AML According to WHO 2016 Classification (Except Acute Promyelocytic Leukemia) AND (Refractory to Induction Therapy OR Relapsed After First Line Treatment)Phase 2Q-HAMNCT03989713
Quizartinib and High-dose Ara-C Plus Mitoxantrone in Relapsed/Refractory AML With FLT3-ITD
A Phase 2 study testing MRD-triggered arm and Prophylactic Arm in people with AML According to WHO 2016 Classification (Except Acute Promyelocytic Leukemia) AND (Refractory to Induction Therapy OR Relapsed After First Line Treatment), run by Prof. Dr. Richard F Schlenk at 1 site in Germany.
Trial summary
In this multicenter, upfront randomized phase II trial, all patients receive quizartinib in combination with HAM (high-dose cytarabine, mitoxantrone) during salvage therapy. Efficacy is assessed by comparison to historical controls based on the matched threshold crossing approach. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- AML According to WHO 2016 Classification (Except Acute Promyelocytic Leukemia) AND (Refractory to Induction Therapy OR Relapsed After First Line Treatment)
- What is being tested?
- MRD-triggered arm and Prophylactic Arm
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteGermany
- Study dates
- 17 Jul 2020to 11 Sep 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with acute myeloid leukemia according to the 2016 WHO classification (except acute promyelocytic leukemia) who are either A) refractory to induction therapy or B) relapsed after first line treatment including chemotherapy, autologous and/or allo-HCT (details below).
- Positive for FLT3-ITD (defined as a ratio of mutant to wild-type alleles of at least 0.05; measured within 2 weeks before inclusion)
- ECOG performance status ≤ 2. See appendix 18.1
- Adequate renal function defined as creatinine clearance >50 mL/min (calculated using the standard method for the institution)
- Discontinuation of prior AML treatment for at least A) 10 days for cytotoxic agents and B) 28 days for investigational drug treatment before the start of study treatment (except hydroxyurea or other treatment to control hyperleukocytosis)
- Age ≥ 18 years, no upper age limit
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- Pregnancy and childbearing potential:
- Non-pregnant and non-nursing women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within a sensitivity of at least 25 mIU/mL within 72 hours prior to registration ("Women of childbearing potential" is defined as a sexually active mature woman who has not undergone a hysterectomy or who has had menses at any time in the preceding 24 consecutive months).
- Female patients of reproductive age must agree to avoid getting pregnant while on therapy.
- WOCBP must either commit to continued abstinence from heterosexual intercourse or begin one acceptable method of birth control (IUD, tubal ligation, or partner's vasectomy) during study and 6 months after end of study/treatment. Hormonal contraception is an inadequate method of birth control.
- Men 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 to father a child during study and 6 months after end of study/treatment
- Signed written informed consent
- Ability of patient to understand character and consequences of the clinical trial
- Refractory to induction therapy is defined as no CR, or CRi, or PR (according to standard criteria) [1] after 1 or 2 intensive induction cycles of at least 7 days of cytarabine 100-200mg/m² continuously or an equivalent regimen with cytarabine with total dose not less than 700mg/m² per cycle and 2 days of an anthracycline (e.g. daunorubicin, idarubicin).
- Relapsed after first line therapy is defined as relapsed AML (according to standard criteria) [1] after a first line therapy including at least one intensive induction and consolidation therapy including (but not limited to) allo-HCT.
