Using Sorafenib to Prevent Relapse After Stem Cell Transplantation

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

This study is testing if the drug sorafenib can help prevent relapse in patients with high-risk blood cancers after they receive a stem cell transplant.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 88 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: St. Petersburg State Pavlov Medical University (other)
• Drugs / interventions: cyclophosphamide
• Locations: 1 site (Saint Petersburg)
• Trial ID: NCT06532084 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of sorafenib as a relapse prophylaxis in patients with high-risk myeloid malignancies following allogeneic hematopoietic stem cell transplantation (HCT) using a post-transplantation bendamustine and cyclophosphamide regimen. It is a single-center, randomized, open-label phase II trial that compares the outcomes of patients receiving sorafenib against those under observation after achieving complete remission post-engraftment. The study aims to address the high relapse rates in patients with refractory acute myeloid leukemia and other high-risk myeloid conditions, where traditional HCT approaches have shown limited success. Participants will be monitored for relapse rates and overall survival to determine the efficacy of the intervention.

Who should consider this trial

Good fit: Ideal candidates include patients with high-risk myeloid malignancies undergoing allogeneic HCT who are not in hematological remission prior to transplantation.

Not a fit: Patients with low-risk myeloid malignancies or those who are in complete remission prior to transplantation may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly reduce relapse rates and improve survival outcomes for patients with high-risk myeloid malignancies.

How similar studies have performed: While there have been studies exploring relapse prophylaxis in similar contexts, the specific use of sorafenib in this high-risk population represents a novel approach.

Eligibility criteria

Inclusion Criteria:

* 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,
  * 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

Exclusion Criteria:

* 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
* 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

Where this trial is running

Saint Petersburg

• RM Gorbacheva Research Institute — Saint Petersburg, Russia (RECRUITING)

Study contacts

• Study coordinator: IVAN S MOISEEV

Conditions: Acute Myeloid Leukemia, in Relapse, Myelodysplastic Syndromes, Chronic Myeloid Leukemia, Myeloproliferative Neoplasm, post-transplantation cyclophosphamide, post-transplantation bendamustine, acute myeloid leukemia, myelodysplastic syndrome