R/R AMLPhase 1/2FLAsH-IV-AMLNCT07766850
Addition of Hydroxyurea to Fludarabine, Cytarabine, Idarubicin and Venetoclax Salvage Therapy for Adults With Relapsed or Refractory Acute Myeloid Leukemia
A Phase 1/2 study testing Hydroxycarbamid in people with R/R AML, run by Christer C Nilsson at 1 site in Sweden.
Trial summary
This study is evaluating a new treatment approach for adults with acute myeloid leukemia (AML) that has either returned after previous treatment or has not responded to treatment. Outcomes for these patients are often poor, and there is a need for more effective therapies. Read more about this study
- Who is it for?
- Ages 18 to 74 years
- Conditions the study is for
- R/R AML
- What is being tested?
- Hydroxycarbamid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteSweden
- Study dates
- Oct 2026to Sep 2034
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 74 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- A diagnosis of either:
- Refractory AML defined as having > 10% bone marrow blasts after induction with one cycle of intensive chemotherapy or no CR after two cycles of chemotherapy.
- Relapsed disease (including extramedullary disease) according to the 2022 ELN criteria (see appendix A).
- MRD relapse defined as evidence of measurable (minimal) residual disease (MRD) at a level of ≥5%, as determined by either molecular assays or multiparameter flow cytometry.
- Age 18 years or older.
- ECOG Performance Status ≤ 2.
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- Adequate renal and hepatic functions as indicated by the following laboratory values:
- Creatinine clearance ≥ 30 mL/min calculated by the Cockcroft Gault formula.
- Serum bilirubin ≤ 3 x upper limit of normal (ULN), unless due to Gilbert's syndrome.
- Alanine aminotransferase (ALAT) ≤ 5 x ULN.
- Considered fit for intensive chemotherapy.
- Male patients must use a latex condom during any sexual contact with women of childbearing potential, even if they have undergone a successful vasectomy and must agree to avoid fathering a child (while on therapy and for 6 months after the final study drug administration). In addition, their female partners of childbearing potential must use a highly effective method of birth control.
- Male patient must not donate sperm starting at screening and throughout the study period and for 6 months after the final study drug administration.
- Female patients of nonchildbearing potential must be postmenopausal (defined as at least 1 year without any menses), documented surgically sterile prior to screening.
- Female patients of childbearing potential must agree to avoid pregnancy during the study and for 6 months after the final study drug administration and have a negative urine or serum pregnancy test at screening, and if heterosexually active, agree to consistently apply one highly effective method of birth control in combination to a barrier method for the duration of the study and for 6 months after the final study drug administration.
- The subject has given their written consent to participate in the trial.
- Patient is capable of giving informed consent.
Who cannot join
- Acute promyelocytic leukemia.
- WBC ≥30; pretreatment with HU to reduce the level of WBC <30 is allowed in part B/phase II of the trial.
- TP53 double hit mutation / biallelic TP53 inactivation.
- CNS leukemia.
- Relapse within 3 months from the date of allo-HCT.
- Uncontrolled infection.
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- ECOG Performance Status > 2.
- Major organ failure precluding administration of planned chemotherapy
- Cardiac dysfunction as defined by:
- Myocardial infarction within the last 3 months of study entry, or
- Reduced left ventricular function with an ejection fraction < 50% as measured by echocardiogram (will only be performed when clinically suspected) or
- Unstable angina or
- New York Heart Association (NYHA) grade III or IV congestive heart failure (see appendix C) or
- Severe cardiac arrhythmias
- Age 75 years or older.
- Known intolerance to any of the chemotherapeutic drugs in the protocol.
- Positive pregnancy test.
- Lactating female or female of childbearing potential not using adequate contraception.
- Known inherited bone marrow failure syndromes (e.g., Fanconi anemia, Dyskeratosis congenita and related telomeropathies (e.g., TERT, TERC, DKC1 mutations).
- Patients with a history of non-compliance to medical regimens or who are considered unreliable with respect to compliance.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Sweden1 site
Medical Unit Hematology, Karolinska University Hospital
Stockholm
Merja Jansson, +46 8 123 827 08, merja.jansson@regionstockholm.se
Christer C Nilsson, MD PhD
About this study
Official title: FLAsH-IV-AML: A Phase I/II Multi-center Study to Assess the Tolerability and Efficacy of the Addition of Hydroxyurea to Salvage Treatment With Fludarabine, Ara-C, Idarubicin and Venetoclax for Adults With Relapsed or Refractory Acute Myeloid Leukemia
This study is evaluating a new treatment approach for adults with acute myeloid leukemia (AML) that has either returned after previous treatment or has not responded to treatment. Outcomes for these patients are often poor, and there is a need for more effective therapies.
The study is investigating whether adding hydroxyurea to a combination of established AML medicines (fludarabine, cytarabine, idarubicin, and venetoclax) is safe and tolerable and can improve treatment results. Laboratory studies suggest that hydroxyurea may help leukemia cells become more sensitive to treatment and may increase the effectiveness of chemotherapy.