Who cannot join
- Acute promyelocytic leukemia (AML FAB M3 with t(15;17)(q22;q12) / PML-RARA)
- Patients with known CNS leukemia
- Isolated extramedullary manifestation of AML
- Patients with a "currently active" second malignancy other than non-melanoma skin cancer. Patients are not considered to have a "currently active" malignancy if they have completed therapy for more than one year and are considered by their physician to be at less than 30% risk of relapse within one year
- Hyperleukocytosis (leukocytes > 30,000/µl) at the time of study entry. 1)
- Uncontrolled or significant cardiovascular disease, including any of the following:
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- History of heart failure NYHA class 3 or 4
- Left ventricular ejection fraction (LVEF) ≤ 40% by echocardiogram (ECHO)
- History of uncontrolled angina pectoris or myocardial infarction within 12 months prior to screening
- History of second (Mobitz II) or third degree heart block or any cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted)
- Inadequate liver function: ALT and AST ≥ 2.5 x ULN), total bilirubin ≥ 1.5 x ULN; Alkaline phosphatase ≥ 2.5 x ULN. Known liver cirrhosis or history of veno-occlusive disease (VOD) or history of Sinusoidal Obstruction Syndrome (SOS)
- Known positivity for HIV, active HBV, HCV or hepatitis A infection (active hepatitis B defined by HBs Ag positivity, active hepatitis C defined by positive virus load)
- Uncontrolled active infection
- Evidence or history of severe non-leukemia associated bleeding diathesis or coagulopathy
- within 100 days after allo-HCTat the time of screening
- clinically relevant Graft-versus-Host-Disease (GvHD) requiring initiation of treatment or treatment escalation within 21 days prior to screening
- Any one of the following ongoing or in the previous 6 months: myocardial infarction, congenital long QT syndrome, Torsades de pointes, arrhythmias (including sustained ventricular tachyarrhythmia), right or left bundle branch block and bifascicular block, unstable angina, coronary/peripheral artery bypass graft, cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolism; as well as bradycardia defined as <50 bpms
- QTc interval >470 msec using the Fredericia correction (QTcF).
- Patients known to be refractory to platelet or packed red cell transfusions as per institutional guidelines, or who are known to refuse or who are likely to refuse blood product support.
- Severe neurologic or psychiatric disorder interfering with ability of giving informed consent
- Known or suspected active alcohol or drug abuse
- No consent for biobanking and for registration, storage and processing of the individual disease-characteristics and course as well as information of the family physician about study participation.
- Pregnancy and lactation
- History of hypersensitivity to the investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product
- Prior treatment with quizartinib
- These patients should be treated with hydroxyurea and / or receive leukocytapheresis treatment according to routine practice and are only allowed to enter into the study when leukocyte counts of 30,000/µl or below are reached. If hydroxyurea is not sufficient to control hyperleukocytosis, i.v. application of 100mg cytarabine continuously over 24 hours may be discussed with the Principle Investigator or the Medical Coordinator.
Trial locations and contacts
1 site in 1 country.
Germany1 site
University Hospital Heidelberg Med5
Heidelberg, Baden-Wurttemberg, 69124
About this study
In this multicenter, upfront randomized phase II trial, all patients receive quizartinib in combination with HAM (high-dose cytarabine, mitoxantrone) during salvage therapy. Efficacy is assessed by comparison to historical controls based on the matched threshold crossing approach. During consolidation therapy (chemotherapy as well as allo-HCT) patients receive either prophylactic quizartinib therapy or MRD-triggered preemptive continuation therapy with quizartinib according to up-front randomization.
Read the detailed description
Acute myeloid leukemia (AML) is a clonal malignant disorder which is characterized by the expansion of leukemic blasts in the bone marrow and the peripheral blood, which goes along with a suppression of normal hematopoiesis including granulopoiesis, erythropoiesis and thrombocytopoiesis. The prognosis is largely determined by cytogenetic and molecular risk factors, age, performance status and antecedent myelodysplastic syndrome (MDS). With the exception of old and frail patients, most AML patients are eligible for intensive chemotherapy, which is given in curative intent consisting of induction and consolidation therapy. However, despite intensive therapy, the long-term outcome of AML patients remains poor, with less than 30% of patients achieving long lasting remission and even cure. This poor outcome is largely due to refractoriness to induction chemotherapy as well as relapses during and after completion of intensive induction and consolidation therapy. Regarding refractoriness, about 20-30% of AML patients under the age of 60 years and about 50% of older patients fail to attain complete remission (CR) following cytarabine plus anthracycline based standard induction therapy. In addition, patients having achieved CR are at a high risk of relapse, particularly within the first two years after completion of chemotherapy. Allogeneic hematopoietic cell transplantation (allo-HCT) is currently the only treatment strategy to offer the prospect of cure in relapsed/refractory (r/r)-AML; but outcome after allo-HCT is largely determined by the remission state before allo-HCT. With the aim to induce a CR before allo-HCT, salvage chemotherapy regimens are administered in r/r-AML. Typically, these salvage regimens are based on high dose cytarabine (HiDAC), which is frequently combined with either mitoxantrone (HAM regimen) or fludarabine plus idarubicin (idaFLA regimen). However, there is still no commonly accepted standard salvage regimen and overall CR rates remain low with less than one third of the patients achieving a CR. Apart from already known clinical unfavorable prognostic parameters in relapsed AML such as short first CR duration, older age and previous allo-HCT, FLT3-ITD has consistently been identified as an unfavorable molecular marker in both relapsed and refractory AML. Recently midostaurin has been approved by the FDA and EMA for the treatment of newly diagnosed AML with activating FLT3 mutations. But still roughly one quarter of patients, who received midostaurin, was refractory to induction therapy and relapse rate at 2 years excited 40%. Thus, new treatment options are urgently needed, particularly in r/r-AML with FLT3-ITD.
