Refractory Acute Myeloid LeukemiaPhase 3NCT06418776
IMPACT-AML: Randomized Pragmatic Clinical Trial for Relapsed or Refractory AML
A Phase 3 study testing Intensive therapy and Low intensity therapy in people with Refractory Acute Myeloid Leukemia and Early Relapses of Acute Myeloid Leukemia, run by National Research Center for Hematology, Russia at 1 site in Russia.
Trial summary
The primary objective is to evaluate the efficacy and toxicity of high versus low intensity therapy options in patients with refractory forms and early relapses of acute myeloid leukemia (R/R AML) who are scheduled for allogeneic hematopoietic stem cell transplantation (alloHSCT). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Refractory Acute Myeloid Leukemia, Early Relapses of Acute Myeloid Leukemia
- What is being tested?
- Intensive therapy and Low intensity therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 198 participants
- Where
- 1 siteRussia
- Study dates
- 1 Apr 2024to May 2029
- Phase
- Phase 3
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years;
- Primary refractory AML;
- Early relapsed AML;
- A signed informed consent to participate in the study.
Who cannot join
- Late relapsed AML;
- Isolated extramedullary relapse;
- MRD relapse without development of bone marrow relapse of AML;
- Acute promyelocytic leukemia;
- Previous refractoriness or loss of response during ongoing venetoclax therapy;
- Previous alloHSCT;
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- Pregnancy and/or lactation period;
- Refusal of patients with preserved reproductive potential to use highly effective methods of contraception during the period of participation in the study;
- Lack of signed informed consent to participate in the study;
- Failure of the subject to follow the study protocol;
- Participation in any other clinical trial;
- Uncontrolled infectious complications;
- ECOG ≥ 3;
- History of other malignancies within the past 3 years, excluding squamous cell and basal cell skin cancers, carcinoma in situ of the cervix, breast, or other non-invasive malignancies, which, in the opinion of the investigator, are considered adequately treated and have a minimal risk of recurrence within 3 years;
- Chronic kidney disease with GFR ≤ 30 ml/min/1.73 m2 (according to the CKD-EPI Creatinine Equation);
- Severe cardiac pathology:
- uncontrolled arterial hypertension;
- stable angina III-IV functional classes;
- unstable angina and/or myocardial infarction less than 6 months before inclusion in the study;
- heart failure stages IIb-III, NYHA functional classes III-IV
- uncontrolled cardiac rhythm disturbances (≥ 2 grade CTCAE 5.0) or clinically significant ECG abnormalities.
- Cirrhosis classes B-C according to the Child-Pugh classification
- Increased liver function tests above the following values:
- Total bilirubin > 1,5 above the normal range;
- AST, ALT > 10 above the normal range.
- Major surgical interventions underwent less than 14 days before inclusion in the study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Russia1 site, 1 recruiting
- Recruiting
National Research Center for Hematology
Moscow, 125167
Elena Parovichnikova, MD, +74956122361, director@blood.ru
Anastasia Kashlakova, MD, +74956124592, kashlakova.a@blood.ru
About this study
Official title: A Prospective Multicenter Randomized Clinical Trial on the Treatment of Patients With Refractory or Early Relapses of Acute Myeloid Leukemia
The primary objective is to evaluate the efficacy and toxicity of high versus low intensity therapy options in patients with refractory forms and early relapses of acute myeloid leukemia (R/R AML) who are scheduled for allogeneic hematopoietic stem cell transplantation (alloHSCT).
