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Acute Myeloid Leukemia, in RelapsePhase 2SoraGVLNCT06532084

Sorafenib Relapase Prophylaxis After HCT With PTBCy Regimen

A Phase 2 study testing Sorafenib in people with Acute Myeloid Leukemia, in Relapse and Myelodysplastic Syndromes, run by St. Petersburg State Pavlov Medical University at 1 site in Russia.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

This is a single-center randomized open-label phase II clinical trial to compare relapse prophylaxis with sorafenib and observation after graft-versus-host disease prophylaxis with post-transplantation bendamustine and cyclophosphamide in high-risk myeloid malignancies. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Sorafenib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
88 participants
Where
1 siteRussia
Study dates
22 May 2024to May 2028
Phase
Phase 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 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must undergo allogeneic hematopoietic stem cell transplantation with post-transplantation bendamustine AND cyclophosphamide from any donor.
  • Patients must have high-risk myeloid malignancy as an indication for transplantation defined as:
  • acute myeloid leukemia not in hematological remission prior to transplantation,
  • ≥ 3 remission of acute myeloid leukemia,
  • any myeloid malignancy with bi-allelic tp53 mutation,
  • any myeloid malignancy with complex karyotype,
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  • therapy-related myeloid malignancy not in MRD-negative response
  • myelodysplastic syndrome with very high IPSS-R risk
  • any myeloid malignancy with monosomal or t(3;3) karyotype,
  • any myeloid malignancy with ASXL1, bi-allelic tp53 or RUNX1 mutation, EVI1 overexpression
  • MDS/NPM unclassified not in hematologic remission.
  • Documented hematological remission in the bone marrow at the time of inclusion post-engraftment, measurable residual disease is allowed
  • First 100 days after allogeneic hematopoietic stem cell transplantation

Who cannot join

  • successfully treated relapse between transplantation and enrollment
  • use of any other planned method for prophylaxis of relapse besides sorafenib
  • donor lymphocyte infusion prior to randomization
  • Second malignancy not in complete remission within 6 months prior to randomization
  • Moderate or severe cardiac disease: ejection fraction <50%, unstable angina, stable angina NYHA class III or IV, chronic heart failure NYHA class III or IV, Lawn grade V arrhythmia, myocardial infarction within 3 months before inclusion
  • Stroke within 3 months of inclusion, unless related to the underlying malignancy
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  • Severe decrease in pulmonary function: FEV1 <50% or DLCO<50% of predicted or respiratory distress or need for oxygen support;
  • Severe organ dysfunction: AST or ALT >10 upper normal limits, bilirubin >2 upper normal limits, creatinine >2 upper normal limits
  • Creatinine clearance < 30 mL/min
  • Uncontrolled bacterial or fungal infection at the time of enrollment defined by CRP> 70 mg/L
  • Requirement for vasopressor support at the time of enrollment
  • Requirement for positive-pressure oxygen at the time of enrollment
  • Karnofsky index <30%
  • Pregnancy
  • Somatic or psychiatric disorder making the patient unable to sign informed consent

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

IVAN S MOISEEV contact

+78123386265

moisiv@mail.ru

Irina V Bykova contact

+78123386617

bmt-director@1spbgmu.ru

Russia1 site, 1 recruiting

  • RM Gorbacheva Research Institute

    Saint Petersburg, 197022

    Ivan Moiseev, +79217961951, moisiv@mail.ru

    Alexandr Kulagin, +78123386265, bmt-director@1spbgmu.ru

    Recruiting

Other trials in Russia

About this study

Official title: Randomized Trial of Sorafenib Prophylaxis After Allogeneic Hematopoietic Stem Cell Transplantation With Post-transplantation Bendamustine and Cyclophosphamide

This is a single-center randomized open-label phase II clinical trial to compare relapse prophylaxis with sorafenib and observation after graft-versus-host disease prophylaxis with post-transplantation bendamustine and cyclophosphamide in high-risk myeloid malignancies. This is an intention to treat study, where randomization is performed at first documentation of CR after engraftment.

Read the detailed description

Allogeneic hematopoietic stem cell transplantation (HCT) results steadily improve due to reduction of NRM. Standard risk patients now have the risk of HCT below 10% after matched donor transplantation. Nonetheless, there is limited improvement in CIR over time. Especially novel strategies to reduce relapse are needed for high-risk myeloid malignancies where standard HCT approaches result in relatively unfavorable outcomes. Among high-risk malignancies are refractory AML without hematological remission for HCT. In this group EFS rarely exceeds 15%. Some improvement in refractory AML was reported with intensified sequential conditioning regimens, but there use is limited to young and fit patients who comprise only around 20-30% of all refractory AML population. Also it was demonstrated that AML patients beyond CR2 have significantly worse prognosis than CR1 and CR2 patients. It is reported that long-term EFS in this group of patients is around 30%. The next adverse group of HCT recipients are patients with high-risk somatic mutations. It is reported in several studies that EFS in tp53-mutant AML even allografted in CR is 0%. Another adverse mutation is ASXL1, where also 0-10% EFS was demonstrated in large cohorts of patients. For therapy related myeloid malignancies it was also demonstrated that the CIR is higher and this group patients have even in CR have 30% EFS. Complex karyotype and monosomal karytope, involvement of chromosome 3 with EVI1 gene, which are common in this patients group, further exacerbate prognosis. Very high risk MDS was also reported to have dismal prognosis after allogeneic HCT. All these adverse groups were included in the study.