The oral second-generation bis-aryl urea tyrosine kinase inhibitor quizartinib is very specific for FLT3, has a high capacity for sustained FLT3 inhibition and an acceptable toxicity profile. Furthermore, single agent quizartinib doubled the response rate as compared to standard of care in a randomized study in r/r-AML. Although survival was also improved in this study the difference was only marginal.
In this protocol we evaluate the efficacy of quizartinib in combination with HAM (high-dose cytarabine, mitoxantrone) as compared to historical controls based on the matched threshold crossing approach followed by randomized prophylactic versus MRD-triggered continuation therapy with quizartinib including consolidation (chemotherapy as well as allo-HCT) and maintenance.
- Being tested
- MRD-triggered arm, Prophylactic Arm
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MRD-triggered armDrug
- Salvage therapy: Quizartinib: 40mg, p.o., Days: 4 - 21 Cytarabine: 18-60yrs: 3g/m² bid / >-60yrs: 1g/m² bid, i.v. 3h i.v. 3h, Days: 1,2,3; Mitoxantrone: 10mg, i.v. 30min: Days: 2,3;
- Consolidation therapy: Cytarabine: 18-60yrs: 3g/m² bid, i.v. 3h / >-60yrs: 1g/m² bid, i.v. 3h, Days: 1,2,3; Mitoxantrone: 10mg, i.v. 30min, Days: 2,3
- Observation therapy:
No treatment
Prophylactic ArmDrug
- Salvage therapy: Quizartinib: 40mg, p.o., Days: 4 - 21 Cytarabine: 18-60yrs: 3g/m² bid / >-60yrs: 1g/m² bid, i.v. 3h i.v. 3h, Days: 1,2,3; Mitoxantrone: 10mg, i.v. 30min: Days: 2,3;
- Consolidation therapy: Quizartinib: 40mg, p.o., Days: 4 - 21 Cytarabine: 18-60yrs: 3g/m² bid, i.v. 3h / >-60yrs: 1g/m² bid, i.v. 3h, Days: 1,2,3; Mitoxantrone: 10mg, i.v. 30min, Days: 2,3;
- Maintenance therapy:
Quizartinib: Cycle 1, Days 1-15: 40mg, p.o. and Day 16-28: 60mg, p.o.
| Study group | Role | What they receive |
|---|---|---|
| MRD-triggered arm | Experimental | 1. Salvage therapy: All patients are randomized upfront and receive one cycle Q-HAM salvage therapy. All patients achieving CR or CRi are allocated according to randomization to either MRD-triggered or prophylactic arm.
(Duration: one cycle á 21 days followed by up to 3 weeks recovery period if needed, 22-42 days in total)
2. Consolidation therapy: Patients receive one cycle of HAM and are further allocated based on the MRD-results assessed by flow cytometry with a cut of level of 0.1%: if the MRD is negative they remain in the MRD-triggered arm, whereas MRD positive patients cross over to the prophylactic arm.
(Up to 2 cycles. Duration: two cycles á 28 days each followed by up to two weeks recovery period if needed, 56-84 days in total.)