Read more
The study is being conducted in two parts. In the first part, researchers will determine the safest and most appropriate dose of hydroxyurea when given together with the study treatment. In the second part, researchers will evaluate whether adding hydroxyurea improves treatment outcomes, including the length of time patients remain free from disease progression, relapse, or death.
The overall goal of the study is to determine whether adding hydroxyurea to standard treatment for relapsed or refractory AML is safe and may improve patient outcomes.
- Conditions
- R/R AML
- Being tested
- Hydroxycarbamid
- Keywords
- Hydroxyurea, FLAG-Ida, Venetoclax
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HydroxycarbamidDrug
Also called Hydroxyurea
Hydroxyurea 500-1000 mg administered 1 hour before each infusion of cytarabine.
| Study group | Role | What they receive |
|---|---|---|
| Hydroxyurea added to fludarabine, ara-C, idarubicin and venetoclax | Experimental | Hydroxyurea added to fludarabine, ara-C, idarubicin and venetoclax Receives: Drug: Hydroxycarbamid |
What is being measured
The primary outcome is the main question the study is designed to answer.
1-year EFS
Defined as event-free-survial from the time from initiation of study treatment to the first occurrence of treatment failure, hematologic relapse from CR/CRi, or death from any cause.
Measured: From initiation of study treatment to the first occurrence of treatment failure, hematologic relapse after CR/CRi, or death from any cause, whichever occurs first, assessed up to 365 days.
Secondary outcomes (9)
Safety and tolerability: incidence and severity of treatment-emergent adverse events
Frequency, nature and severity of non-hematological toxicities, including potential ara-C or fludarabine related neurological or dermatological adverse events.
Measured: From registration in the study until 60 days after the last dose of treatment.
Overall survival (OS)
Overall survival (OS), defined as the time from initiation of study treatment to death from any cause, with survival estimates reported at 1 and 2 years after initiation of study treatment.
Measured: From initiation of study treatment through 2 years of follow-up.
2-year event-free survival (EFS)
Time from initiation of study treatment to the first occurrence of treatment failure, hematologic relapse after CR/CRi, or death from any cause, whichever occurs first.
Measured: From initiation of study treatment through 2 years of follow-up.
Relapse-free survival (RFS)
Overall survival (OS), defined as the time from initiation of study treatment to the date of death from any cause or hematologic relapse from CR/CRi, with survival estimates reported at 1 and 2 years after initiation of study treatment.
Measured: From initiation of study treatment through 2 years of follow-up.
Cumulative incidence of hematologic relapse
Cumulative incidence of hematologic relapse after achievement of CR/CRi, reported at 1 and 2 years. Death without prior relapse will be treated as a competing risk.
Measured: From initiation of study treatment through 2 years of follow-up.
Response rate
Proportion of patients achieving complete remission (CR), complete remission with incomplete hematologic recovery (CRi), morphologic leukemia-free state (MLFS), partial remission (PR) and minimal residual disease (MRD) negativity.
Measured: At response assessment after Cycle 1 (between Day 25 and Day 35 from the start of Cycle 1).
Time to hematopoietic recovery
Time to hematopoietic recovery (ANC 0.5 and 1.0 x 109/L; platelets 50 and 100 x 109/L) after each chemotherapy treatment cycle, defined as the time from the start of the cycle until recovery.
Measured: From the start of each treatment cycle until hematopoietic recovery. Treatment cycles are of variable duration, with no predefined cycle length; the subsequent cycle is initiated only after hematopoietic recovery.
Rate of patients bridged to allo-HCT
Proportion of patients undergoing allogeneic hematopoietic cell transplantation.
Measured: From treatment initiation until allogeneic hematopoietic cell transplantation, relapse/progression, death, or 2 years of follow-up, whichever occurs first.
Early mortality (30-day and 60-day mortality)
Proportion of patients who die from any cause within 30 and 60 days after initiation of study treatment.
Measured: 30 and 60 days after initiation of study treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2026
- Study startOct 2026 (estimated)
- Primary completionJun 2029 (estimated)
- Study completionSep 2034 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for R/R AMLStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- A non-randomized open label phase I/II multi-center study
- Masking
- None (open label)
- Enrolment
- 26 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Christer C Nilsson
- Sponsor type
- Other government
- Collaborators
- Karolinska University Hospital
- Responsible party
- Sponsor-investigator, Christer C Nilsson, Region Stockholm
- Investigators
- Christer C Nilsson, MD PhD, Principal investigator, Karolinska University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07766850
- Sponsor's protocol ID
- FLAsH-IV-AML
- Acronym
- FLAsH-IV-AML
- Status last verified
- Aug 2026
- First submitted
- 12 Jun 2026
- Last updated
- 17 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: IPD Sharing Statement: Individual participant data (IPD) will not be shared. Justification: The study is an early-phase investigator-initiated clinical trial in a rare and high-risk patient population. Due to the small sample size, detailed molecular data, and potential risk of re-identification despite de-identification, individual participant data will not be made publicly available.
