Phase I Trial of the Selective Inhibitor of Nuclear Export, KPT-330, in Relapsed Childhood ALL and AML
1 other identifier
interventional
16
1 country
10
Brief Summary
This research study involves participants who have acute lymphoblastic or acute myelogenous leukemia that has relapsed or has become resistant (or refractory) to standard therapies. This research study is evaluating a drug called KPT-330. Laboratory and other studies suggest that the study drug, KPT-330, may prevent leukemia cells from growing and may lead to the destruction of leukemia cells. It is thought that KPT-330 activates cellular processes that increase the death of leukemia cells. The main goal of this study is to evaluate the side effects of KPT-330 when it is administered to children and adolescents with relapsed or refractory leukemia.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Mar 2014
Longer than P75 for phase_1
10 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 1, 2014
CompletedFirst Submitted
Initial submission to the registry
March 14, 2014
CompletedFirst Posted
Study publicly available on registry
March 19, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2026
ExpectedDecember 2, 2025
December 1, 2025
3.9 years
March 14, 2014
December 1, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Toxicity profile of KPT-330 assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Toxicities will be tabulated by type and grade.
3 Years
Maximum tolerated dose (MTD) of KPT-330 determined by incidence of dose limiting toxicities.
Toxicities graded by CTCAE version 4.0
2 Years
Secondary Outcomes (3)
Measurement of KPT-330 in the blood, urine and cerebrospinal fluid.
2 Years
Assessment of anti-leukemic activity of KPT-330 measured by objective response rates.
3 Years
Biomarker analysis including measurements of cytokine levels and expression of XPO1 in white blood cells.
3 Years
Study Arms (1)
KPT-330
EXPERIMENTALKPT-330 will be administered twice a week on Days 1 and 3 for four weeks. Starting dose 30 mg/m2.In the dose-escalation cohort, three patients will initially be enrolled at each dose level and will be monitored for a DLT during the 28-day treatment cycle before dose escalation may occur.
Interventions
Eligibility Criteria
You may qualify if:
- Age: Patient must be ≥ 12 months (365 days) and ≤ 21 years.
- Histologically confirmed diagnosis of relapsed or refractory ALL (including Burkitt leukemia), AML, mixed lineage leukemia, biphenotypic leukemia, or chronic myelogenous leukemia (CML) in blast crisis.
- Refractory disease defined as: Persistent disease after at least two induction cycles.
- Relapsed disease: Second or subsequent relapse, any relapse refractory to salvage chemotherapy
- Subjects must have bone marrow with ≥ 5% blasts (M2 or M3 marrow) definitively identified either on a bone marrow aspirate or biopsy sample, as assessed by morphology, immunohistochemical studies, flow cytometry, karyotype, cytogenetic testing such as fluorescent in situ hybridization (FISH) or other molecular studies.
- Subject would not benefit from additional cytotoxic chemotherapy as determined by the treating physician.
- Patients with CNS 1 or CNS 2 disease are eligible. Patients with isolated CNS relapse or CNS 3 disease are not eligible. Please refer to Section 11.1.3 for definitions of CNS disease status and interpretation of traumatic lumbar punctures.
- Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study and meet all of the following criteria:
- Myelosuppressive chemotherapy: 14 days must have elapsed since the completion of myelosuppressive therapy. Individuals may have received any of the following medications within 14 days without a "wash-out" period:
- Standard maintenance therapy (vincristine, 6MP, corticosteroids, low dose methotrexate)
- Hydroxyurea
- Intrathecal chemotherapy with methotrexate, hydrocortisone and/or cytarabine.
- Radiation therapy (XRT):
- Total Body Irradiation (TBI) or craniospinal radiation therapy: Must have been completed more than 90 days from study entry
- Palliative XRT: XRT for chloromas does not require a washout period.
- +15 more criteria
You may not qualify if:
- Inability to take or tolerate enteral medications
- Individuals with CNS 3 leukemia
- Individuals with Down syndrome
- Patients with prior hematopoietic stem cell transplant (HSCT) are eligible, with the exception of the following:
- Autologous HSCT within 60 days of study entry
- Allogeneic HSCT within 90 days of study entry
- Evidence of graft-versus-host-disease (GVHD)
- Treatment with immunosuppressive medications within 14 days; however, weaning or stable doses of steroids (must be ≤ 20 mg/m2/day of prednisone equivalents) and/or calcineurin inhibitors are permitted.
- Treatment with hematopoietic growth factors (G-CSF):
- Long-acting (e.g., Neulasta) within 14 days prior to study entry
- Short-acting (e.g., Neupogen) within 7 days prior to study entry
- Treatment with an investigational agent within 28 days of study entry, or 3 half-lives, whichever is longer.
- Patients will be excluded if there is a plan to administer non-protocol chemotherapy, radiation therapy, or immunotherapy during the study period.
- Any ECG abnormality that in the opinion of the principal investigator would preclude safe participation in the study
- Patients refractory to red blood cell or platelet transfusions.
- +10 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Dana-Farber Cancer Institutelead
- William Lawrence and Blanche Hughes Foundationcollaborator
- Karyopharm Therapeutics Inccollaborator
Study Sites (10)
UCSF
San Francisco, California, 94143, United States
Children's Hospital Colorado
Aurora, Colorado, 80045, United States
Children's Healthcare of Atlanta
Atlanta, Georgia, 30322, United States
Boston Children's Hospital
Boston, Massachusetts, 02115, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Columbia University Medical Center
New York, New York, 10032, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Texas Children's Hospital
Houston, Texas, 77030, United States
Seattle Children's Hospital
Seattle, Washington, 98101, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Andrew E Place, MD,PhD
Dana-Farber Cancer Institute
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
March 14, 2014
First Posted
March 19, 2014
Study Start
March 1, 2014
Primary Completion
February 1, 2018
Study Completion (Estimated)
June 1, 2026
Last Updated
December 2, 2025
Record last verified: 2025-12