3. Observation: No treatment will be given in the MRD-triggered arm. (Duration: 48 weeks in total.)
4. Safety follow-up and observational follow-up Receives: Drug: MRD-triggered arm |
| Prophylactic Arm | Experimental | 1. Salvage therapy: All patients are randomized upfront and receive one cycle Q-HAM salvage therapy. All patients achieving CR or CRi are allocated according to randomization to either MRD-triggered or prophylactic arm.
(Duration: one cycle á 21 days followed by up to 3 weeks recovery period if needed, 22-42 days in total)
2. Consolidation therapy: Patients may receive up to two cycle of Q-HAM. (Up to 2 cycles. Duration: two cycles á 28 days each followed by up to two weeks recovery period if needed, 56-84 days in total.)
3. Maintenance therapy: Quizartinib will be given as single-agent therapy. The dose of quizartinib is aimed to be increased during maintenance therapy. (Up to 12 cycles. Duration: four times three cycles á 28 days, 48 weeks in total.)
4. Safety follow-up and observational follow-up Receives: Drug: Prophylactic Arm |
What is being measured
The primary outcome is the main question the study is designed to answer.
CRR
Composite remission rate defined as the proportion of patients experiencing a CR (Complete remission)/CRi (Complete remission with incomplete hematological recovery rate) after salvage therapy.
Measured: Collected during the first MRD-analysis / after approximately 100 study days
Secondary outcomes (6)
EFS
Event-free survival
Measured: Collected at a minimum at baseline, day 22 of Salvage therapy, last day of second cycle of consolidation therapy, 3-monthly during maintenance therapy, at EOT, 3-monthly during FU, and yearly after 2 years during FU, at EOS
RFS
Relapse-free survival
Measured: Collected at a minimum at baseline, day 22 of Salvage therapy, last day of second cycle of consolidation therapy, 3-monthly during maintenance therapy, at EOT, 3-monthly during FU, and yearly after 2 years during FU, at EOS
OS
Overall survival
Measured: Collected at a minimum at baseline, day 22 of Salvage therapy, last day of second cycle of consolidation therapy, 3-monthly during maintenance therapy, at EOT, 3-monthly during FU, and yearly after 2 years during FU, at EOS
CIR
Cumulative incidence of relapse
Measured: Collected at a minimum at baseline, day 22 of Salvage therapy, last day of second cycle of consolidation therapy, 3-monthly during maintenance therapy, at EOT, 3-monthly during FU, and yearly after 2 years during FU, at EOS
CID
Cumulative incidence of deaths
Measured: Collected at a minimum at baseline, day 22 of Salvage therapy, last day of second cycle of consolidation therapy, 3-monthly during maintenance therapy, at EOT, 3-monthly during FU, and yearly after 2 years during FU, at EOS
QoL
Quality of life
Measured: Collected at baseline, day 22 of Salvage therapy, last day of second cycle of consolidation therapy, 3-monthly during maintenance therapy, at EOT, 3-monthly during FU, and yearly after 2 years during FU, at EOS
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2019
- Study start17 Jul 2020
- Primary completion11 Sep 2022
- Study completion11 Sep 2022
Why it stopped: Study turned out no longer feasible
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AML According to WHO 2016 Classification (Except Acute Promyelocytic Leukemia) AND (Refractory to Induction Therapy OR Relapsed After First Line Treatment)Studies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Prof. Dr. Richard F Schlenk
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Prof. Dr. Richard F Schlenk, University Hospital Heidelberg
- Investigators
- Richard F. Schlenk, Prof. Dr., Principal investigator, University Hospital Heidelberg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03989713
- Sponsor's protocol ID
- HeLeNe-18-03-#545
- Acronym
- Q-HAM
- Status last verified
- Sep 2022
- First submitted
- 12 Apr 2019
- Last updated
- 15 Sep 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Jaramillo S, Le Cornet L, Kratzmann M, Krisam J, Gorner M, Hanel M, Rollig C, Wass M, Scholl S, Ringhoffer M, Reichart A, Steffen B, Kayser S, Mikesch JH, Schaefer-Eckart K, Schubert J, Geer T, Martin S, Kieser M, Sauer T, Kriegsmann K, Hundemer M, Serve H, Bornhauser M, Muller-Tidow C, Schlenk RF. Q-HAM: a multicenter upfront randomized phase II trial of quizartinib and high-dose Ara-C plus mitoxantrone in relapsed/refractory AML with FLT3-ITD. Trials. 2023 Sep 15;24(1):591. doi: 10.1186/s13063-023-07421-x.
