Refractory Acute Myeloid LeukemiaPhase 3NCT04000698
Personalized Targeted Preparative Regimen Before T-depleted Allogeneic HSCT in Children With Chemoresistent Acute Leukemias
A Phase 3 study testing Preparative regimen in people with Refractory Acute Myeloid Leukemia and Refractory Acute Lymphoblastic Leukemia, run by Federal Research Institute of Pediatric Hematology, Oncology and Immunology at 1 site in Russia.
Trial summary
The purpose of this study is to evaluate the safety and efficiency of personalized targeted therapy in combination with high-dose chemotherapy as part of a preparative regimen before T-depleted allogeneic hematopoietic stem cell transplantation in children with chemoresistant acute leukemias Read more about this study
- Who is it for?
- Ages Up to 25 years
- Conditions the study is for
- Refractory Acute Myeloid Leukemia, Refractory Acute Lymphoblastic Leukemia
- What is being tested?
- Preparative regimen
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteRussia
- Study dates
- 15 Oct 2019to Dec 2022
- Phase
- Phase 3
- 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 Up to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Ability to give informed consent (for patients > 14 years old). For subjects < 18 years old their legal guardian must give informed consent
- Disease stage
- Acute myeloid leukemia (AML), relapsed or refractory, failure to achieve hematologic remission after at least to courses of intensive chemotherapy, including at least one course with high-dose AraC and fludarabine
- Acute lymphoblastic leukemia (ALL), relapsed or refractory, failure to achieve hematologic remission after at least two high-dose therapy blocks
- Patient eligible for current hematopoietic stem cell transplantation protocol
- The BCL-2 expression must be detected on greater than 30% of tumor cells (AML and ALL) by flow cytometry
Show all 12Show fewer
- CD38 expression must be detected on greater than 30% of tumor cells (AML and ALL) by flow cytometry
- CD184
- Patients must have measurable or evaluable disease at the time of enrollment, which may include any evidence of disease including minimal residual disease detected by flow cytometry, cytogenetics, or polymerase chain reaction (PCR) analysis.
- Patient Clinical Performance Status: Karnofsky >50% or Lansky >50%
- Patient Life Expectancy >12 weeks
- Patients who agree to long-term follow up for up to 5 years
Who cannot join
- Age >25 years
- Patients with uncontrolled infections
- Clearance of creatinine < 70 ml/min
- Cardiac ejection fraction < 40%
- Patients who can perform pulmonary function tests will be excluded if they have a diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin) of < 50% predicted; patients who are unable to perform pulmonary function tests will be excluded if the oxygen (O2) saturation is < 92% on room air
- Patients who have liver function test (LFTs) (including total bilirubin, aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) >= twice the upper limit of normal
- Karnofsky/Lansky Scale <70%
Trial locations and contacts
1 site in 1 country.
Russia1 site, 1 recruiting
- Recruiting
Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology
Moscow, 117997
Zhanna Shekhovtsova, MD, 4956647078 ext. 7538, zhanna.shekhovtsova@fccho-moscow.ru
Eugene Pashanov, PhD, +79262205578, e.pashanov@gmail.com
About this study
Official title: A Phase I-II Pilot Clinical Trial of Safety and Efficacy of Personalized Targeted Preparative Regimen With Allogeneic TcRαβ/CD19-depleted Hematopoietic Stem Cell Transplantation and Posttransplant Donor T- Cells Infusion in Children With Chemoresistаnt Acute Leukemia.
The purpose of this study is to evaluate the safety and efficiency of personalized targeted therapy in combination with high-dose chemotherapy as part of a preparative regimen before T-depleted allogeneic hematopoietic stem cell transplantation in children with chemoresistant acute leukemias
Read the detailed description
The outcome of hematopoietic stem cell transplantation (HSCT) in a cohort of children with chemorefractory leukemia is poor. The incidence of relapse exceeds 50% and survival varies from 10 to 40%. Additional attempts at remission induction with various combinations of chemotherapy are unlikely to improve the outcome and will contribute to toxicity.
The hypothesis of the study is that personalized targeted therapy combined with high-dose chemotherapy may improve the outcome of allogeneic HSCT in a cohort of pediatric patients with refractory leukemia.
