Relapsed Acute Lymphoblastic Leukemia (ALL)Phase 1NCT02091245
Phase I Trial of the Selective Inhibitor of Nuclear Export, KPT-330, in Relapsed Childhood ALL and AML
A Phase 1 study testing KPT-330 in people with Relapsed Acute Lymphoblastic Leukemia (ALL) and Refractory Acute Lymphoblastic Leukemia (ALL), run by Dana-Farber Cancer Institute at 10 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 months to 21 years
- Conditions the study is for
- Relapsed Acute Lymphoblastic Leukemia (ALL), Refractory Acute Lymphoblastic Leukemia (ALL), Relapsed Acute Myelogenous Leukemia (AML)
- What is being tested?
- KPT-330
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 10 sitesUnited States
- Study dates
- Mar 2014to Dec 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 months to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Show all 56Show fewer
- 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.
- Biologic (anti-neoplastic agent): At least 7 days after the last dose of a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair.
- Immunotherapy: At least 6 weeks after the completion of any type of immunotherapy, e.g. tumor vaccines and chimeric antigen receptor T-cells.
- Monoclonal antibodies: At least 3 half-lives of the antibody after the last dose of a monoclonal antibody. (See table on DVL homepage listing monoclonal antibody half-lives: https://members.childrensoncologygroup.
- Performance status:
- -- Lansky ≥ 50 for individuals 18 months- ≤ 16 years old; Karnofsky > 50% for individuals 17-21 years old (See Appendix I).
- Adequate organ function defined as the following:
- Direct bilirubin ≤1.5 X institutional upper limit of normal (ULN)
- AST (SGOT)/ALT (SGPT) ≤ 3X institutional ULN
- Creatinine below institutional ULN or creatinine clearance ≥ 60 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal
- Echocardiogram must have a shortening fraction or an ejection fraction greater than institutional lower limit of normal for age and gender. Echocardiogram must be obtained while patient is not receiving cardiotropic medications (eg., pressors or afterload reducers).
- Oxygen saturation over 90% by pulse oximetry without administration of supplemental oxygen.
- Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed prior to enrollment.
- Female patients with infants must agree not to breastfeed their infants while on this study.
- The effects of KPT-330 on the developing human fetus are unknown. For this reason and because many chemotherapeutic agents are known to be teratogenic, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- Ability of participant (or parent/guardian for participants who are minors) to understand and the willingness to sign the written informed consent document.
- Exclusion Criteria:Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study.
- 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.
- Patients receiving anti-coagulation therapy are eligible as long as anti-coagulation regimen has been stable for > 1 month.
- Patients with systemic fungal, bacterial, viral or other infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment.
- For dose-escalation cohort only, known positivity for human immunodeficiency virus (HIV); baseline testing for HIV is not required. HIV positive patients will be eligible for the dose-expansion cohort.
- Known active hepatitis A, B, or C infection; or known to be positive for HCV RNA or HBsAg (HBV surface antigen); baseline testing for viral hepatitis is not required.
- Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of KPT-330 (e.g. ulcerative colitis, uncontrolled nausea, vomiting, diarrhea, malabsorption or history of small bowel resection)
- Individuals with significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.
- Individuals with a history of a different malignancy (other than acute leukemia) are ineligible except for the following circumstances: Individuals are eligible if the different malignancy is in complete remission at the time of study entry.
- Pregnant women are excluded from this study because KPT-330 is a chemotherapeutic agent with unknown teratogenic or abortifacient effects.
- Individuals who are eligible for allogeneic hematopoietic stem cell transplantation (HSCT) as determined by the treating physician, and have a suitable donor or appropriate stem cell source available
- Individuals who would benefit from additional cytotoxic chemotherapy as determined by the treating physician
Who cannot join
None listed.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Children's Healthcare of Atlanta
Atlanta, Georgia, 30322
Children's Hospital Colorado
Aurora, Colorado, 80045
Boston Children's Hospital
Boston, Massachusetts, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Texas Children's Hospital
Houston, Texas, 77030
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
Columbia University Medical Center
New York, New York, 10032
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
UCSF
San Francisco, California, 94143
Seattle Children's Hospital
Seattle, Washington, 98101
About this study
Official title: Phase I Trial of the Selective Inhibitor of Nuclear Export, KPT-330, in Relapsed Childhood ALL and AML.
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.
