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Matched Targeted Therapy For High-Risk Leukemias and Myelodysplastic Syndrome

Primary Purpose

Recurrent, Refractory, or High Risk Leukemias, Matched Targeted Therapy

Status
Active
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Leukemia Profiling
Sponsored by
Dana-Farber Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Recurrent, Refractory, or High Risk Leukemias focused on measuring Recurrent, Refractory, or High Risk Leukemias, Matched targeted therapy

Eligibility Criteria

undefined - 30 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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, 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

Cohort 2: New diagnosis

  • Acute myeloid leukemia, new diagnosis
  • 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

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.

Sites / Locations

  • UCSF Helen Diller Family Comprehensive Cancer Center
  • Children's Hospital Colorado
  • Children's Healthcare of Atlanta
  • The University of Chicago
  • Johns Hopkins Hospital
  • Dana Farber Cancer Institute
  • Children's Hospital's and Clinics of Minnesota
  • Washington University at St. Louis School of Medicine
  • The Children's Hospital at Montefiore
  • Roswell Park Comprehensive Cancer Center
  • Columbia University Medical Center
  • Memorial Sloan Kettering Cancer Center
  • Children's Hospital of Philadelphia
  • Seattle Children's Hospital
  • Children's Hospital of Wisconsin

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Relapsed/Refractory Leukemia

New Diagnosis

Arm 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.

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.

Outcomes

Primary Outcome Measures

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%.

Secondary Outcome Measures

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.
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.
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.
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.

Full Information

First Posted
January 28, 2016
Last Updated
July 20, 2023
Sponsor
Dana-Farber Cancer Institute
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1. Study Identification

Unique Protocol Identification Number
NCT02670525
Brief Title
Matched Targeted Therapy For High-Risk Leukemias and Myelodysplastic Syndrome
Official Title
Matched Targeted Therapy (MTT) Recommendation for Patients With Recurrent, Refractory, or High Risk Leukemias and Myelodysplastic Syndrome
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
August 17, 2016 (Actual)
Primary Completion Date
May 16, 2022 (Actual)
Study Completion Date
May 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Dana-Farber Cancer Institute

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent, Refractory, or High Risk Leukemias, Matched Targeted Therapy
Keywords
Recurrent, Refractory, or High Risk Leukemias, Matched targeted therapy

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
338 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Relapsed/Refractory Leukemia
Arm Type
Experimental
Arm 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.
Arm Title
New Diagnosis
Arm Type
Experimental
Arm Description
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.
Intervention Type
Genetic
Intervention Name(s)
Leukemia Profiling
Intervention Description
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.
Primary Outcome Measure Information:
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.
Secondary Outcome Measure Information:
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
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
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
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

10. Eligibility

Sex
All
Maximum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yana Pikman, MD
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
UCSF Helen Diller Family Comprehensive Cancer Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Children's Healthcare of Atlanta
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
The University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Johns Hopkins Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Children's Hospital's and Clinics of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55404
Country
United States
Facility Name
Washington University at St. Louis School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
The Children's Hospital at Montefiore
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Roswell Park Comprehensive Cancer Center
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19404
Country
United States
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Facility Name
Children's Hospital of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Matched Targeted Therapy For High-Risk Leukemias and Myelodysplastic Syndrome

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