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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Myelomonocytic Leukemia; Recurrent Adult Acute Myeloid Leukemia; 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); Previously Treated Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Refractory Anemia With Excess Blasts
• Intervention / Treatment: Other: antitumor drug screening assay; Drug: chemotherapy; Biological: biological therapy

Detailed Description

PRIMARY OBJECTIVES:

I. 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:

I. 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 Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Whether treatment was administered in the time frame based on the high throughput drug screen. Time from sample procurement to assay results.	Up to 21 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Complete Response, Defined by Criteria of Cheson et al.	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).	Baseline up to 2 years

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start (Actual): August 2, 2013
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 17, 2014

Study Registration Dates

• First Submitted: June 4, 2013
• First Submitted That Met QC Criteria: June 4, 2013
• First Posted (Estimate): June 7, 2013

Study Record Updates

• Last Update Posted (Actual): July 11, 2018
• Last Update Submitted That Met QC Criteria: June 13, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Anemia; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Acute; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Leukemia, Monocytic, Acute; Leukemia, Megakaryoblastic, Acute; Leukemia, Erythroblastic, Acute; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Anemia, Refractory, with Excess of Blasts; Anemia, Refractory; Antineoplastic Agents
• Other Study ID Numbers: 8003 (Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium); P30CA015704 (U.S. NIH Grant/Contract); NCI-2013-01070 (Registry Identifier: CTRP (Clinical Trial Reporting Program))