Sorafenib Relapase Prophylaxis After HCT With PTBCy Regimen

NCT06532084 | Recruiting Phase 2 DMC

• 1 other identifier: 19/24-n
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 1

Brief 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. This is an intention to treat study, where randomization is performed at first documentation of CR after engraftment.

Conditions

Acute Myeloid Leukemia, in Relapse; Myelodysplastic Syndromes; Chronic Myeloid Leukemia; Myeloproliferative Neoplasm

Keywords

post-transplantation cyclophosphamide; post-transplantation bendamustine; acute myeloid leukemia; myelodysplastic syndrome; refractory; sorafenib

Outcome Measures

Primary Outcomes (1)

• Event-free survival

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

  2 years

Secondary Outcomes (9)

• Overall survival

  2 years

• Cumulative incidence of primary and secondary graft failure

  365 days

• Incidence of HCT-associated adverse events

  180 days

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

  180 days

• Cumulative incidence of acute GVHD grade II-IV

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

Study Arms (2)

Sorafenib prophylaxis

EXPERIMENTAL

Sorafenib 200 mg bid for 168 days starting before day+100 after HCT

Drug: Sorafenib

Observation

NO INTERVENTION

Usual care

Interventions

Sorafenib DRUG

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

Sorafenib prophylaxis

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• First 100 days after allogeneic hematopoietic stem cell transplantation

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• St. Petersburg State Pavlov Medical University: lead

Study Sites (1)

RM Gorbacheva Research Institute

Saint Petersburg, 197022, Russia

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Myeloproliferative Disorders

Interventions

Sorafenib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Central Study Contacts

IVAN S MOISEEV

CONTACT

+78123386265; moisiv@mail.ru

Irina V Bykova

CONTACT

+78123386617; bmt-director@1spbgmu.ru

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice-director of RM Gorbacheva Research Institute

Model Details: 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.

Study Record Dates

• First Submitted: July 29, 2024
• First Posted: August 1, 2024
• Study Start: May 22, 2024
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2028
• Last Updated: August 1, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

RU (1)