PubMed 37715270
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Quizartinib and High-dose Ara-C Plus Mitoxantrone in Relapsed/Refractory AML With FLT3-ITD
- ClinicalTrials.gov ID
- NCT03989713
- Acronym / sponsor ID
- Q-HAM / HeLeNe-18-03-#545
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study turned out no longer feasible
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Prof. Dr. Richard F SchlenkUniversity, hospital or other
- Study start
- 17 Jul 2020 (actual)
- Primary completion
- 11 Sep 2022 (actual)
- Study completion
- 11 Sep 2022 (actual)
- First posted
- 18 Jun 2019 (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.
In this multicenter, upfront randomized phase II trial, all patients receive quizartinib in combination with HAM (high-dose cytarabine, mitoxantrone) during salvage therapy. Efficacy is assessed by comparison to historical controls based on the matched threshold crossing approach. During consolidation therapy (chemotherapy as well as allo-HCT) patients receive either prophylactic quizartinib therapy or MRD-triggered preemptive continuation therapy with quizartinib according to up-front randomization.
Detailed description
Acute myeloid leukemia (AML) is a clonal malignant disorder which is characterized by the expansion of leukemic blasts in the bone marrow and the peripheral blood, which goes along with a suppression of normal hematopoiesis including granulopoiesis, erythropoiesis and thrombocytopoiesis. The prognosis is largely determined by cytogenetic and molecular risk factors, age, performance status and antecedent myelodysplastic syndrome (MDS). With the exception of old and frail patients, most AML patients are eligible for intensive chemotherapy, which is given in curative intent consisting of induction and consolidation therapy. However, despite intensive therapy, the long-term outcome of AML patients remains poor, with less than 30% of patients achieving long lasting remission and even cure. This poor outcome is largely due to refractoriness to induction chemotherapy as well as relapses during and after completion of intensive induction and consolidation therapy. Regarding refractoriness, about 20-30% of AML patients under the age of 60 years and about 50% of older patients fail to attain complete remission (CR) following cytarabine plus anthracycline based standard induction therapy. In addition, patients having achieved CR are at a high risk of relapse, particularly within the first two years after completion of chemotherapy. Allogeneic hematopoietic cell transplantation (allo-HCT) is currently the only treatment strategy to offer the prospect of cure in relapsed/refractory (r/r)-AML; but outcome after allo-HCT is largely determined by the remission state before allo-HCT. With the aim to induce a CR before allo-HCT, salvage chemotherapy regimens are administered in r/r-AML. Typically, these salvage regimens are based on high dose cytarabine (HiDAC), which is frequently combined with either mitoxantrone (HAM regimen) or fludarabine plus idarubicin (idaFLA regimen). However, there is still no commonly accepted standard salvage regimen and overall CR rates remain low with less than one third of the patients achieving a CR. Apart from already known clinical unfavorable prognostic parameters in relapsed AML such as short first CR duration, older age and previous allo-HCT, FLT3-ITD has consistently been identified as an unfavorable molecular marker in both relapsed and refractory AML. Recently midostaurin has been approved by the FDA and EMA for the treatment of newly diagnosed AML with activating FLT3 mutations. But still roughly one quarter of patients, who received midostaurin, was refractory to induction therapy and relapse rate at 2 years excited 40%. Thus, new treatment options are urgently needed, particularly in r/r-AML with FLT3-ITD.
The oral second-generation bis-aryl urea tyrosine kinase inhibitor quizartinib is very specific for FLT3, has a high capacity for sustained FLT3 inhibition and an acceptable toxicity profile. Furthermore, single agent quizartinib doubled the response rate as compared to standard of care in a randomized study in r/r-AML. Although survival was also improved in this study the difference was only marginal.
