KPT-330 for Relapsed Childhood Leukemia

Recruiting at 9 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Immunosuppressants, Growth factors

Disqualifiers: Down syndrome, CNS 3 leukemia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks per cycle

16 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new drug, KPT-330, for children and teens with acute leukemia that has returned or isn't responding to standard treatments. The goal is to determine if KPT-330 can halt the growth of leukemia cells and lead to their destruction. Participants will provide insights into the drug's side effects. This trial may suit young people whose leukemia has returned or resisted treatment, with significant cancer cell presence in the bone marrow. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, certain treatments like immunotherapy, monoclonal antibodies, and investigational agents have specific waiting periods before joining the study. It's best to discuss your current medications with the study team.

Is there any evidence suggesting that KPT-330 is likely to be safe for humans?

Research has shown that KPT-330, also known as selinexor, has been studied for human safety. Previous studies tested its ability to stop cancer cells from growing and even destroy them. Some research has examined how well patients tolerate KPT-330 and what side effects may occur.

For example, in one study, researchers determined the highest safe dose of KPT-330 by closely monitoring side effects. Another study suggested that KPT-330 might improve outcomes in certain types of leukemia.

While specific details on side effects from these studies weren't provided, the progression to human trials indicates some confidence in its safety. However, as this is still an early phase trial, more information will be collected to understand all possible side effects. Participants should consider this when deciding to join the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard chemotherapy treatments for relapsed childhood leukemia, KPT-330 offers a novel approach by targeting a specific protein involved in cancer cell survival. This treatment works differently by inhibiting XPO1, a protein that helps cancer cells grow and evade the immune system. Researchers are excited about KPT-330 because it has the potential to overcome resistance to existing therapies, providing a new option for patients who have not responded well to traditional treatments.

What evidence suggests that KPT-330 might be an effective treatment for relapsed childhood leukemia?

Research suggests that KPT-330, also known as selinexor, might help treat children with leukemia that has returned or is difficult to treat. Studies have found that KPT-330 works by blocking a protein called exportin 1 (XPO1), which cancer cells need to grow. Blocking XPO1 makes leukemia cells more likely to die. In animal studies, KPT-330 slowed the growth of leukemia cells and improved survival rates. This drug has shown promise in early tests with children who have difficult-to-treat leukemia. Although more research is needed, these findings suggest that KPT-330 could help manage challenging cases of childhood leukemia. Participants in this trial will receive KPT-330 to further evaluate its effectiveness and safety in treating relapsed childhood leukemia. ^{1 2 4 6 7}

Who Is on the Research Team?

Andrew Place, MD, PhD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for children and adolescents aged between 1 and 21 years with relapsed or refractory acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML), including other specific types of leukemia. Participants must have recovered from previous treatments, not be pregnant, agree to use contraception, and have no severe concurrent diseases.

Inclusion Criteria

My brain or spinal cord disease is at a manageable stage.

I have recovered from side effects of my previous cancer treatments.

I agree not to breastfeed while participating in this study.

Exclusion Criteria

I do not plan to receive any non-study cancer treatments during the trial.

I have not taken certain medications recently.

I need more chemotherapy to help treat my condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive KPT-330 twice a week on Days 1 and 3 for four weeks per cycle, with dose escalation to determine the maximum tolerated dose

4 weeks per cycle

Multiple visits per week for physical exams and blood work

Follow-up

Participants are monitored for safety and effectiveness after treatment, including pharmacokinetic and pharmacodynamic sample collection

2-3 years

What Are the Treatments Tested in This Trial?

Interventions

• KPT-330

Trial Overview The study tests KPT-330's effectiveness on participants with certain types of leukemia that haven't responded to standard therapies. The focus is on understanding the side effects when given to young patients. It explores how KPT-330 might help in destroying cancer cells by activating cell death processes.

How Is the Trial Designed?

