Treatment for Relapsed/Refractory AML Based on a High Throughput Drug Sensitivity Assay

• Sponsor: University of Washington (Other)
• Overall Status: Completed
• CT.gov ID: NCT01872819
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 16
• Location: 1
• Arm: 1
• Actual Duration (Months): 15.5
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

This clinical trial uses a laboratory test called a high throughput sensitivity assay in planning treatment for patients with relapsed or refractory acute myeloid leukemia. The aim is to try to identify drugs that may be effective in killing leukemia cells for those patients who will not be cured with conventional chemotherapy. This assay will test multiple drugs simultaneously against a patient's own donated blood sample. The goal is to use this laboratory assay to best match a drug to a patient's disease.

Condition or Disease	Intervention/Treatment	Phase
Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Chronic Myelomonocytic Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts	Other: antitumor drug screening assay; Drug: chemotherapy; Biological: biological therapy	N/A

Detailed Description

PRIMARY OBJECTIVES:

1. To obtain results from a high throughput drug sensitivity assay within 10 days, procure drug within 14 days and initiate treatment within 21 days.

SECONDARY OBJECTIVES:

1. To achieve a response (cytoreduction or at least partial response) greater that than expected for comparable refractory patient populations with other salvage regimens.

OUTLINE:

A patient receives a drug intervention based on the results of a high throughput sensitivity assay. This assay best matches a drug to the patient's disease.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Treatment for Relapsed/Refractory AML Based on a High Throughput Drug Sensitivity Assay
• Actual Study Start Date: Aug 2, 2013
• Actual Primary Completion Date: Nov 1, 2014
• Actual Study Completion Date: Nov 17, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (chemotherapy, biological therapy) Patients receive 1 of 160 possible interventions based on high throughput drug sensitivity assay.	Other: antitumor drug screening assay; Undergo high throughput drug sensitivity assay; Other Names: antitumor drug screening assays drug screening assays, antitumor ; Drug: chemotherapy; Patients receive 1 of 160 possible interventions; Other Names: chemo ; Biological: biological therapy; Patients receive 1 of 160 possible interventions

Outcome Measures

Primary Outcome Measures

1. Achievability of Performing Individualized Drug Screening and Initiating Therapy Based on the Results of the Drug Screen for Poor Risk Patients With Relapsed or Refractory AML [Up to 21 days]

   Whether treatment was administered in the time frame based on the high throughput drug screen. Time from sample procurement to assay results.

Secondary Outcome Measures

1. Rate of Complete Response, Defined by Criteria of Cheson et al. [Baseline up to 2 years]

   Number of patients who achieved a Complete Response (CR) with Minimal Residual Disease (MRD), a Complete Response with incomplete hematologic recovery (CRi), or showed reduced blasts in their bone marrow by flow cytometry (Cytoreduction). Cheson et al. defines a CR as: Bone Marrow blasts <5%, absence of circulating blasts and blasts with Auer rods, absence of extramedullary disease, absolute neutrophil count >1.0 x 10^9/L, and platelet count >100 x 10^9/L. Cheson et al. defines a CRi as: all CR criteria except for residual neutropenia (<1.0 x 10^9/L) or thrombocytopenia (<100 x 10^9/L).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of acute myeloid leukemia by World Health Organization (WHO) criteria (except acute promyelocytic leukemia), acute leukemias of ambiguous lineage by WHO criteria, or myelodysplastic syndrome refractory anemia with excess blasts (RAEB)-2 by WHO classification or advanced myeloproliferative neoplasm with >= 10% blasts in the bone marrow or peripheral blood, including chronic myelomonocytic leukemia (CMML)-2 by WHO classification who have failed 2 inductions at initial diagnosis or failed >= 2 salvage regimens for relapsed acute myeloid leukemia (AML)

• Patients who have had a 1st remission for >= 1 year must have received cytotoxic chemotherapy as a salvage regimen

• Eastern Cooperative Oncology Group (ECOG) performance status 0 - 3

• Expectation that we can obtain about 100 million blasts from blood and/or marrow (for example, circulating blast count of 5,000 or greater)