Bcl-2, CD38, CD184 were chosen as potential targets due to frequent expression in pediatric acute leukemias, availability of marketed targeted therapies venetoclax, daratumumab and prelixafor, and expected non-overlapping toxicity profile of these agents and the conditioning regimen.
- Being tested
- Preparative regimen
- Medical subject headings
- Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Preparative regimenDrug
Preparative chemotherapy before allogeneic HSCT
- Fludarabin
- Cytarabine
- Venetoclax
- Daratumomab
- Vecanoid Condition
- treosulfan
- fludarabine
- thiophosphomide
- Venetoclax
- Plerixafor GVHD prophylaxis
- abatacept
- tocilizumab
- rituximab
- HSCT from the haploidentical donor, ex vivo depleted of alpha/beta T lymphocytes
| Study group | Role | What they receive |
|---|---|---|
| intervention/treatment | Experimental | Preparative chemotherapy before allogeneic HSCT
* Fludarabin
* Cytarabine
* Venetoclax
* Daratumomab
* Vecanoid
* treosulfan
* fludarabine
* thiophosphomide
* Venetoclax
* Plerixafor
* abatacept
* tocilizumab
* rituximab
* HSCT from the haploidentical donor, ex vivo depleted of alpha/beta T lymphocytes Receives: Drug: Preparative regimen |
What is being measured
The primary outcome is the main question the study is designed to answer.
cumulative incidence of neutrophil and platelets engraftment at day +30 after HSCT
Measured: 30 days after HSCT
Overall response rate
Proportion of patients with hematologic remission at time points
Measured: 30 days after HSCT
Partial response rate
Proportion of patients with MRD negativity at time points
Measured: 30 days after HSCT
Rate of toxicity stage > 3 according to CTCAE 5.0
Proportion of patients with allergic/ anaphylaxis reaction toxicity stage > 3 according to CTCAE 5.0
Measured: 40 days after first drug administration
cumulative incidence of transplant-related mortality
Measured: 100 days after HSCT
Secondary outcomes (6)
Rate of expression of target molecule on blast cells
Proportion of patients with target molecule on blast cells: CD38 and/or CD 184 and/or Bcl2
Measured: 1 week before first drug administration
cumulative incidence of acute GVHD grade II-IV
Measured: 120 days after HSCT
cumulative incidence of chronic GvHD
Measured: 1 year after HSCT
Rate of immune recovery at day 30
Proportion of patients with early immune recovery: T-cell, NK- cell, B-cell >determined numbers
Measured: 30
overall survival
Measured: 1 year after HSCT
event-free survival
Measured: 1 year after HSCT
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2019
- Study start15 Oct 2019
- Primary completionJul 2022 (estimated)
- Study completionDec 2022 (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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Federal Research Institute of Pediatric Hematology, Oncology and Immunology
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04000698
- Sponsor's protocol ID
- NCPHOI-2018-08
- Status last verified
- Nov 2020
- First submitted
- 25 Jun 2019
- Last updated
- 20 Nov 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I-II Pilot Clinical Trial of Safety and Efficacy of Personalized Targeted Preparative Regimen With Allogeneic TcRαβ/CD19-depleted Hematopoietic Stem Cell Transplantation and Posttransplant Donor T- Cells Infusion in Children With Chemoresistаnt Acute Leukemia.
- ClinicalTrials.gov ID
- NCT04000698
- Acronym / sponsor ID
- NCPHOI-2018-08
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Federal Research Institute of Pediatric Hematology, Oncology and ImmunologyUniversity, hospital or other
- Study start
- 15 Oct 2019 (actual)
- Primary completion
- Jul 2022 (estimated)
- Study completion
- Dec 2022 (estimated)
- First posted
- 27 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.
The purpose of this study is to evaluate the safety and efficiency of personalized targeted therapy in combination with high-dose chemotherapy as part of a preparative regimen before T-depleted allogeneic hematopoietic stem cell transplantation in children with chemoresistant acute leukemias
Detailed description
The outcome of hematopoietic stem cell transplantation (HSCT) in a cohort of children with chemorefractory leukemia is poor. The incidence of relapse exceeds 50% and survival varies from 10 to 40%. Additional attempts at remission induction with various combinations of chemotherapy are unlikely to improve the outcome and will contribute to toxicity.
