until recovery to ANC 0.5 and 1.0 x10^9/L and platelets 50 x10^9/L."}
- {"endpoint_text":"- Efficacy profile (response rate (CR, CRi, MLFS), event free survival (EFS), relapse-free survival (RFS), and overall survival (OS))","definition_or_measurement_approach":"Includes response rates (CR, CRi, MLFS) and time-to-event measures EFS, RFS, and OS (no additional measurement details provided)."}
Recruitment
- Planned Sample Size
- 69
- Recruitment Window Months
- 99
- Consent Approach
- Written informed consent is required. Patients must be capable of giving informed consent. Participants are adults (≥18). No paediatric assent procedures or language-specific consent documents are described.
Geography
- Total Number Of Sites
- 11
- Total Number Of Participants
- 69
Sweden
- Earliest CTIS Part Ii Submission Date
- 20-10-2023
- Latest Decision Or Authorization Date
- 18-03-2024
- Processing Time Days
- 150
- Number Of Sites
- 11
- Number Of Participants
- 69
Sites
- Site Name
- Sahlgrenska University Hospital-Vastra Gotalandsregionen
- Department Name
- Department of Hematology
- Contact Person Name
- Lars Möllgård
- Contact Person Email
- lars.mollgard@vgregion.se
- Site Name
- Region Oerebro Laen
- Department Name
- Department of Hematology
- Contact Person Name
- Bertil Uggla
- Contact Person Email
- bertil.uggla@regionorebrolan.se
- Site Name
- Region Skane Skanes Universitetssjukhus
- Department Name
- Department of Hematology
- Contact Person Name
- Vladimir Lazarevic
- Contact Person Email
- vladimir.lazarevic@med.lu.se
- Site Name
- Uppsala University Hospital
- Department Name
- Department of Hematology
- Contact Person Name
- Anna Robelius
- Contact Person Email
- anna.robelius@uu.se
- Site Name
- Karolinska University Hospital
- Department Name
- Department of hematology
- Contact Person Name
- Martin Jädersten
- Contact Person Email
- martin.jadersten@regionstockholm.se
- Site Name
- Linkoping University Hospital Region Ostergotland
- Department Name
- Department of hematology
- Contact Person Name
- Petter Willner Hjelm
- Contact Person Email
- petter.willner.hjelm@regionostergotland.se
- Site Name
- Region Halland
- Department Name
- Department of Hematology
- Contact Person Name
- Nevzeta Kuric
- Contact Person Email
- nevzeta.kuric@regionhalland.se
- Site Name
- Region Norrbotten
- Department Name
- Department of hematology
- Contact Person Name
- Kristina Myhr-eriksson
- Contact Person Email
- kristina.myhr-eriksson@norrbotten.se
- Site Name
- Region Dalarna
- Department Name
- Department of Hematology
- Contact Person Name
- Max Flogegård
- Contact Person Email
- max.flogegard@regiondalarna.se
- Site Name
- Skaraborg Hospital-Vastra Gotalandsregionen
- Department Name
- Department of Hematology
- Contact Person Name
- Christian Scharenberg
- Contact Person Email
- christian.scharenberg@vgregion.se
- Site Name
- Region Vaesterbotten
- Department Name
- Department of Hematology
- Contact Person Name
- Anna Thunström Salzer
- Contact Person Email
- anna.thunstrom@regionvasterbotten.se
Sponsor
Primary sponsor
- Full Name
- Karolinska University Hospital
- Organisation Type
- Hospital/Clinic/Other health care facility
- Country Of Registered Address
- Sweden
Investigational products
- Investigational Product Name
- Hydroxycarbamide medac 500 mg capsule, hard
- Active Substance
- HYDROXYCARBAMIDE
- Modality
- Small molecule
- Routes Of Administration
- ORAL USE
- Route
- oral
- Authorisation Status
- Marketing authorisation PL 11587/0019 (prodAuthStatus 2)
- Investigational Product Name
- Cytarabine STADA 20 mg/ml injektionsvätska, lösning
- Active Substance
- CYTARABINE
- Modality
- Small molecule
- Routes Of Administration
- INTRAVENOUS USE
- Route
- intravenous
- Authorisation Status
- Marketing authorisation 16725 (prodAuthStatus 2)
- Investigational Product Name
- Cerubidin 20 mg pulver till infusionsvätska, lösning
- Active Substance
- DAUNORUBICIN
- Modality
- Small molecule
- Routes Of Administration
- INTRAVENOUS USE
- Route
- intravenous
- Authorisation Status
- Marketing authorisation 9244 (prodAuthStatus 2)
- Combination Treatment
- Yes
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