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High Throughput Drug Sensitivity Assay and Genomics- Guided Treatment of Patients With Relapsed or Refractory Acute Leukemia

Primary Purpose

Recurrent Acute Leukemia of Ambiguous Lineage, Recurrent Acute Lymphoblastic Leukemia, Recurrent Acute Myeloid Leukemia

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Chemosensitivity Assay
Cytology Specimen Collection Procedure
Gene Expression Analysis
Genetic Variation Analysis
In Vitro Sensitivity-Directed Chemotherapy
Sponsored by
University of Washington
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Acute Leukemia of Ambiguous Lineage

Eligibility Criteria

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

Inclusion Criteria:

  • Diagnosis of acute leukemia by World Health Organization (WHO) criteria (e.g.-acute myeloid leukemia, acute lymphoblastic leukemia, acute leukemia of ambiguous origin)

  • Either:

    • Relapsed after or refractory to prior treatment with at least two regimens or lines of treatment
    • Prior failure of at least one regimen or line of treatment, with poor cytogenetic or other risk factors, and ineligible for other clinical trials
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 - 3
  • Expectation that we can obtain about 10 million blasts from blood and/or marrow (e.g., circulating blast count of 5,000 or greater or cellular marrow with greater than or equal to 20% blasts)
  • Bilirubin =< 1.5 x upper limit of normal (ULN) unless elevation is thought to be due to Gilbert's syndrome, hemolysis, or hepatic infiltration by the hematologic malignancy
  • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamate pyruvate transaminase (SPGT) (alanine aminotransferase [ALT]) =< 2.5 x ULN, unless elevation is thought to be due to hepatic infiltration by the hematologic malignancy
  • Alkaline phosphatase =< 2.5 x ULN, unless elevation is thought to be due to hepatic infiltration by the hematologic malignancy
  • Serum creatinine =< 2.0 mg/dL
  • Informed consent
  • Willing to use contraception when appropriate
  • Expected survival is greater than 100 days

Exclusion Criteria:

  • No other active cancer that requires systemic chemotherapy or radiation
  • Active systemic fungal, bacterial, viral or other infection, unless disease is under treatment with antimicrobials and considered controlled in the opinion of the investigator
  • Significant organ compromise that will increase risk of toxicity or mortality
  • Pregnancy or lactation

Sites / Locations

  • Fred Hutch/University of Washington Cancer Consortium

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (chemosensitivity testing, chemotherapy)

Arm Description

Leukemia cells purified from blood or bone marrow samples are analyzed for sensitivity to individual drugs and drug combination and by next generation sequencing.

Outcomes

Primary Outcome Measures

Percentage of Patients we Are Able to Test and Initiate Treatment Within a 21 Day Period
The study will be considered successful (feasibility demonstrated) if it is possible to choose and initiate a combination drug regimen within 21 days in 9 out of 15 patients. With that outcome, there would be 90% confidence that the true feasibility rate is at least 40%.

Secondary Outcome Measures

Rate of Complete Remission
The secondary objective is to evaluate the response to the chosen therapy. Response will be evaluated using European LeukemiaNet Response Evaluation Criteria in AML (2010 version)
Survival
Disease free and overall survival data will be assessed by contacting the referring MD or the patient every three months for the first two years.

Full Information

First Posted
August 25, 2015
Last Updated
June 29, 2022
Sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT02551718
Brief Title
High Throughput Drug Sensitivity Assay and Genomics- Guided Treatment of Patients With Relapsed or Refractory Acute Leukemia
Official Title
Individualized Treatment for Relapsed/Refractory Acute Leukemia Based on Chemosensitivity and Genomics/Gene Expression Data
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Completed
Study Start Date
September 11, 2015 (Actual)
Primary Completion Date
June 19, 2020 (Actual)
Study Completion Date
May 13, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This pilot clinical trial studies the feasibility of choosing treatment based on a high throughput ex vivo drug sensitivity assay in combination with mutation analysis for patients with acute leukemia that has returned after a period of improvement (relapsed) or does not respond to treatment (refractory). A high throughput screening assay tests many different drugs individually or in combination that kill leukemia cells in tiny chambers at the same time. High throughput drug sensitivity assay and mutation analysis may help guide the choice most effective for an individual's acute leukemia.
Detailed Description
PRIMARY OBJECTIVES: I. To test patient cells in a high throughput assay against individual drugs and drug combinations within 21 days to enable optimal choice of drug combinations for therapy. II. To test gene expression that reveals activation of druggable pathways or mutations in genes that confer susceptibility to specific agents may also be considered in choice of treatment. SECONDARY OBJECTIVE: I. To evaluate the response to the chosen therapy. OUTLINE: Leukemia cells obtained from blood or bone marrow are analyzed for sensitivity to both individual drugs and drug combinations via high throughput chemotherapy sensitivity assay and next generation sequencing assays. Doctors will then recommend chemotherapy regimens based on the results. After completion of the chemotherapy regimen, patients are followed up at 2-4 weeks for response, and then every 3 months for 2 years for duration of response and survival.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Acute Leukemia of Ambiguous Lineage, Recurrent Acute Lymphoblastic Leukemia, Recurrent Acute Myeloid Leukemia, Refractory Acute Lymphoblastic Leukemia, Refractory Acute Myeloid Leukemia, Refractory Acute Leukemia of Ambiguous Lineage