• Bilirubin =< 1.5 x institutional upper limit of normal (IULN) 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 pyruvate glutamate transaminase (SPGT) (alanine aminotransferase [ALT]) =< 2.5 x IULN, unless elevation in thought to be due to hepatic infiltration by the hematologic malignancy

• Alkaline phosphatase =< 2.5 X ULN

• Serum creatinine =< 2.0 mg/dL

• Stable or improving on appropriate antimicrobial therapy for infection, without ongoing fever

• Informed consent

• Willing to use contraception

Exclusion Criteria:

• No other concomitant treatment for leukemia

• No other active cancer that requires systemic chemotherapy or radiation

• Significant organ compromise that will increase risk of toxicity or mortality

• Pregnancy or lactation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington	United States	98109

Sponsors and Collaborators

• University of Washington
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Pamela Becker, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Pamela S Becker, Principal Investigator, University of Washington
• ClinicalTrials.gov Identifier: NCT01872819
• Other Study ID Numbers: 8003; NCI-2013-01070; 8003; P30CA015704
• First Posted: Jun 7, 2013
• Last Update Posted: Jul 11, 2018
• Last Verified: Jun 1, 2018

• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Acute; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Leukemia, Monocytic, Acute; Leukemia, Megakaryoblastic, Acute; Leukemia, Erythroblastic, Acute; Myelodysplastic Syndromes; Myeloproliferative Disorders; Anemia, Refractory; Myelodysplastic-Myeloproliferative Diseases; Anemia, Refractory, with Excess of Blasts; Antineoplastic Agents

Study Results

Participant Flow

Arm/Group Title	Treatment (Chemotherapy, Biological Therapy)
Arm/Group Description	Patients receive 1 of 160 possible interventions based on high throughput drug sensitivity assay. antitumor drug screening assay: Undergo high throughput drug sensitivity assay chemotherapy: Patients receive 1 of 160 possible interventions biological therapy: Patients receive 1 of 160 possible interventions 16 patients were enrolled. 14 patients were treated.
Period Title: Overall Study
STARTED	14
COMPLETED	14
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (Chemotherapy, Biological Therapy)
Arm/Group Description	Patients receive 1 of 160 possible interventions based on high throughput drug sensitivity assay. antitumor drug screening assay: Undergo high throughput drug sensitivity assay chemotherapy: Patients receive 1 of 160 possible interventions biological therapy: Patients receive 1 of 160 possible interventions
Overall Participants	16
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	10 62.5%
>=65 years	6 37.5%
Sex: Female, Male (Count of Participants)
Female	6 37.5%
Male	10 62.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	16 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	2 12.5%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	14 87.5%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	16 100%

Outcome Measures

1. Primary Outcome

Title	Achievability of Performing Individualized Drug Screening and Initiating Therapy Based on the Results of the Drug Screen for Poor Risk Patients With Relapsed or Refractory AML
Description	Whether treatment was administered in the time frame based on the high throughput drug screen. Time from sample procurement to assay results.
Time Frame	Up to 21 days

Outcome Measure Data

Analysis Population Description

14 patients were treated.

Arm/Group Title	Treated Patients
Arm/Group Description	14 patients were treated.
Measure Participants	14
Median (Full Range) [days]	5.1

2. Secondary Outcome

Title	Rate of Complete Response, Defined by Criteria of Cheson et al.
Description	Number of patients who achieved a Complete Response (CR) with Minimal Residual Disease (MRD), a Complete Response with incomplete hematologic recovery (CRi), or showed reduced blasts in their bone marrow by flow cytometry (Cytoreduction). Cheson et al. defines a CR as: Bone Marrow blasts <5%, absence of circulating blasts and blasts with Auer rods, absence of extramedullary disease, absolute neutrophil count >1.0 x 10^9/L, and platelet count >100 x 10^9/L. Cheson et al. defines a CRi as: all CR criteria except for residual neutropenia (<1.0 x 10^9/L) or thrombocytopenia (<100 x 10^9/L).
Time Frame	Baseline up to 2 years

Outcome Measure Data

Analysis Population Description

14 patients received therapy. Out of 14 patients treated, 9 were evaluable (4 patients died prior to D14-21 marrow and 1 patient refused the D14-21 marrow).