In this protocol we evaluate the efficacy of quizartinib in combination with HAM (high-dose cytarabine, mitoxantrone) as compared to historical controls based on the matched threshold crossing approach followed by randomized prophylactic versus MRD-triggered continuation therapy with quizartinib including consolidation (chemotherapy as well as allo-HCT) and maintenance.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MRD-triggered arm | Experimental | Drug: MRD-triggered arm1. Salvage therapy: All patients are randomized upfront and receive one cycle Q-HAM salvage therapy. All patients achieving CR or CRi are allocated according to randomization to either MRD-triggered or prophylactic arm. (Duration: one cycle á 21 days followed by up to 3 weeks recovery period if needed, 22-42 days in total) 2. Consolidation therapy: Patients receive one cycle of HAM and are further allocated based on the MRD-results assessed by flow cytometry with a cut of level of 0.1%: if the MRD is negative they remain in the MRD-triggered arm, whereas MRD positive patients cross over to the prophylactic arm. (Up to 2 cycles. Duration: two cycles á 28 days each followed by up to two weeks recovery period if needed, 56-84 days in total.) 3. Observation: No treatment will be given in the MRD-triggered arm. (Duration: 48 weeks in total.) 4. Safety follow-up and observational follow-up |
| Prophylactic Arm | Experimental | Drug: Prophylactic Arm1. Salvage therapy: All patients are randomized upfront and receive one cycle Q-HAM salvage therapy. All patients achieving CR or CRi are allocated according to randomization to either MRD-triggered or prophylactic arm. (Duration: one cycle á 21 days followed by up to 3 weeks recovery period if needed, 22-42 days in total) 2. Consolidation therapy: Patients may receive up to two cycle of Q-HAM. (Up to 2 cycles. Duration: two cycles á 28 days each followed by up to two weeks recovery period if needed, 56-84 days in total.) 3. Maintenance therapy: Quizartinib will be given as single-agent therapy. The dose of quizartinib is aimed to be increased during maintenance therapy. (Up to 12 cycles. Duration: four times three cycles á 28 days, 48 weeks in total.) 4. Safety follow-up and observational follow-up |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Patients with acute myeloid leukemia according to the 2016 WHO classification (except acute promyelocytic leukemia) who are either A) refractory to induction therapy or B) relapsed after first line treatment including chemotherapy, autologous and/or allo-HCT (details below).
- Positive for FLT3-ITD (defined as a ratio of mutant to wild-type alleles of at least 0.05; measured within 2 weeks before inclusion)
- ECOG performance status ≤ 2. See appendix 18.1
- Adequate renal function defined as creatinine clearance >50 mL/min (calculated using the standard method for the institution)
- Discontinuation of prior AML treatment for at least A) 10 days for cytotoxic agents and B) 28 days for investigational drug treatment before the start of study treatment (except hydroxyurea or other treatment to control hyperleukocytosis)
Key exclusion criteria (26 listed)
- Acute promyelocytic leukemia (AML FAB M3 with t(15;17)(q22;q12) / PML-RARA)
- Patients with known CNS leukemia
- Isolated extramedullary manifestation of AML
- Patients with a "currently active" second malignancy other than non-melanoma skin cancer. Patients are not considered to have a "currently active" malignancy if they have completed therapy for more than one year and are considered by their physician to be at less than 30% risk of relapse within one year
- Hyperleukocytosis (leukocytes > 30,000/µl) at the time of study entry. 1)
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 |
|---|---|---|
| MRD-triggered arm1. Salvage therapy: Quizartinib: 40mg, p.o., Days: 4 - 21 Cytarabine: 18-60yrs: 3g/m² bid / >-60yrs: 1g/m² bid, i.v. 3h i.v. 3h, Days: 1,2,3; Mitoxantrone: 10mg, i.v. 30min: Days: 2,3; 2. Consolidation therapy: Cytarabine: 18-60yrs: 3g/m² bid, i.v. 3h / >-60yrs: 1g/m² bid, i.v. 3h, Days: 1,2,3; Mitoxantrone: 10mg, i.v. 30min, Days: 2,3 3. Observation therapy: No treatment | Drug | MRD-triggered arm |
| Prophylactic Arm1. Salvage therapy: Quizartinib: 40mg, p.o., Days: 4 - 21 Cytarabine: 18-60yrs: 3g/m² bid / >-60yrs: 1g/m² bid, i.v. 3h i.v. 3h, Days: 1,2,3; Mitoxantrone: 10mg, i.v. 30min: Days: 2,3; 2. Consolidation therapy: Quizartinib: 40mg, p.o., Days: 4 - 21 Cytarabine: 18-60yrs: 3g/m² bid, i.v. 3h / >-60yrs: 1g/m² bid, i.v. 3h, Days: 1,2,3; Mitoxantrone: 10mg, i.v. 30min, Days: 2,3; 3. Maintenance therapy: Quizartinib: Cycle 1, Days 1-15: 40mg, p.o. and Day 16-28: 60mg, p.o. | Drug | Prophylactic Arm |
Primary outcome
CRR
Time frame: Collected during the first MRD-analysis / after approximately 100 study days
Composite remission rate defined as the proportion of patients experiencing a CR (Complete remission)/CRi (Complete remission with incomplete hematological recovery rate) after salvage therapy.
