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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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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

Intervention / Treatment
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* Other: antitumor drug screening assay
* Drug: chemotherapy
* Biological: biological therapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (chemotherapy, biological therapy)<br>Patients receive 1 of 160 possible interventions based on high throughput drug sensitivity assay. | Other: antitumor drug screening assay<br>* Undergo high throughput drug sensitivity assay<br>* Other names: drug screening assays, antitumor;Drug: chemotherapy<br>* Patients receive 1 of 160 possible interventions<br>* Other names: chemo;Biological: biological therapy<br>* Patients receive 1 of 160 possible interventions<br>|

What is the study measuring?
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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 |