Arm/Group Title	Treated Patients
Arm/Group Description
Measure Participants	9
CR with MRD	1
CRi	2
Cytoreduction	6

Adverse Events

Time Frame	2 years
Adverse Event Reporting Description	Other [Not Including Serious] Adverse Events were not monitored/assessed.
Arm/Group Title	Treatment (Chemotherapy, Biological Therapy)
Arm/Group Description	Patients receive 1 of 160 possible interventions based on high throughput drug sensitivity assay. antitumor drug screening assay: Undergo high throughput drug sensitivity assay chemotherapy: Patients receive 1 of 160 possible interventions biological therapy: Patients receive 1 of 160 possible interventions
All Cause Mortality
	Treatment (Chemotherapy, Biological Therapy)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Chemotherapy, Biological Therapy)
	Affected / at Risk (%)	# Events
Total	11/14 (78.6%)
Blood and lymphatic system disorders
coagulopathy	1/14 (7.1%)	1
DIC	1/14 (7.1%)	1
Cardiac disorders
acute systolic heart failure	1/14 (7.1%)	1
cardiogenic shock	1/14 (7.1%)	1
systolic dysfunction	1/14 (7.1%)	1
cardiomyopathy	1/14 (7.1%)	1
Gastrointestinal disorders
mucositis	1/14 (7.1%)	2
worsening abdominal pain	1/14 (7.1%)	1
General disorders
LE edema	1/14 (7.1%)	1
refractory shock	1/14 (7.1%)	1
multiorgan failure	1/14 (7.1%)	1
Infections and infestations
pneumonia	1/14 (7.1%)	1
febrile neutropenia	5/14 (35.7%)	7
pneumonia	1/14 (7.1%)	1
febrile neutropenia	1/14 (7.1%)	1
bacteremia-GPC	1/14 (7.1%)	1
sepsis	1/14 (7.1%)	1
c-diff colitis infection	1/14 (7.1%)	1
sepsis	1/14 (7.1%)	1
Lung infection - pulmonary aspergillosis	1/14 (7.1%)	1
skin infection - R leg cellulitis w/ abscess	1/14 (7.1%)	1
Lung infection - Stenotrophomonas bacteremia	1/14 (7.1%)	1
primary stenotrophomonas secondary AML	1/14 (7.1%)	1
Investigations
hypokalemia	2/14 (14.3%)	2
hyperbilirubinemia	2/14 (14.3%)	2
Hypoalbuminemia	1/14 (7.1%)	1
Alanine aminotransferase increased	1/14 (7.1%)	1
blood bilirubin increased	1/14 (7.1%)	1
Elevated AST	1/14 (7.1%)	1
Metabolism and nutrition disorders
Hyperglycemia	1/14 (7.1%)	1
hypoalbuminemia	1/14 (7.1%)	1
hypophosphatemia	1/14 (7.1%)	1
hypokalemia	1/14 (7.1%)	1
tumor lysis syndrome	2/14 (14.3%)	2
uric acid	1/14 (7.1%)	1
Musculoskeletal and connective tissue disorders
severe bone pain	1/14 (7.1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
malignant neoplasm progression	1/14 (7.1%)	1
Nervous system disorders
seizure	2/14 (14.3%)	2
headache	1/14 (7.1%)	1
Psychiatric disorders
confusion	1/14 (7.1%)	1
Respiratory, thoracic and mediastinal disorders
pleural effusions	1/14 (7.1%)	1
hypoxia	1/14 (7.1%)	1
hypoxemic respiratory failure	1/14 (7.1%)	1
hypoxia	1/14 (7.1%)	1
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysesthesia syndrome	1/14 (7.1%)	1
drug rash	1/14 (7.1%)	1
Vascular disorders
hypotension	2/14 (14.3%)	2
refractory hypotension	1/14 (7.1%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Chemotherapy, Biological Therapy)
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)

Limitations/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.