Read the detailed description
The investigators are trying to determine a safe dose of KPT-330 and will be giving participants different dose levels of the study drug. Three to six participants will receive the starting dose of the drug. If the side effects are not too severe, the next group of participants will take the study drug at a higher dose level. Up to 3 dose levels of the study drug will be tested, but once each participant has been assigned a dose level, the participant will always receive the same dose. The highest dose that people can be given safely is called the maximum tolerated dose (MTD). Once the MTD is determined, up to 10 additional participants will receive that dose to further study the drug.
Participants between the age of ≥18 months (540 days) and ≤ 21 years with relapsed (second or subsequent relapse) or refractory ALL or AML will be eligible to enroll. KPT-330 will be administered twice a week on Days 1 and 3 for four weeks (a cycle is 4 weeks). All participants will receive intrathecal chemotherapy on Day 1 of each cycle. Participants with CNS-2 disease will receive additional doses of IT chemo. Pharmacokinetic (PK) samples will be collected during Cycle 1 on Days 1-3 and 15. PK samples will be collected during Cycle 2 on Day 15. Pharmacodynamic (PD) samples will be collected during Cycle 1 on Days 1-3. PD samples will be collected during Cycle 2 on Day 15. Additional optional correlative biology sample will be collected. Participants are monitored closely for adverse events. Participants will have physical exams and blood work more than once a week during all cycles.
- Conditions
- Relapsed Acute Lymphoblastic Leukemia (ALL), Refractory Acute Lymphoblastic Leukemia (ALL), Relapsed Acute Myelogenous Leukemia (AML), Refractory Acute Myelogenous Leukemia (AML), Relapsed Mixed Lineage Leukemia, Refractory Mixed Lineage Leukemia
- Being tested
- KPT-330
- Keywords
- Relapsed acute lymphoblastic leukemia (ALL), Refractory acute lymphoblastic leukemia (ALL), Relapsed acute myelogenous leukemia (AML), Refractory acute myelogenous leukemia (AML), Relapsed childhood leukemia, Relapsed mixed lineage leukemia, Refractory mixed lineage leukemia, Relapsed biphenotypic leukemia, Refractory biphenotypic leukemia, Chronic myelogenous leukemia (CML) in blast crisis
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Leukemia, Myelogenous, Chronic, BCR-ABL Positive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KPT-330Drug
Also called Selinexor
| Study group | Role | What they receive |
|---|---|---|
| KPT-330 | Experimental | KPT-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. Receives: Drug: KPT-330 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3 Years
Maximum tolerated dose (MTD) of KPT-330 determined by incidence of dose limiting toxicities.
Toxicities graded by CTCAE version 4.0
Measured: 2 Years
Secondary outcomes (3)
Measurement of KPT-330 in the blood, urine and cerebrospinal fluid.
Pharmacokinetic analysis
Measured: 2 Years
Assessment of anti-leukemic activity of KPT-330 measured by objective response rates.
Measured: 3 Years
Biomarker analysis including measurements of cytokine levels and expression of XPO1 in white blood cells.
Pharmacodynamic analysis
Measured: 3 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2014 (estimated)
- Study startMar 2014
- Primary completionFeb 2018
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed Acute Lymphoblastic Leukemia (ALL)Studies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- William Lawrence and Blanche Hughes Foundation, Karyopharm Therapeutics Inc
- Responsible party
- Principal investigator, Andrew E. Place, MD, Dana-Farber Cancer Institute
- Investigators
- Andrew E Place, MD,PhD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02091245
- Sponsor's protocol ID
- 13-563
- Status last verified
- May 2026
- First submitted
- 14 Mar 2014
- Last updated
- 29 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial of the Selective Inhibitor of Nuclear Export, KPT-330, in Relapsed Childhood ALL and AML.
