HEAT-AML (Hydroxyurea-Enhanced Ara-C Treatment of Adult Acute Myeloid Leukaemia): A clinical study to assess whether addition of hydroxyurea to standard treatment against acute myeloid leukaemia (AML) is safe and efficacious

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Karolinska University Hospital

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

15 Jul 2019 → ongoing

Decision date (initial)

2024-03-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-509019-97-00

EudraCT number

2018-004050-16

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy

To assess the safety and tolerability of HU at three different doselevels added to standard AML therapy consisting of ara-C and daunorubicin (frequency and severity of toxicities; dose-finding).

To assess the effect of HU added to standard AML therapy consisting of ara-C and daunorubicin on the rate of negative minimal residual disease (MRD-negativity) after the second standard chemotherapy cycle

Secondary objectives 7

1. To assess the time to haematopoietic recovery after each chemotherapy treatment cycle
2. To assess the effect of HU added to standard AML therapy consisting of ara-C and daunorubicin on ara-CTP accumulation in peripheral blasts
3. To assess the effect of HU added to standard AML therapy on remission (CR/CRi/MLFS)
4. To assess the effect of HU added to standard AML therapy on eventfree survival (EFS)
5. To assess the effect of HU added to standard AML therapy on relapse-free survival (RFS) two years after diagnosis
6. To assess the effect of HU added to standard AML therapy on overall survival (OS) two years after diagnosis
7. To assess the role of SAMHD1 protein expression for secondary objectives 2-6

Conditions and MedDRA coding

Newly diagnosed acute myeloid leukaemia (AML) in patients ≥ 18 years of age

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 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
2. Patients 18 years and older.
3. 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
4. Male patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment.
5. Written informed consent.
6. Patient is capable of giving informed consent.

Exclusion criteria 10

1. Acute promyelocytic leukemia.
2. CNS leukaemia
3. Ongoing treatment with gemtuzumab-ozogamicin.
4. Major organ failure precluding administration of planned chemotherapy.
5. Glomerular filtration rate (GFR) < 30 ml/min
6. 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
7. Known intolerance to any of the chemotherapeutic drugs in the protocol.
8. Positive pregnancy test. Lactating female or female of childbearing potential not using adequate contraception.
9. Fanconi anaemia
10. Patients with a history of non-compliance to medical regimens or who are considered unreliable with respect to compliance.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 3

1. Safety and tolerability (frequency and severity of non-hematological toxicities).
2. 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.
3. Efficacy profile (response rate (CR, CRi, MLFS), event free survival (EFS), relapse-free survival (RFS), and overall survival (OS))

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Karolinska University Hospital

Sponsor organisation

Karolinska University Hospital

Address

Eugeniavagen 3

City

Solna

Postcode

171 64

Country

Sweden

Scientific contact point

Organisation

Karolinska University Hospital

Contact name

Nikolas Herold

Public contact point

Organisation

Karolinska University Hospital

Contact name

Nikolas Herold

Locations

1 EU/EEA country · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

1 submissions — initial application plus substantial / non-substantial modifications