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
34 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (chemosensitivity testing, chemotherapy)
Arm Type
Experimental
Arm Description
Leukemia cells purified from blood or bone marrow samples are analyzed for sensitivity to individual drugs and drug combination and by next generation sequencing.
Intervention Type
Other
Intervention Name(s)
Chemosensitivity Assay
Other Intervention Name(s)
Chemosensitivity Testing
Intervention Description
Lab test in which leukemia cells obtained from blood or bone marrow are tested for sensitivity to 115 drugs individually and in certain combinations
Intervention Type
Other
Intervention Name(s)
Cytology Specimen Collection Procedure
Other Intervention Name(s)
Cytologic Sampling
Intervention Description
Undergo blood or bone marrow collection
Intervention Type
Genetic
Intervention Name(s)
Gene Expression Analysis
Intervention Description
Analysis of leukemia cell genes to identify possible drug targets
Intervention Type
Genetic
Intervention Name(s)
Genetic Variation Analysis
Other Intervention Name(s)
Genetic Variation, GENVAR, mutation analysis
Intervention Description
Analysis of leukemia cell genes to identify possible drug targets
Intervention Type
Drug
Intervention Name(s)
In Vitro Sensitivity-Directed Chemotherapy
Intervention Description
Receive personalized chemotherapy with one or more of the following drugs: Afatinib Arsenic trioxide Axitinib Azacitidine Bexarotene Bortezomib Bosutinib Busulfan Cabazitaxel Cabozantinib Carfilzomib Ceritinib Cladribine Clofarabine Crizotinib Cytarabine HCl Dabrafenib Dasatinib Daunorubicin HCl Decitabine Erlotinib Etoposide Everolimus Fludarabine Gefitinib Gemcitabine HCl Hydroxyurea Imatinib Irinotecan Lapatinib Lomustine Melphalan Mercaptopurine Methotrexate Mitoxantrone Nelarabine Nilotinib Paclitaxel Pazopanib Pentostatin Ponatinib Pralatrexate Rapamycin Regorafenib Romidepsin Ruxolitinib Sorafenib Sunitinib Temsirolimus Thioguanine Topotecan HCl Trametinib Tretinoin
Primary Outcome Measure Information:
Title
Percentage of Patients we Are Able to Test and Initiate Treatment Within a 21 Day Period
Description
The study will be considered successful (feasibility demonstrated) if it is possible to choose and initiate a combination drug regimen within 21 days in 9 out of 15 patients. With that outcome, there would be 90% confidence that the true feasibility rate is at least 40%.
Time Frame
Up to 21 days
Secondary Outcome Measure Information:
Title
Rate of Complete Remission
Description
The secondary objective is to evaluate the response to the chosen therapy. Response will be evaluated using European LeukemiaNet Response Evaluation Criteria in AML (2010 version)
Time Frame
Up to 2 years
Title
Survival
Description
Disease free and overall survival data will be assessed by contacting the referring MD or the patient every three months for the first two years.
Time Frame
Up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of acute leukemia by World Health Organization (WHO) criteria (e.g.-acute myeloid leukemia, acute lymphoblastic leukemia, acute leukemia of ambiguous origin) Either: Relapsed after or refractory to prior treatment with at least two regimens or lines of treatment Prior failure of at least one regimen or line of treatment, with poor cytogenetic or other risk factors, and ineligible for other clinical trials Eastern Cooperative Oncology Group (ECOG) performance status 0 - 3 Expectation that we can obtain about 10 million blasts from blood and/or marrow (e.g., circulating blast count of 5,000 or greater or cellular marrow with greater than or equal to 20% blasts) Bilirubin =< 1.5 x upper limit of normal (ULN) unless elevation is thought to be due to Gilbert's syndrome, hemolysis, or hepatic infiltration by the hematologic malignancy Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamate pyruvate transaminase (SPGT) (alanine aminotransferase [ALT]) =< 2.5 x ULN, unless elevation is thought to be due to hepatic infiltration by the hematologic malignancy Alkaline phosphatase =< 2.5 x ULN, unless elevation is thought to be due to hepatic infiltration by the hematologic malignancy Serum creatinine =< 2.0 mg/dL Informed consent Willing to use contraception when appropriate Expected survival is greater than 100 days Exclusion Criteria: No other active cancer that requires systemic chemotherapy or radiation Active systemic fungal, bacterial, viral or other infection, unless disease is under treatment with antimicrobials and considered controlled in the opinion of the investigator Significant organ compromise that will increase risk of toxicity or mortality Pregnancy or lactation
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mary-Elizabeth Percival
Organizational Affiliation
Fred Hutch/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fred Hutch/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States

12. IPD Sharing Statement

Learn more about this trial

High Throughput Drug Sensitivity Assay and Genomics- Guided Treatment of Patients With Relapsed or Refractory Acute Leukemia

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