KPT-330 for Relapsed Childhood Leukemia

Recruiting at 9 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Dana-Farber Cancer Institute

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

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the drug KPT-330 for relapsed childhood leukemia?

The research highlights the potential of targeted therapies for KMT2A-rearranged leukemias, which are known to have a poor prognosis. While KPT-330 is not directly mentioned, the study on proteasome inhibition shows a 90% response rate in relapsed/refractory KMT2A patients, suggesting that targeted approaches can be effective in similar contexts. ^{1 2 3 4 5}

How does the drug KPT-330 differ from other treatments for relapsed childhood leukemia?

KPT-330, also known as selinexor, is unique because it works by blocking a protein that helps cancer cells grow and survive, which is different from traditional chemotherapy that directly kills cancer cells. This novel mechanism of action may offer a new approach for treating relapsed childhood leukemia, especially when standard treatments are not effective. ^{2 4 6 7 8}

Research Team

Andrew Place, MD, PhD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Proteasome inhibition targets the KMT2A transcriptional complex in acute lymphoblastic leukemia. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Chemo-sensitivity in a panel of B-cell precursor acute lymphoblastic leukemia cell lines, YCUB series, derived from children. [2013]

3. United States pubmed.ncbi.nlm.nih.gov

Updates in infant acute lymphoblastic leukemia and the potential for targeted therapy. [2023]

4. China pubmed.ncbi.nlm.nih.gov

Precision medicine in acute lymphoblastic leukemia. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Targeted inhibitors and antibody immunotherapies: Novel therapies for paediatric leukaemia and lymphoma. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Blinatumomab Added to Chemotherapy in Infant Lymphoblastic Leukemia. [2023]

7. Japan pubmed.ncbi.nlm.nih.gov

Evolution and optimization of therapies for acute lymphoblastic leukemia in infants. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Genetic characteristics and treatment outcome in infants with KMT2A germline B-cell precursor acute lymphoblastic leukemia: Results of MLL-Baby protocol. [2023]