Matched Targeted Therapy For High-Risk Leukemias and Myelodysplastic Syndrome

• ClinicalTrials.gov Identifier: NCT02670525
• Recruitment Status: Active, not recruiting
• First Posted: February 1, 2016
• Results First Posted: July 18, 2023
• Last Update Posted: May 8, 2024
• Sponsor: Dana-Farber Cancer Institute
• Information provided by (Responsible Party): Yana Pikman, MD, Dana-Farber Cancer Institute

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Diagnostic
• Conditions: Recurrent, Refractory, or High Risk Leukemias; Matched Targeted Therapy
• Intervention: Genetic: Leukemia Profiling
• Enrollment: 338

Participant Flow

Recruitment Details	Patients enrolled from August 17, 2016 to May 4, 2022.
Pre-assignment Details

Arm/Group Title	Relapsed/Refractory Leukemia	New Diagnosis
Arm/Group Description	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 (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
Period Title: Overall Study
Started	236	102
Matched Targeted Therapy (MTT) Data Available	157	74
Evaluable for Primary Endpoint	101	0 [1]
Completed [2]	14	9
Not Completed	222	93
Reason Not Completed
Death	94	14
Lost to Follow-up	4	1
Subject withdrew consent	1	0
Unknown, data entry delayed	123	78
[1] Only Cohort 1 is meant to address the primary outcome. Cohort 2 will be reported for secondary outcomes.; [2] A patient is completed if they completed the required follow-up and came off study.

Baseline Characteristics

Arm/Group Title		Relapsed/Refractory Leukemia	New Diagnosis	Total
Arm/Group Description		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.	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.	Total of all reporting groups
Overall Number of Baseline Participants		236	102	338
Baseline Analysis Population Description		This analysis dataset is comprised of all enrolled patients.
Age, Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	236 participants	102 participants	338 participants
		11.3; (0.5 to 28.7)	10.2; (0.4 to 26.5)	11.1; (0.4 to 28.7)
Age, Customized; Measure Type: Count of Participants; Unit of measure: Participants
Age (years) at sample	Number Analyzed	236 participants	102 participants	338 participants
	<1 years	7 3.0%	10 9.8%	17 5.0%
	1-9 years	91 38.6%	40 39.2%	131 38.8%
	10-17 years	94 39.8%	33 32.4%	127 37.6%
	>=18 years	44 18.6%	19 18.6%	63 18.6%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	236 participants	102 participants	338 participants
	Female	113 47.9%	51 50.0%	164 48.5%
	Male	123 52.1%	51 50.0%	174 51.5%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	236 participants	102 participants	338 participants
	Hispanic or Latino	43 18.2%	16 15.7%	59 17.5%
	Not Hispanic or Latino	144 61.0%	75 73.5%	219 64.8%
	Unknown or Not Reported	49 20.8%	11 10.8%	60 17.8%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	236 participants	102 participants	338 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	15 6.4%	9 8.8%	24 7.1%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	19 8.1%	14 13.7%	33 9.8%
	White	127 53.8%	60 58.8%	187 55.3%
	More than one race	24 10.2%	15 14.7%	39 11.5%
	Unknown or Not Reported	51 21.6%	4 3.9%	55 16.3%
Disease; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	236 participants	102 participants	338 participants
AML		89 37.7%	70 68.6%	159 47.0%
MDS		4 1.7%	2 2.0%	6 1.8%
JMML		2 0.8%	2 2.0%	4 1.2%
B-cell ALL		111 47.0%	1 1.0%	112 33.1%
T-cell ALL		14 5.9%	2 2.0%	16 4.7%
Infant MLL rearranged ALL		2 0.8%	4 3.9%	6 1.8%
Leukemia of ambiguous lineage		8 3.4%	8 7.8%	16 4.7%
Other rare leukemia		2 0.8%	4 3.9%	6 1.8%
Secondary leukemia		4 1.7%	9 8.8%	13 3.8%

Outcome Measures

1. Primary Outcome

Title	Rate of Patients With Actionable Alterations
Description	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.

Outcome Measure Data

Analysis Population Description

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/Group Title	Relapsed/Refractory Leukemia	New Diagnosis
Arm/Group Description:	Cohort 1: Relapsed/refractory leukemia; Acute lymphoblastic leukemia, first or greater relapse; Acute myeloid leukemia, 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.	Cohort 2: New diagnosis; Acute myeloid leukemia, new diagnosis (excluding acute promyelocytic leukemia (APL)); New diagnosis infant MLL-rearranged ALL or low hypodiploid (<40 chromosomes) ALL; Rare leukemia- e.g., 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.
Overall Number of Participants Analyzed	101	0
Measure Type: Number; Number (90% Confidence Interval); Unit of Measure: percentage of participants
	77; (69 to 84)

2. Secondary Outcome

Title	Rate of Somatic Genomic Alterations
Description	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

Outcome Measure Data Not Reported

3. Secondary Outcome

Title	Rate of Results Reporting
Description	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

Outcome Measure Data Not Reported

4. Secondary Outcome

Title	Parent's Feelings and Understanding of Genomic Testing
Description	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

Outcome Measure Data Not Reported

5. Secondary Outcome

Title	Analysis of Primary Leukemia Sensitivity Testing and Establishment of Xenograft Models
Description	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

Outcome Measure Data Not Reported

Adverse Events

Time Frame	Adverse event data was not of interest or collected for this study since there was no treatment intervention involved. Mortality data was not monitored for the duration of study completion, and cause of death was not collected for patients for whom a status of death was provided by outside sites.
Adverse Event Reporting Description	Adverse event data was not of interest or collected for this study since there was no treatment intervention involved. Mortality data was not monitored for the duration of study completion, and cause of death was not collected for patients for whom a status of death was provided by outside sites.
Arm/Group Title	Relapsed/Refractory Leukemia	New Diagnosis
Arm/Group Description	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.	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.
All-Cause Mortality
	Relapsed/Refractory Leukemia	New Diagnosis
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/0	0/0
Serious Adverse Events
	Relapsed/Refractory Leukemia	New Diagnosis
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/0	0/0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Relapsed/Refractory Leukemia	New Diagnosis
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/0	0/0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Dr. Yana Pikman
• Organization: Dana-Farber Cancer Institute
• Phone: 6176324754
• EMail: yana_pikman@dfci.harvard.edu

• Responsible Party: Yana Pikman, MD, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT02670525
• Other Study ID Numbers: 15-384
• First Submitted: January 28, 2016
• First Posted: February 1, 2016
• Results First Submitted: May 15, 2023
• Results First Posted: July 18, 2023
• Last Update Posted: May 8, 2024