Matched Targeted Therapy for High-Risk Leukemia

Not currently recruiting at 16 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatments for high-risk leukemias in children and young adults using specialized testing called leukemia profiling. By analyzing the leukemia's genetic makeup, doctors aim to find and recommend personalized treatments, known as matched targeted therapy, which targets specific genetic changes in cancer cells and could be more effective for each participant. The trial includes two groups: one for those with leukemia that has returned or resisted treatment, and another for those with a new diagnosis of specific types of leukemia. Participants may qualify if they have a history of recurring or newly diagnosed leukemia that hasn't responded well to standard treatments. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could lead to more effective, personalized leukemia treatments.

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 prior data suggests that leukemia profiling is safe for children and young adults?

Research has shown that matched targeted therapy (MTT) for leukemia has been studied before. These studies found that about 14% of patients with relapsed or hard-to-treat leukemia responded to this treatment. This indicates that the therapy can be used safely and can sometimes effectively target specific cancer types. While the results are promising, safety and effectiveness can differ from person to person.

Matched targeted therapies are generally designed to attack cancer cells with certain genetic changes, making them more focused than traditional treatments and potentially leading to fewer side effects. However, like any treatment, there may still be some risks or side effects.

Prospective participants in a clinical trial for MTT should discuss potential risks and benefits with their healthcare provider. This conversation can help clarify how this treatment might work for them and what side effects they might expect based on their specific condition. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about matched targeted therapy for high-risk leukemia because it offers a personalized approach that isn't common with standard treatments like chemotherapy, radiation, or stem cell transplants. Unlike traditional methods that attack all fast-growing cells, this therapy targets specific genetic mutations found in the leukemia cells, potentially leading to more effective and less toxic treatment. By identifying actionable genomic alterations, this approach allows doctors to tailor treatments to the unique genetic profile of each patient's cancer, promising higher precision and possibly better outcomes.

What evidence suggests that this trial's treatments could be effective for high-risk leukemia?

Research has shown that matched targeted therapy (MTT) can help treat certain high-risk types of leukemia. In this trial, participants with relapsed or refractory leukemia, including acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), will receive MTT based on specific genetic changes identified in their cancer cells. One study found that 14% of patients with leukemia that had returned or was not responding to other treatments showed improvement after receiving MTT. For conditions like myelodysplastic syndromes (MDS) and AML, targeting these genetic changes can influence treatment choices and outcomes. While the success rate can vary, this personalized treatment approach offers hope for those facing difficult forms of leukemia. ^{1 2 6 7 8}

Who Is on the Research Team?

Yana Pikman, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8178162/

Matched Targeted Therapy for Pediatric Patients with ... We describe clinical responses in the 14% of patients with relapsed/refractory leukemia who received the matched targeted therapy.

2. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT02670525

Matched Targeted Therapy For High-Risk Leukemias and ... This research study is seeking to gain new knowledge about Recurrent, Refractory, or High Risk Leukemias in children and young adults.

3. asco.org asco.org/abstracts-presentations/ABSTRACT494082

Target therapy adoption for myelodysplastic syndromes ... This study evaluates MT use in first-line therapy decisions and its impact on treatment for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).

4. haematologica.org haematologica.org/article/view/11858

Treatment of high-risk myelodysplastic syndromes In 435 HR-MDS patients in whom HMA treatment failed, the median survival was only 5.6 months and the 2-year overall response rate was 15%.

5. ehoonline.biomedcentral.com ehoonline.biomedcentral.com/articles/10.1186/s40164-025-00678-9

Advances and challenges in the treatment of myelodysplastic ... As a result, current therapies for MDS are little more than palliative, with a 5 year survival rate of ~ 37% [1]. MDS develops from an ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12002404/

Myelodysplastic syndromes: 2023 update on diagnosis ... In this study patients treated with ESA had a better survival (HR for death was 0.43, 95% CI 0.25–0.72). Results from a recently published randomized placebo- ...

7. targetedonc.com targetedonc.com/view/emerging-therapies-are-explored-in-low--and-high-risk-mds

Emerging Therapies Are Explored in Low- and High-Risk ... In a retrospective series with a median follow‐up of 7 years, approximately 50% of patients had refractory disease and 26% relapsed after an ...

8. ashpublications.org ashpublications.org/blood/article/145/18/2002/535065/How-I-treat-higher-risk-MDS

How I treat higher-risk MDS | Blood - ASH Publications A phase 3 trial comparing AZA with supportive care in MDS demonstrated a median time to leukemic transformation or death of 21 months with AZA, ...