6 secondary outcomes
EFS
Time frame: Collected at a minimum at baseline, day 22 of Salvage therapy, last day of second cycle of consolidation therapy, 3-monthly during maintenance therapy, at EOT, 3-monthly during FU, and yearly after 2 years during FU, at EOS
RFS
Time frame: Collected at a minimum at baseline, day 22 of Salvage therapy, last day of second cycle of consolidation therapy, 3-monthly during maintenance therapy, at EOT, 3-monthly during FU, and yearly after 2 years during FU, at EOS
OS
Time frame: Collected at a minimum at baseline, day 22 of Salvage therapy, last day of second cycle of consolidation therapy, 3-monthly during maintenance therapy, at EOT, 3-monthly during FU, and yearly after 2 years during FU, at EOS
CIR
Time frame: Collected at a minimum at baseline, day 22 of Salvage therapy, last day of second cycle of consolidation therapy, 3-monthly during maintenance therapy, at EOT, 3-monthly during FU, and yearly after 2 years during FU, at EOS
CID
Time frame: Collected at a minimum at baseline, day 22 of Salvage therapy, last day of second cycle of consolidation therapy, 3-monthly during maintenance therapy, at EOT, 3-monthly during FU, and yearly after 2 years during FU, at EOS
QoL
Time frame: Collected at baseline, day 22 of Salvage therapy, last day of second cycle of consolidation therapy, 3-monthly during maintenance therapy, at EOT, 3-monthly during FU, and yearly after 2 years during FU, at EOS
Results and safety
The study was stopped early (reason given: Study turned out no longer feasible). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2022.
- Derived from this study: PubMed 37715270Jaramillo S, Le Cornet L, Kratzmann M, Krisam J, Gorner M, Hanel M, Rollig C, Wass M, Scholl S, Ringhoffer M, Reichart A, Steffen B, Kayser S, Mikesch JH, Schaefer-Eckart K, Schubert J, Geer T, Martin S, Kieser M, Sauer T, Kriegsmann K, Hundemer M, Serve H, Bornhauser M, Muller-Tidow C, Schlenk RF. Q-HAM: a multicenter upfront randomized phase II trial of quizartinib and high-dose Ara-C plus mitoxantrone in relapsed/refractory AML with FLT3-ITD. Trials. 2023 Sep 15;24(1):591. doi: 10.1186/s13063-023-07421-x.
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. This study is not recruiting at the moment.
Richard F. Schlenk, Prof. Dr. principal investigator
University Hospital Heidelberg
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MRD-triggered arm and Prophylactic Arm in people with AML According to WHO 2016 Classification (Except Acute Promyelocytic Leukemia) AND (Refractory to Induction Therapy OR Relapsed After First Line Treatment), run by Prof. Dr. Richard F Schlenk at 1 site in Germany.
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 15 inclusion and 26 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: stopped early, as of the sponsor's last update on 15 Sep 2022. 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 Germany. 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 phase mean?
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?
The study was stopped early (reason given: Study turned out no longer feasible). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CRR (time frame: Collected during the first MRD-analysis / after approximately 100 study days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03989713, which also lists 1 linked publication.
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 15 Sep 2022.