Group I: KPT-330 Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

William Lawrence and Blanche Hughes Foundation

Collaborator

Trials

1

Recruited

20+

Karyopharm Therapeutics Inc

Industry Sponsor

Trials

89

Recruited

7,200+

Richard Paulson

Karyopharm Therapeutics Inc

Chief Executive Officer since 2021

MBA from the University of Toronto's Rotman School of Management

Reshma Rangwala

Karyopharm Therapeutics Inc

Chief Medical Officer since 2023

MD, PhD

Published Research Related to This Trial

The cure rate for childhood acute lymphoblastic leukemia (ALL) has surpassed 90% in recent clinical trials, but further improvements will depend on molecular therapies and precise risk stratification rather than just increasing chemotherapy doses.

Specific genetic markers, such as ETV6-RUNX1 and Philadelphia chromosome positivity, guide treatment decisions, with targeted therapies like dasatinib and venetoclax showing promise for high-risk subtypes, while innovative treatments like CAR-T cell therapy are being explored for better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Precision medicine in acute lymphoblastic leukemia. Pui, CH.[2022]

A study evaluated the sensitivity of 6 childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cell lines to 10 anticancer drugs, revealing that the relapse-derived cell line YCUB-5R was more resistant to several key drugs compared to the diagnosis-derived cell line YCUB-5.

Etoposide and SN-38 (irinotecan) demonstrated the highest efficacy in inhibiting cell growth, suggesting they could be promising candidates for developing new therapies for childhood BCP-ALL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemo-sensitivity in a panel of B-cell precursor acute lymphoblastic leukemia cell lines, YCUB series, derived from children. Goto, H., Naruto, T., Tanoshima, R., et al.[2013]

Novel agents like bispecific antibodies (blinatumomab and inotuzumab ozogamicin) targeting CD19 and CD22 are showing promise in treating relapsed and refractory B-cell precursor acute lymphoblastic leukaemia (BCP-ALL), potentially offering less toxic options compared to traditional therapies.

Targeted therapies for specific genetic subtypes of leukaemia, such as KMT2A-rearranged leukaemias and BCR-ABL-positive ALL, are being developed, but the pace of new drug approvals for pediatric cancers remains slower than for adults, highlighting the need for prioritization and international collaboration in research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted inhibitors and antibody immunotherapies: Novel therapies for paediatric leukaemia and lymphoma. Brivio, E., Baruchel, A., Beishuizen, A., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4994896/

Activity of a selective inhibitor of nuclear export, selinexor ... Using an immunosuppressed mouse model bearing primary patient-derived AML cells, we demonstrate that selinexor (KPT-330), an oral antagonist of XPO1 that is ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02212561

Study Details | NCT02212561 | Selinexor With Fludarabine ... The purpose of this study is to test the safety of selinexor (KPT-330) and to find the highest dose of selinexor (KPT-330) that can be given safely when it ...

3. hematologyadvisor.com hematologyadvisor.com/reports/xpo1-inhibition-selinexor-acute-myeloid-leukemia-pediatric-patients-treatment/

XPO1 Inhibition With Selinexor Promising in R/R AML ... The selective exportin 1 (XPO1) inhibitor selinexor (KPT-330) showed promise in improving survival rates among pediatric patients with relapsed or refractory ( ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4722540/

a report from the Pediatric Preclinical Testing Program - PMC Selinexor (KPT-330) is an inhibitor of the major nuclear export receptor, exportin 1 (XPO1, also termed chromosome region maintenance 1, CRM1) that has ...

5. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.2016.67.5066

Phase I Study of Selinexor, a Selective Inhibitor of Nuclear ... Selinexor, in combination with fludarabine and cytarabine, is tolerable at doses up to 55 mg/m 2 in pediatric patients with relapsed or refractory leukemia.

6. childrenshospital.org childrenshospital.org/clinical-trials/nct02091245

NCT02091245 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.

7. withpower.com withpower.com/clinical-trials/for-childhood-leukemia

Top Childhood Leukemia Clinical Trials | Power 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 ...