- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02484261
Monitoring and Treatment of Relapsed Leukemia Following Allogeneic Hematopoietic Stem Cell Transplantation in Children
March 13, 2023 updated by: Reuven Schore
Pilot Study to Evaluate the Tolerability of Velcade (Bortezomib) and Pravastatin for the Treatment of Relapsed Leukemia Following Allogeneic Hematopoietic Stem Cell Transplantation in Children
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.
Study Overview
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signs or symptoms of relapsed leukemia, relapse in bone marrow will be confirmed, after which immunosuppression will be withdrawn and treatment initiated with bortezomib and pravastatin.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 Type
Interventional
Enrollment (Actual)
10
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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District of Columbia
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Washington, District of Columbia, United States, 20010
- Children's National Medical Center
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
1 year to 21 years (Child, Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria to enter study:
- Voluntary written informed consent by patient or legal guardian (as appropriate) before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
Female patients who:
- Are postmenopausal for at least 1 year before the Screening visit, OR
- Are surgically sterile, OR
- If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 30 days after the last dose of study treatment, OR agree to completely abstain from heterosexual intercourse
OR Male patients, even if surgically sterilized (i.e., status postvasectomy), who:
- Agree to practice effective barrier contraception during the entire study treatment period and through 30 days after the last dose of study treatment, OR
Agree to completely abstain from heterosexual intercourse
- Lansky(if age <15)/Karnofsky (if age >16 yr) performance status > 50%
- Hepatic function: total bilirubin ≤ 2.5 mg/dl, and ALT/AST < or equal to 5 x the upper limit of normal
- Renal function: Creatinine clearance > 60 ml/min/1.73 m2 (as determined by 24 hour collection or nuclear (glomerular filtration rate) GFR or Cystatin C calculation)
- Cardiac function: LVEF > 50% or LVSF > 27%
- Pulmonary function tests: DLCO and FEV1 > 50% (if able to perform PFTs, if not able to perform PFTs SAO2> 94% on room air).
- Acute leukemia or Myelodysplastic syndrome (MDS)
Inclusion Criteria to initiate therapy with bortezomib and pravastatin
- Lansky performance status (if age < 15) /Karnofsky (if age >16 yr) performance status > 50%
- Hepatic function: total bilirubin ≤ 2.5 mg/dl, and ALT/AST < or equal to 5 x the upper limit of normal (ULN)
- Renal function: Cr < ULN for age
- Relapse of systemic disease documented by any of the following: morphology, flow cytometry, cytogenetics and/or FISH.
- Patient has a platelet count of more than 20,000/μL within 7 days before enrollment. Patients may be transfused prior to this evaluation but may not be platelet refractory at enrollment.
- Patient has an absolute neutrophil count of greater than 500 /μL within 7 days before enrollment.
- Patients with confirmed relapse post-HSCT who were not previously enrolled on monitoring portion of protocol, will also be eligible to enroll and receive novel combination if entry criteria met at time of relapse.
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 Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
No Intervention: Monitoring phase
Patients who have received a Stem cell transplant for Hematologic malignancies will be monitored for signs of relapse with blood tests for CD34+ chimerism.
Patients with signs of relapse will have bone marrow aspirate and/or other appropriate tests to confirm presence of relapse.
All patients who are confirmed to have relapsed and meet eligibility criteria to receive study drug will be eligible to receive treatment on the treatment arm.
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Experimental: Treatment phase
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
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1.3 mg/m2/dose subcutaneously (SQ) daily (total 4 doses) on Days 1, 4, 8 and 11 (+/- 1 day with at least 72 hours between doses) q3 weeks.
(For patients continuing to receive drug in cycles 6 or greater, at investigator discretion, the schedule may be changed to 1.3 mg/m2/dose SQ daily (total 3 doses) on Days 1, 8, and 15 (+/- 1 day with at least 72 hours between doses) every 4 weeks in an effort to decrease risk of peripheral neuropathy.)
Other Names:
10 mg for age < 8 years, 20 mg for age 8-<13 years, 40 mg for ages >14 years
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Time Frame: 3 years
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Tolerability of bortezomib and pravastatin in pediatric relapsed leukemia patients following allogeneic transplantation
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3 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of relapses that are detected by CD34+ chimerism before clinical symptoms
Time Frame: 3 years
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The sensitivity of detection of recurrent acute leukemia in pediatric patients by peripheral blood CD34+ chimerism in pediatric patients following allogeneic HSCT
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3 years
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Other Outcome Measures
Outcome Measure |
Time Frame |
---|---|
The number of patients who respond to bortezomib and pravastatin treatment for relapsed acute leukemia as defined by those that achieve complete response, partial response or stable disease
Time Frame: 3 years
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3 years
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Reuven Schore, MD, Children's National Research Institute
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
May 1, 2015
Primary Completion (Actual)
May 18, 2018
Study Registration Dates
First Submitted
June 24, 2015
First Submitted That Met QC Criteria
June 24, 2015
First Posted (Estimate)
June 29, 2015
Study Record Updates
Last Update Posted (Actual)
March 15, 2023
Last Update Submitted That Met QC Criteria
March 13, 2023
Last Verified
March 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- Pro00004062
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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