The hypothesis of the study is that personalized targeted therapy combined with high-dose chemotherapy may improve the outcome of allogeneic HSCT in a cohort of pediatric patients with refractory leukemia.
Bcl-2, CD38, CD184 were chosen as potential targets due to frequent expression in pediatric acute leukemias, availability of marketed targeted therapies venetoclax, daratumumab and prelixafor, and expected non-overlapping toxicity profile of these agents and the conditioning regimen.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| intervention/treatment | Experimental | Drug: Preparative regimenPreparative chemotherapy before allogeneic HSCT * Fludarabin * Cytarabine * Venetoclax * Daratumomab * Vecanoid * treosulfan * fludarabine * thiophosphomide * Venetoclax * Plerixafor * abatacept * tocilizumab * rituximab * HSCT from the haploidentical donor, ex vivo depleted of alpha/beta T lymphocytes |
Who may qualify
- Ages
- Up to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (12 listed)
- Ability to give informed consent (for patients > 14 years old). For subjects < 18 years old their legal guardian must give informed consent
- Disease stage
- Patient eligible for current hematopoietic stem cell transplantation protocol
- The BCL-2 expression must be detected on greater than 30% of tumor cells (AML and ALL) by flow cytometry
- CD38 expression must be detected on greater than 30% of tumor cells (AML and ALL) by flow cytometry
Key exclusion criteria (7 listed)
- Age >25 years
- Patients with uncontrolled infections
- Clearance of creatinine < 70 ml/min
- Cardiac ejection fraction < 40%
- Patients who can perform pulmonary function tests will be excluded if they have a diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin) of < 50% predicted; patients who are unable to perform pulmonary function tests will be excluded if the oxygen (O2) saturation is < 92% on room air
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 |
|---|---|---|
| Preparative regimenPreparative chemotherapy before allogeneic HSCT * Fludarabin * Cytarabine * Venetoclax * Daratumomab * Vecanoid Condition * treosulfan * fludarabine * thiophosphomide * Venetoclax * Plerixafor GVHD prophylaxis * abatacept * tocilizumab * rituximab * HSCT from the haploidentical donor, ex vivo depleted of alpha/beta T lymphocytes | Drug | intervention/treatment |
Primary outcome
cumulative incidence of neutrophil and platelets engraftment at day +30 after HSCT
Time frame: 30 days after HSCT
Overall response rate
Time frame: 30 days after HSCT
Proportion of patients with hematologic remission at time points
Partial response rate
Time frame: 30 days after HSCT
Proportion of patients with MRD negativity at time points
Rate of toxicity stage > 3 according to CTCAE 5.0
Time frame: 40 days after first drug administration
Proportion of patients with allergic/ anaphylaxis reaction toxicity stage > 3 according to CTCAE 5.0
cumulative incidence of transplant-related mortality
Time frame: 100 days after HSCT
6 secondary outcomes
Rate of expression of target molecule on blast cells
Time frame: 1 week before first drug administration
cumulative incidence of acute GVHD grade II-IV
Time frame: 120 days after HSCT
cumulative incidence of chronic GvHD
Time frame: 1 year after HSCT
Rate of immune recovery at day 30
Time frame: 30
overall survival
Time frame: 1 year after HSCT
event-free survival
Time frame: 1 year after HSCT
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2020.
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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. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Preparative regimen in people with Refractory Acute Myeloid Leukemia and Refractory Acute Lymphoblastic Leukemia, run by Federal Research Institute of Pediatric Hematology, Oncology and Immunology at 1 site in Russia.
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 12 inclusion and 7 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: status not confirmed, as of the sponsor's last update on 20 Nov 2020. 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 Russia. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Larisa Shelikhova (84956647078, larisa.shelikhova@fccho-moscow.ru), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
cumulative incidence of neutrophil and platelets engraftment at day +30 after HSCT (time frame: 30 days after HSCT). The study lists 5 primary outcomes in all. 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 20 Nov 2020.