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

NCT02484261 | Terminated Phase 1 DMC

• 1 other identifier: Pro00004062
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Leukemia

Keywords

childhood leukemia; relapsed leukemia; Hematopoietic Stem Cell Transplantation

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Adverse Events as a Measure of Safety and Tolerability

  Tolerability of bortezomib and pravastatin in pediatric relapsed leukemia patients following allogeneic transplantation

  3 years

Secondary Outcomes (1)

• Number of relapses that are detected by CD34+ chimerism before clinical symptoms

  3 years

Other Outcomes (1)

• 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

Study Arms (2)

Monitoring phase

NO INTERVENTION

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.

Treatment phase

EXPERIMENTAL

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

Drug: Bortezomib; Drug: Pravastatin

Interventions

Bortezomib DRUG

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.)

Also known as: Velcade

Treatment phase

Pravastatin DRUG

10 mg for age \< 8 years, 20 mg for age 8-\<13 years, 40 mg for ages \>14 years

Treatment phase

Eligibility Criteria

• Age: 22 Months - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)
• Lansky performance status (if age \< 15) /Karnofsky (if age \>16 yr) performance status \> 50%

You may not qualify if:

• 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.

Sponsors & Collaborators

• Reuven Schore: lead
• Millennium Pharmaceuticals, Inc.: collaborator
• Hyundai Hope On Wheels: collaborator

Study Sites (1)

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

MeSH Terms

Conditions

Leukemia

Interventions

Bortezomib; Pravastatin

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Officials

• Reuven Schore, MD

  Children's National Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: June 24, 2015
• First Posted: June 29, 2015
• Study Start: May 1, 2015
• Primary Completion: May 18, 2018
• Last Updated: March 15, 2023

Record last verified: 2023-03

Locations

US (1)