Leukemia
Conditions
Keywords
childhood leukemia, relapsed leukemia, Hematopoietic Stem Cell Transplantation
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signs or symptoms of relapsed leukemia, relapse in bone marrow will be confirmed, after which immunosuppression will be withdrawn and treatment initiated with bortezomib and pravastatin.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.
Interventions
DRUGBortezomib
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.)
DRUGPravastatin
10 mg for age \< 8 years, 20 mg for age 8-\<13 years, 40 mg for ages \>14 years
Sponsors
Millennium Pharmaceuticals, Inc.
Hyundai Hope On Wheels
Reuven Schore
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
22 Months to 21 Years
Healthy volunteers
No
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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care * Female patients who: * Are postmenopausal for at least 1 year before the Screening visit,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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Other
| 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 | 3 years |
Countries
United States
Outcome results
None listed