Monitoring and Treatment of Relapsed Leukemia Following Allogeneic Hematopoietic Stem Cell Transplantation in Children

Phase 1

Terminated

• Conditions: Leukemia
• Interventions: Drug: Bortezomib; Drug: Pravastatin

• Registration Number: NCT02484261
• Lead Sponsor: Reuven Schore

Brief Summary

This study aims to monitor patients for relapse of the leukemia following allogeneic Hematopoietic Stem Cell Transplantation (HSCT) in order to identify patients early in relapse, with a low burden of disease, when interventions may be more successful by monitoring of peripheral blood lineage specific chimerism. Once disease has been confirmed, patients will initiate a novel combination of bortezomib and pravastatin.

Detailed Description

Patients will be enrolled on this study at the time of transplantation. Following HSCT, CD34+ chimerism in peripheral blood will be monitored in real time at scheduled intervals. If chimerism of CD34+ cells diminishes post-HSCT or clinical signs or symptoms of relapsed leukemia, relapse in bone marrow will be confirmed, after which immunosuppression will be withdrawn and treatment initiated with bortezomib and pravastatin. Patients will be monitored for disease response until 1 year post-HSCT or post-study therapy. Patients with confirmed relapse post-HSCT will also be eligible to enroll and receive novel combination.

Study Timeline

• Study Start: 2015-05
• Study First Submitted: 2015-06-24
• Study First Submitted QC: 2015-06-24
• Study First Posted: 2015-06-29
• Primary Completion: 2018-05-18
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-13
• Last Update Posted: 2023-03-15

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

Not provided

Exclusion Criteria

Patients meeting any of the following exclusion criteria are not to be treated on the study:

• Patient has greater than or equal to Grade 2 peripheral neuropathy
• Patient had myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening must be documented by the investigator as not medically relevant.
• Patient has hypersensitivity to bortezomib, boron, or mannitol.
• Female patients who are lactating or pregnant.
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
• Evidence of residual or relapse of another malignancy(other than the hematological malignancy which is the indication for stem cell transplant)at the time of transplant preparative regimen initiation
• Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of bortezomib/pravastatin and throughout the duration of therapy.
• Radiation therapy within 3 weeks before start of bortezomib/pravastatin. Enrollment of subjects who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Treatment phase	Bortezomib	Patients with confirmed disease will initiate therapy with bortezomib and pravastatin, a regimen that has efficacy in treatment of leukemia and graft-versus-host disease, while sparing healthy donor hematopoietic stem cells may improve the dismal survival of relapse post allogeneic transplant. Depending on response, patients may receive up to 13 cycles of therapy
Treatment phase	Pravastatin	Patients with confirmed disease will initiate therapy with bortezomib and pravastatin, a regimen that has efficacy in treatment of leukemia and graft-versus-host disease, while sparing healthy donor hematopoietic stem cells may improve the dismal survival of relapse post allogeneic transplant. Depending on response, patients may receive up to 13 cycles of therapy

Primary Outcome Measures

Name	Time	Method
Number of Participants with Adverse Events as a Measure of Safety and Tolerability	3 years	Tolerability of bortezomib and pravastatin in pediatric relapsed leukemia patients following allogeneic transplantation

Secondary Outcome Measures

Name	Time	Method
Number of relapses that are detected by CD34+ chimerism before clinical symptoms	3 years	The sensitivity of detection of recurrent acute leukemia in pediatric patients by peripheral blood CD34+ chimerism in pediatric patients following allogeneic HSCT

Trial Locations

Locations (1)

Children's National Medical Center; 🇺🇸 Washington, District of Columbia, United States