Matched Targeted Therapy, Recurrent, Refractory, or High Risk Leukemias
Conditions
Keywords
Recurrent, Refractory, or High Risk Leukemias, Matched targeted therapy
Brief summary
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.
Detailed description
Our tissues and organs are made up of cells. Cancer occurs when the molecules that normally control cell growth are damaged. The damage results in unchecked cell growth which causes a tumor, a collection of cancer cells. The damage is referred to as an alteration. There are different types of cancer-causing alterations. Genes are the part of cells that contain the instructions which tell our cells how to make the right proteins to grow and work. Genes are composed of Deoxyribonucleic Acid (DNA) letters that spell out these instructions. By participating in this study, the participant's leukemia cells will be tested for cancer causing alterations. This testing is called leukemia profiling. The leukemia profiling will be performed using bone marrow or blood that has already been obtained during a clinical test. Alternately, the profiling may be done on leukemia cells that are planned to be obtained as part of routine clinical care. This study will determine whether it is possible to use profiling results to determine a matched targeted therapy for patients with leukemia. It will describe the range of mutations found in patients with leukemia with this type of profiling, and describe the clinical outcomes of patients who receive a matched targeted therapy.
Interventions
GENETICLeukemia Profiling
Genetic profiling of leukemia cells will be performed and analyzed by an expert panel. Matched targeted therapy recommendation based on profiling results will be made if available. The recommendation, if available, will be communicated to the primary oncologist.
Sponsors
Dana-Farber Cancer Institute
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 30 Years
Healthy volunteers
No
Inclusion criteria
* Birth to ≤ 30 years at study entry * Diagnosis: Patients will be enrolled in one of the two cohorts based on diagnosis: 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 Cohort 2: New diagnosis * Acute myeloid leukemia (AML), new diagnosis * 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 Pathologic Criteria * Histologic confirmation of leukemia at the time of diagnosis or recurrence Specimen Samples * Sufficient leukemia specimen available for profiling from diagnosis or recurrence OR bone marrow aspirate/blood draw/pheresis/other fresh sample of patient leukemia cells planned for clinical care anticipated to allow collection of minimum specimen for testing.
Exclusion criteria
* Insufficient leukemia specimen available for profiling from diagnosis or recurrence; or bone marrow evaluation/blood draw/other leukemia cell sample NOT planned to be obtained for clinical care; or peripheral blast percentage \<20% AND clinical blood draw not planned.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Patients With Actionable Alterations | Actionable alteration was identified based on a combination of fluorescence in situ hybridization (FISH)/cytogenetics and sequencing. Average time to full results was 2 weeks. | An actionable alteration was defined as a cancer-associated genomic event for which there was a targeted drug available. Actionable genetic alterations were identified by a combination of standard-of-care cytogenetics/fluorescence in situ hybridization (FISH) and sequencing performed as part of the study. This study is considered feasible if at least 13% of participants analyzed have profile data and identifiable actionable alterations. A 90% exact binomial confidence interval is presented for the rate of patients with actionable alterations to compare the observed rate against 13%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Somatic Genomic Alterations | 2 Years | This Secondary Outcome will be addressed by describing the somatic genomic alterations in Cohort 1 (Relapsed/Refractory Leukemia arm) and Cohort 2 (New Diagnosis arm) that are discovered by genomic analyses. |
| Rate of Results Reporting | 2 Years | This Secondary Outcome will be addressed by a description of the time of results reporting. Documentation of the time of sample receipt and processing, resources and personnel utilized at each step of the process, time to results reporting, interpretation and review by Expert panel and communication of results to the primary oncologist will be captured. |
| Parent's Feelings and Understanding of Genomic Testing | 2 Years | This Secondary Outcome will be addressed by describing the hopes and concerns of parents of children with recurrent/refractory/high-risk de novo leukemia regarding genomic testing of their child's leukemia as well as their understanding of the testing and evaluate whether the hopes and concerns were realized following the return of results. |
| Analysis of Primary Leukemia Sensitivity Testing and Establishment of Xenograft Models | 2 Years | This Secondary Outcome will be addressed by completing analysis of the primary leukemia sensitivity testing to a panel of drugs or shRNA and establishing xenograft models in dedicated participating research laboratories and conducting co-clinical trials with the recommended matched therapy once the animal model is established. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORYana Pikman, MD
Dana-Farber Cancer Institute
Participant flow
Recruitment details
Patients enrolled from August 17, 2016 to May 4, 2022.
Participants by arm
| Arm | Count |
|---|---|
| Relapsed/Refractory Leukemia 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.
Leukemia Profiling: Genetic profiling of leukemia cells will be performed and analyzed by an expert panel. Matched targeted therapy recommendation based on profiling results will be made if available. The recommendation, if available, will be communicated to the primary oncologist. | 236 |
| New Diagnosis 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.