PTBCy GVHD prophylaxis provides augmented GVL and better disease control in high-risk myeloid malignancies, but GVL effect fades over time. While median relapse rate is significantly prolonged to 8 months against the previously reported in the literature 2-3 months, the relapse rate with long term follow up remains high. Thus this longer time to relapse gives enough time to initiate sorafenib prophylaxis which was shown to be one of the most promising agents for relapse prophylaxis. Given its immune modulatory properties the study hypothesis is that sorafenib with PTBCy GVHD prohylaxis will further augment GVL and facilitate better disease control.

Being tested
Sorafenib
Keywords
post-transplantation cyclophosphamide; post-transplantation bendamustine; acute myeloid leukemia; myelodysplastic syndrome; refractory; sorafenib
Medical subject headings
Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Myeloproliferative Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SorafenibDrug

    Sorafenib 200 mg bid for 168 days starting in the time fram between engraftment with neutrophils > 1.0 x 10^9/L, white blood cells> 1.5 x 10^9/L, platelets> 1.5 x 10^9/L and day+100 after allogeneic hematopoietic cell trnaplantation

Study groups in NCT06532084
Study groupRoleWhat they receive
Sorafenib prophylaxisExperimentalSorafenib 200 mg bid for 168 days starting before day+100 after HCT
Receives: Drug: Sorafenib
ObservationNo interventionUsual care

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Event-free survival

    Kaplan-Meier estimate of either relapse or secondary graft failure or death from all causes

    Measured: 2 years

Secondary outcomes (9)

  1. Overall survival

    Kaplan-Meier estimate of death from all causes

    Measured: 2 years

  2. Cumulative incidence of primary and secondary graft failure

    Cumulative secondary graft failure, competing risk is death and relapse

    Measured: 365 days

  3. Incidence of HCT-associated adverse events

    Toxicity assessment is based on presence of NCI CTC AE 5.0 event grades 3-5. Veno-occlusive disease incidence and severity assessment is based on EBMT criteria 2020. Transplant-associated microangiopathy incidence assessment is based on Harmonization criteria. All toxicity measurements will be aggregated as severity scores.

    Measured: 180 days

  4. Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence

    proportion of patients, requiring systemic treatment for bacterial, viral and fungal diseases

    Measured: 180 days

  5. Cumulative incidence of acute GVHD grade II-IV

    125 days

    Measured: Cumulative incidence of patients with acute GVHD II-IV grade, competing risk is death, relapse and graft failure

  6. Cumulative incidence of moderate and severe chronic GVHD

    Cumulative incidence of patients with moderate and severe chronic GVHD according to NIH 2015 criteria, competing risk is death, relapse and primary graft failure

    Measured: 2 years

  7. Non-relapse mortality analysis

    Cumulative incidence of patients with mortality without hematological relapse of malignancy

    Measured: 2 years

  8. GVHD-relapse-free survival analysis

    Kaplan-Meier estimate of death, acute GVHD grade III-IV, severe chronic GVHD or relapse

    Measured: 2 years

  9. Cumulative incidence of relapse

    Cumulative incidence of patients with relapse, competing risk is non-relapse mortality

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Aug 2024
  2. Study start22 May 2024
  3. Primary completionMay 2027 (estimated)
  4. Study completionMay 2028 (estimated)

Resources

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
Parallel groups
Model description
In total 88 patients will be included in the study. After inclusion into the study patients will be randomized in 1:1 proportion in two arms (44 patients per arm): treatment with sorafenib or observation. Patients will be followed up for two years. The strata is a type of donor.
Masking
None (open label)
Enrolment
88 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06532084
Sponsor's protocol ID
19/24-n
Acronym
SoraGVL
Status last verified
Jul 2024
First submitted
29 Jul 2024
Last updated
1 Aug 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Upon written study proposal according to Pavlov University LEC SOPs.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Sorafenib in people with Acute Myeloid Leukemia, in Relapse and Myelodysplastic Syndromes, run by St. Petersburg State Pavlov Medical University 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 13 inclusion and 15 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: looking for participants now, as of the sponsor's last update on 1 Aug 2024. 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 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 IVAN S MOISEEV (+78123386265, moisiv@mail.ru), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Event-free survival (time frame: 2 years). 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 NCT06532084.

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 1 Aug 2024.

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