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- FLAsH-IV-AML: A Phase I/II Multi-center Study to Assess the Tolerability and Efficacy of the Addition of Hydroxyurea to Salvage Treatment With Fludarabine, Ara-C, Idarubicin and Venetoclax for Adults With Relapsed or Refractory Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT07766850
- Acronym / sponsor ID
- FLAsH-IV-AML / FLAsH-IV-AML
- Conditions
- R/R AML
- Keywords
- Hydroxyurea, FLAG-Ida, Venetoclax
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 26 participants (estimated)
- Lead sponsor
- Christer C NilssonOther government
- Collaborators
- Karolinska University Hospital
- Study start
- Oct 2026 (estimated)
- Primary completion
- Jun 2029 (estimated)
- Study completion
- Sep 2034 (estimated)
- First posted
- 17 Aug 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is evaluating a new treatment approach for adults with acute myeloid leukemia (AML) that has either returned after previous treatment or has not responded to treatment. Outcomes for these patients are often poor, and there is a need for more effective therapies.
The study is investigating whether adding hydroxyurea to a combination of established AML medicines (fludarabine, cytarabine, idarubicin, and venetoclax) is safe and tolerable and can improve treatment results. Laboratory studies suggest that hydroxyurea may help leukemia cells become more sensitive to treatment and may increase the effectiveness of chemotherapy.
The study is being conducted in two parts. In the first part, researchers will determine the safest and most appropriate dose of hydroxyurea when given together with the study treatment. In the second part, researchers will evaluate whether adding hydroxyurea improves treatment outcomes, including the length of time patients remain free from disease progression, relapse, or death.
The overall goal of the study is to determine whether adding hydroxyurea to standard treatment for relapsed or refractory AML is safe and may improve patient outcomes.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- A non-randomized open label phase I/II multi-center study
| Arm | Type | Receives |
|---|---|---|
| Hydroxyurea added to fludarabine, ara-C, idarubicin and venetoclax | Experimental | Drug: HydroxycarbamidHydroxyurea added to fludarabine, ara-C, idarubicin and venetoclax |
Who may qualify
- Ages
- 18 to 74 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- A diagnosis of either:
- Age 18 years or older.
- ECOG Performance Status ≤ 2.
- Adequate renal and hepatic functions as indicated by the following laboratory values:
- Considered fit for intensive chemotherapy.
Key exclusion criteria (20 listed)
- Acute promyelocytic leukemia.
- WBC ≥30; pretreatment with HU to reduce the level of WBC <30 is allowed in part B/phase II of the trial.
- TP53 double hit mutation / biallelic TP53 inactivation.
- CNS leukemia.
- Relapse within 3 months from the date of allo-HCT.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HydroxycarbamidAlso: HydroxyureaHydroxyurea 500-1000 mg administered 1 hour before each infusion of cytarabine. | Drug | Hydroxyurea added to fludarabine, ara-C, idarubicin and venetoclax |
Primary outcome
1-year EFS
Time frame: From initiation of study treatment to the first occurrence of treatment failure, hematologic relapse after CR/CRi, or death from any cause, whichever occurs first, assessed up to 365 days.
Defined as event-free-survial from the time from initiation of study treatment to the first occurrence of treatment failure, hematologic relapse from CR/CRi, or death from any cause.
9 secondary outcomes
Safety and tolerability: incidence and severity of treatment-emergent adverse events
Time frame: From registration in the study until 60 days after the last dose of treatment.
Overall survival (OS)
Time frame: From initiation of study treatment through 2 years of follow-up.
2-year event-free survival (EFS)
Time frame: From initiation of study treatment through 2 years of follow-up.
Relapse-free survival (RFS)
Time frame: From initiation of study treatment through 2 years of follow-up.
Cumulative incidence of hematologic relapse
Time frame: From initiation of study treatment through 2 years of follow-up.
Response rate
Time frame: At response assessment after Cycle 1 (between Day 25 and Day 35 from the start of Cycle 1).
Time to hematopoietic recovery
Time frame: From the start of each treatment cycle until hematopoietic recovery. Treatment cycles are of variable duration, with no predefined cycle length; the subsequent cycle is initiated only after hematopoietic recovery.
Rate of patients bridged to allo-HCT
Time frame: From treatment initiation until allogeneic hematopoietic cell transplantation, relapse/progression, death, or 2 years of follow-up, whichever occurs first.
Early mortality (30-day and 60-day mortality)
Time frame: 30 and 60 days after initiation of study treatment.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2026.
- Individual participant dataSharing planned: No. IPD Sharing Statement: Individual participant data (IPD) will not be shared. Justification: The study is an early-phase investigator-initiated clinical trial in a rare and high-risk patient population. Due to the small sample size, detailed molecular data, and potential risk of re-identification despite de-identification, individual participant data will not be made publicly available.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Christer C Nilsson, MD PhD principal investigator
Karolinska University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Hydroxycarbamid in people with R/R AML, run by Christer C Nilsson at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 17 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Christer C Nilsson, Md PhD (08-123 800 00, christer.c.nilsson@regionstockholm.se), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
1-year EFS (time frame: From initiation of study treatment to the first occurrence of treatment failure, hematologic relapse after CR/CRi, or death from any cause, whichever occurs first, assessed up to 365 days.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2026.