Leukemia Profiling: Genetic profiling of leukemia cells will be performed and analyzed by an expert panel. Matched targeted therapy recommendation based on profiling results will be made if available. The recommendation, if available, will be communicated to the primary oncologist. | 102 |
| Total | 338 |
Baseline characteristics
| Characteristic | New Diagnosis | Total | Relapsed/Refractory Leukemia |
|---|---|---|---|
| Age, Continuous | 10.2 years | 11.1 years | 11.3 years |
| Age, Customized Age (years) at sample 10-17 years | 33 Participants | 127 Participants | 94 Participants |
| Age, Customized Age (years) at sample >=18 years | 19 Participants | 63 Participants | 44 Participants |
| Age, Customized Age (years) at sample 1-9 years | 40 Participants | 131 Participants | 91 Participants |
| Age, Customized Age (years) at sample <1 years | 10 Participants | 17 Participants | 7 Participants |
| Disease AML | 70 Participants | 159 Participants | 89 Participants |
| Disease B-cell ALL | 1 Participants | 112 Participants | 111 Participants |
| Disease Infant MLL rearranged ALL | 4 Participants | 6 Participants | 2 Participants |
| Disease JMML | 2 Participants | 4 Participants | 2 Participants |
| Disease Leukemia of ambiguous lineage | 8 Participants | 16 Participants | 8 Participants |
| Disease MDS | 2 Participants | 6 Participants | 4 Participants |
| Disease Other rare leukemia | 4 Participants | 6 Participants | 2 Participants |
| Disease Secondary leukemia | 9 Participants | 13 Participants | 4 Participants |
| Disease T-cell ALL | 2 Participants | 16 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 16 Participants | 59 Participants | 43 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 75 Participants | 219 Participants | 144 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 11 Participants | 60 Participants | 49 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 9 Participants | 24 Participants | 15 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 33 Participants | 19 Participants |
| Race (NIH/OMB) More than one race | 15 Participants | 39 Participants | 24 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 55 Participants | 51 Participants |
| Race (NIH/OMB) White | 60 Participants | 187 Participants | 127 Participants |
| Sex: Female, Male Female | 51 Participants | 164 Participants | 113 Participants |
| Sex: Female, Male Male | 51 Participants | 174 Participants | 123 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Rate of Patients With Actionable Alterations
An actionable alteration was defined as a cancer-associated genomic event for which there was a targeted drug available. Actionable genetic alterations were identified by a combination of standard-of-care cytogenetics/fluorescence in situ hybridization (FISH) and sequencing performed as part of the study. This study is considered feasible if at least 13% of participants analyzed have profile data and identifiable actionable alterations. A 90% exact binomial confidence interval is presented for the rate of patients with actionable alterations to compare the observed rate against 13%.
Time frame: Actionable alteration was identified based on a combination of fluorescence in situ hybridization (FISH)/cytogenetics and sequencing. Average time to full results was 2 weeks.
Population: The analysis dataset is comprised of the first 100 patients in Cohort 1, as defined per protocol. One patient in Cohort 2 was later identified to have relapsed/refractory disease, so therefore the analysis population contains 101 patients. The remainder of Cohort 1 patients and the entirety of Cohort 2 patients are represented in the analysis of secondary outcomes.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relapsed/Refractory Leukemia | Rate of Patients With Actionable Alterations | 77 percentage of participants |
Secondary
Analysis of Primary Leukemia Sensitivity Testing and Establishment of Xenograft Models
This Secondary Outcome will be addressed by completing analysis of the primary leukemia sensitivity testing to a panel of drugs or shRNA and establishing xenograft models in dedicated participating research laboratories and conducting co-clinical trials with the recommended matched therapy once the animal model is established.
Time frame: 2 Years
Secondary
Parent's Feelings and Understanding of Genomic Testing
This Secondary Outcome will be addressed by describing the hopes and concerns of parents of children with recurrent/refractory/high-risk de novo leukemia regarding genomic testing of their child's leukemia as well as their understanding of the testing and evaluate whether the hopes and concerns were realized following the return of results.
Time frame: 2 Years
Secondary
Rate of Results Reporting
This Secondary Outcome will be addressed by a description of the time of results reporting. Documentation of the time of sample receipt and processing, resources and personnel utilized at each step of the process, time to results reporting, interpretation and review by Expert panel and communication of results to the primary oncologist will be captured.
Time frame: 2 Years
Secondary
Rate of Somatic Genomic Alterations
This Secondary Outcome will be addressed by describing the somatic genomic alterations in Cohort 1 (Relapsed/Refractory Leukemia arm) and Cohort 2 (New Diagnosis arm) that are discovered by genomic analyses.
Time frame: 2 Years