- Being tested
- Intensive therapy, Low intensity therapy
- Keywords
- Acute myeloid leukemia, Relapse of AML, Refractory AML, Allogeneic Stem Cell Transplantation
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intensive therapyOther
Intensive chemotherapy courses (MEC, FLAG, FLAG-Ida, FLAG-Mito)
Low intensity therapyOther
Low intensity therapy (Aza+Ven, Dac+Ven, LDARA-C+Ven)
| Study group | Role | What they receive |
|---|---|---|
| Intensive arm | Active comparator | Fit patients who could potentially undergo courses of intensive chemotherapy and are randomized to intensive chemotherapy courses Receives: Other: Intensive therapy |
| Low-intensive arm | Active comparator | Fit patients who could potentially undergo courses of intensive chemotherapy and are randomized to low intensity courses Receives: Other: Low intensity therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event-free survival of patients with R/R AML depending on the use of high or low intensity therapy exposure before alloHSCT
Evaluation method: Kaplan-Meier curves and log-rank test, censored for transplantation
Measured: 2 years
Secondary outcomes (9)
Probability of achieving CR in patients with R/R AML, depending on the use of high or low intensity treatment regimens
Assessment method: Chi-square test
Measured: 3 months
Probability of achieving a response (CR, CR with incomplete hematological recovery, morphologic leukemia- free state, partial remission) in patients with R/R AML, depending on the use of high or low intensity treatment regimens
Assessment method: Chi-square test
Measured: 3 months
Cumulative incidence of alloHSCT in patients with R/R AML, depending on the use of high or low intensity treatment regimens
Evaluation method: cumulative frequency curves and Gray's test
Measured: 2 years
Toxicity of high versus low intensity regimens
Evaluation method: Chi-square test, parametric/nonparametric tests for means
Variables to be evaluated:
- Maximum degree and duration of neutropenia and/or thrombocytopenia;
- Development of uncontrolled/life-threatening infectious complications;
- Development of life-threatening hemorrhagic complications;
- Development of severe organ failure.
Measured: 3 months
OS over the entire duration of the study, including follow-up after alloHSCT
Evaluation method: Kaplan-Meier curves and log-rank test
Measured: 2 years
RFS in patients with R/R AML when achieving remission before alloHSCT, depending on the use of high or low intensity treatment regimens
Evaluation method: Kaplan-Meier curves and log-rank test
Measured: 2 years
Relapse incidence in patients with R/R AML when achieving remission before performing alloHSCT, depending on the use of high or low intensity treatment regimens
Evaluation method: cumulative frequency curves and Gray's test
Measured: 2 years
EFS of patients with R/R AML depending on the use of high or low intensity regimens, regardless of alloHSCT
Evaluation method: Farington-Manning test, not censored for transplantation
Measured: 2 years
Statistics on discontinued participation in the protocol and premature withdrawal from the study
Assessment method: Chi-square test
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2024
- Study start1 Apr 2024
- Primary completionApr 2027 (estimated)
- Study completionMay 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Refractory Acute Myeloid LeukemiaStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients who could potentially undergo courses of intensive chemotherapy ("fit") are randomisedrandomized into two arms: * Arm 1 - intensive chemotherapy courses (MEC, FLAG, FLAG-Ida, FLAG-Mito) * Arm 2 - low intensity therapy (Aza/Dac/LDARA-C + Ven) Randomization determines the intensity of the program, but not the specific therapeutic regimen. The treatment regimen is selected by the investigators based on accepted clinical practice, the availability of appropriate drugs at the participating centers, etc., after randomization. If a patient has FLT3 gene mutations, one of the available kinase inhibitors must be added to therapy: midostaurin, gilteritinib, sorafenib. If remission of the AML has been achieved, patients in both groups undergo alloHSCT as soon as possible.
- Masking
- None (open label)
- Enrolment
- 198 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Research Center for Hematology, Russia
- Sponsor type
- Research network
- Collaborators
- St. Petersburg State Pavlov Medical University, Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health
- Responsible party
- Principal investigator, Elena N.Parovichnikova, National Research Center for Hematology, Russia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06418776
- Sponsor's protocol ID
- IMPACT-AML
- Status last verified
- May 2024
- First submitted
- 9 Apr 2024
- Last updated
- 17 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Each center participating in the study includes patients and fills CRF forms separately.