Matched Targeted Therapy for High-Risk Leukemia

Recruiting at 14 trial locations

Overseen By Andrew Place, MD, PhD

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Dana-Farber Cancer Institute

Disqualifiers: Insufficient specimen, others

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

Compensation: Varies

Number of Visits: Unknown

338 Participants Needed

Trial Summary

What is the purpose of this trial?

This research study is seeking to gain new knowledge about Recurrent, Refractory, or High Risk Leukemias in children and young adults. This study is evaluating the use of specialized testing called leukemia profiling. Once the profiling is performed, the results are evaluated by an expert panel of physicians, scientists and pharmacists. This may result in a recommendation for a specific cancer therapy or a clinical trial called matched targeted therapy (MTT). The results of the leukemia profiling and, if applicable, the MTT recommendation will be communicated to the participant's primary oncologist.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your primary oncologist.

What data supports the effectiveness of the treatment Matched Targeted Therapy for high-risk leukemia?

Research shows that targeted therapies, which are designed to act on specific genetic changes in cancer cells, have been promising in treating high-risk pediatric leukemia. These therapies can be more effective and less harmful than traditional chemotherapy, especially when used in combination with other treatments. ^{1 2 3 4 5}

What safety data exists for targeted therapies in leukemia and other conditions?

Targeted therapies, including those for leukemia, can lead to treatment-related toxicities like febrile neutropenia (fever with low white blood cell count), hypertension (high blood pressure), and thrombocytopenia (low platelet count), which may require hospitalization. In other conditions, targeted therapies have been associated with cardiovascular and immune-related adverse events, but they generally show improved safety compared to traditional chemotherapy. ^{6 7 8 9 10}

How is Matched Targeted Therapy different from other treatments for high-risk leukemia?

Matched Targeted Therapy is unique because it is designed to specifically target the genetic and molecular features of high-risk leukemia, potentially making it more effective and less toxic than traditional chemotherapy. This approach takes advantage of the understanding of genetic signatures and the synergy between targeted therapies and conventional treatments, offering a personalized treatment option for patients. ^{2 3 5 11 12}

Research Team

Yana Pikman, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

This trial is for children and young adults up to 30 years old with high-risk leukemias or myelodysplastic syndrome (MDS), including those who have relapsed, are refractory to treatment, or newly diagnosed with certain types. Participants must have a confirmed diagnosis and sufficient leukemia samples available for profiling.

Inclusion Criteria

I am diagnosed with a condition that fits into one of the study's specific groups.

My leukemia has returned or didn't respond to initial treatment.

I have a new diagnosis of a rare or specific type of leukemia and am not eligible for a stem cell transplant.

Exclusion Criteria

I don't have enough leukemia samples for testing or my blood tests show less than 20% cancer cells and no further tests are planned.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Leukemia Profiling

Leukemia cells are tested for cancer-causing alterations to identify actionable genomic alterations and make a matched targeted therapy treatment recommendation

2 weeks

Matched Targeted Therapy Recommendation

Based on profiling results, a matched targeted therapy is recommended and communicated to the participant's primary oncologist

2 weeks

Follow-up

Participants are monitored for safety and effectiveness after receiving the matched targeted therapy

2 years

Treatment Details

Interventions

• Matched Targeted Therapy

Trial Overview The study focuses on leukemia profiling to identify specific cancer therapies tailored to the patient's unique condition. An expert panel reviews the results, which may lead to recommendations for matched targeted therapy (MTT) that will be shared with the participant's primary oncologist.

Participant Groups

Group I: Relapsed/Refractory Leukemia Experimental Treatment 1 Intervention

Cohort 1: Relapsed/Refractory Leukemia * Acute lymphoblastic leukemia (ALL), first or greater relapse * Acute myeloid leukemia (AML), first or greater relapse * Leukemia refractory to induction chemotherapy * Other recurrent leukemia * Myelodysplastic syndrome (MDS), first or greater relapse, or refractory to initial therapy After the screening procedures confirms patient eligibility: * Leukemia Profiling will be performed * Identifying an actionable genomic alteration and making a matched targeted therapy treatment recommendation.

Group II: New Diagnosis Experimental Treatment 1 Intervention

Cohort 2: New Diagnosis * Acute myeloid leukemia (AML), new diagnosis (excluding acute promyelocytic leukemia (APL)) * New diagnosis infant mixed-lineage leukemia (MLL)-rearranged ALL or low hypodiploid (\<40 chromosomes) ALL * Rare leukemia- e.g., juvenile myelomonocytic leukemia (JMML), leukemia of ambiguous lineage * Secondary leukemia * Myelodysplastic syndrome (MDS) not eligible for stem cell transplant After the screening procedures confirms eligibility: * Leukemia Profiling will be performed * Identifying an actionable genomic alteration and making a matched targeted therapy treatment recommendation.

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Findings from Research

In a network meta-analysis of six phase III clinical trials involving 4053 patients, PD-L1 inhibitor monotherapy was found to significantly reduce the risk of treatment-related adverse events (AEs) compared to platinum-based chemotherapy, with a risk ratio of 0.722 for any grade AEs and 0.406 for grade 3-5 AEs.

While PD-L1 inhibitors showed improved safety outcomes overall, they were associated with a higher risk of immune-related AEs compared to chemotherapy, indicating a need for careful monitoring in patients receiving this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-L1 Inhibitors as Monotherapy for the First-Line Treatment of Non-Small-Cell Lung Cancer in PD-L1 Positive Patients: A Safety Data Network Meta-Analysis. García Campelo, MR., Arriola, E., Campos Balea, B., et al.[2021]

Febrile neutropenia, hypertension, and thrombocytopenia are the most common treatment-related toxicities (TRTs) in children and young adults with acute lymphoblastic leukemia (ALL), highlighting the significant health challenges these patients face.

Adolescents and young adults (AYAs) experience longer hospital stays for TRTs and have worse survival outcomes when treated at non-specialized cancer centers, indicating the need for improved care strategies in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment-related toxicities associated with hospitalization in children, adolescents, and young adults with acute lymphoblastic leukemia: population level analysis. Namjoshi, NS., Keegan, THM., Li, QC., et al.[2023]

References

1. China pubmed.ncbi.nlm.nih.gov

[Advances in targeted therapy for childhood acute myeloid leukemia]. [2020]

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

Targeted therapies for the treatment of leukemia. [2019]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Targeted drug discovery for pediatric leukemia. [2021]

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

Personalized medicine for patients with advanced cancer in the phase I program at MD Anderson: validation and landmark analyses. [2022]

5. France pubmed.ncbi.nlm.nih.gov

Immunotherapies in acute leukemia. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

PD-L1 Inhibitors as Monotherapy for the First-Line Treatment of Non-Small-Cell Lung Cancer in PD-L1 Positive Patients: A Safety Data Network Meta-Analysis. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Cardiovascular Toxicity With PD-1/PD-L1 Inhibitors in Cancer Patients: A Systematic Review and Meta-Analysis. [2022]

8. France pubmed.ncbi.nlm.nih.gov

When targeted therapy for cancer leads to ICU admission. RETRO-TARGETICU multicentric study. [2023]

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

Pharmacovigilance Analysis of Cardiac Toxicities Associated With Targeted Therapies for Metastatic NSCLC. [2023]

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

Treatment-related toxicities associated with hospitalization in children, adolescents, and young adults with acute lymphoblastic leukemia: population level analysis. [2023]

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

Targeted therapies for high-risk acute myeloid leukemia. [2019]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Emerging antibody-based therapies for the treatment of acute myeloid leukemia. [2022]