- ClinicalTrials.gov ID
- NCT02091245
- Acronym / sponsor ID
- 13-563
- Conditions
- Relapsed Acute Lymphoblastic Leukemia (ALL), Refractory Acute Lymphoblastic Leukemia (ALL), Relapsed Acute Myelogenous Leukemia (AML), Refractory Acute Myelogenous Leukemia (AML), Relapsed Mixed Lineage Leukemia, Refractory Mixed Lineage Leukemia
- Keywords
- Relapsed acute lymphoblastic leukemia (ALL), Refractory acute lymphoblastic leukemia (ALL), Relapsed acute myelogenous leukemia (AML), Refractory acute myelogenous leukemia (AML), Relapsed childhood leukemia, Relapsed mixed lineage leukemia, Refractory mixed lineage leukemia, Relapsed biphenotypic leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- William Lawrence and Blanche Hughes Foundation, Karyopharm Therapeutics Inc
- Study start
- Mar 2014 (actual)
- Primary completion
- Feb 2018 (actual)
- Study completion
- Dec 2026 (estimated)
- First posted
- 19 Mar 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The investigators are trying to determine a safe dose of KPT-330 and will be giving participants different dose levels of the study drug. Three to six participants will receive the starting dose of the drug. If the side effects are not too severe, the next group of participants will take the study drug at a higher dose level. Up to 3 dose levels of the study drug will be tested, but once each participant has been assigned a dose level, the participant will always receive the same dose. The highest dose that people can be given safely is called the maximum tolerated dose (MTD). Once the MTD is determined, up to 10 additional participants will receive that dose to further study the drug.
Participants between the age of ≥18 months (540 days) and ≤ 21 years with relapsed (second or subsequent relapse) or refractory ALL or AML will be eligible to enroll. KPT-330 will be administered twice a week on Days 1 and 3 for four weeks (a cycle is 4 weeks). All participants will receive intrathecal chemotherapy on Day 1 of each cycle. Participants with CNS-2 disease will receive additional doses of IT chemo. Pharmacokinetic (PK) samples will be collected during Cycle 1 on Days 1-3 and 15. PK samples will be collected during Cycle 2 on Day 15. Pharmacodynamic (PD) samples will be collected during Cycle 1 on Days 1-3. PD samples will be collected during Cycle 2 on Day 15. Additional optional correlative biology sample will be collected. Participants are monitored closely for adverse events. Participants will have physical exams and blood work more than once a week during all cycles.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| KPT-330 | Experimental | Drug: KPT-330KPT-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. |
Who may qualify
- Ages
- 12 months to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (56 listed)
- 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.
- 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.
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KPT-330Also: Selinexor | Drug | KPT-330 |
Primary outcome
Toxicity profile of KPT-330 assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Time frame: 3 Years
Toxicities will be tabulated by type and grade.
Maximum tolerated dose (MTD) of KPT-330 determined by incidence of dose limiting toxicities.
Time frame: 2 Years
Toxicities graded by CTCAE version 4.0
3 secondary outcomes
Measurement of KPT-330 in the blood, urine and cerebrospinal fluid.
Time frame: 2 Years
Assessment of anti-leukemic activity of KPT-330 measured by objective response rates.
Time frame: 3 Years
Biomarker analysis including measurements of cytokine levels and expression of XPO1 in white blood cells.
Time frame: 3 Years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2026.
Related trials for Relapsed Acute Lymphoblastic Leukemia (ALL)
Not yet recruitingPhase 1
A Study to Assess the Pharmacokinetics and Safety of Revumenib in Participants With Advanced Cancer and Hepatic or Renal Impairment
Relapsed/Refractory (R/R) Hematologic Malignancies, Acute Leukemia
Active, not recruitingEarly Phase 1
Iomab-ACT: A Pilot Study of 131-I Apamistamab Followed by CD19-Targeted CAR T-Cell Therapy for Patients With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia or Diffuse Large B-Cell Lymphoma
B-ALL, DLBCL
Active, not recruitingPhase 2
Valemetostat Tosylate (DS-3201b), an Enhancer of Zeste Homolog (EZH) 1/2 Dual Inhibitor, for Relapsed/Refractory Peripheral T-Cell Lymphoma (VALENTINE-PTCL01)
Relapsed/Refractory Peripheral T-Cell Lymphoma, Adult T Cell Leukemia/Lymphoma
RecruitingPhase 1
A Phase I Dose Finding Study of MB-CART2219.1
Lymphoma, CLL
Not yet recruitingPhase 1
BLinatumomab and iNKT in Relapsed B-Cell ALL
B-Cell ALL, ALL (Acute B-Lymphoblastic Leukemia)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrew E Place, MD,PhD principal investigator
Dana-Farber Cancer Institute
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing KPT-330 in people with Relapsed Acute Lymphoblastic Leukemia (ALL) and Refractory Acute Lymphoblastic Leukemia (ALL), run by Dana-Farber Cancer Institute at 10 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 56 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 29 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Toxicity profile of KPT-330 assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (time frame: 3 Years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 May 2026.