Targeted Therapy in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia or Acute Myelogenous Leukemia

NCT01620216 | Terminated Phase 2 Results DMC

• 4 other identifiers: IRB00007195NCI-2012-01084CA180-392R21CA159265
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well targeted therapy works in treating patients with acute lymphoblastic leukemia or acute myelogenous leukemia that has come back after a period of improvement or does not respond to treatment. Testing patients' blood or bone marrow to find out if their type of cancer may be sensitive to a specific drug may help doctors choose more effective treatments. Dasatinib, sunitinib malate, sorafenib tosylate, ponatinib hydrochloride, pacritinib, ruxolitinib, and idelalisib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving targeted therapy based on cancer type may be an effective treatment for acute lymphoblastic leukemia or acute myelogenous leukemia.

Conditions

Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Recurrent Acute Lymphoblastic Leukemia; Recurrent Acute Myeloid Leukemia; Refractory Acute Lymphoblastic Leukemia; Refractory Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Clinical Activity

  Will be defined as defined as a decrease of at least 25% in bone marrow blast counts or peripheral blood blast. The proportion of patients achieving the endpoint along with its 95% exact binomial confidence interval will be presented.

  Up to 28 days

Secondary Outcomes (4)

• Overall Objective Response Rates (Complete and Partial)

  Up to 3 years

• Progression-free Survival

  From the start of study drug treatment to death, regardless of cause of death, or date of disease progression defined as a >= 50% increase in leukemic bone marrow blasts, whichever occurs first, assessed up to 3 years

• Overall Survival

  From the date of subject registration to death, regardless of causes of death, assessed up to 3 years

• Clinical Activity

  Up to 28 days

Other Outcomes (1)

• Presence of Active/Aberrant Kinase Pathways

  Up to 3 years

Study Arms (7)

Group I (dasatinib)

EXPERIMENTAL

Patients receive dasatinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Other: Antitumor Drug Screening Assay; Drug: Dasatinib; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

Group II (sutinib malate)

EXPERIMENTAL

Patients receive sutinib malate PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Other: Antitumor Drug Screening Assay; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Sunitinib; Drug: Sunitinib Malate

Group III (sorafenib tosylate)

EXPERIMENTAL

Patients receive sorafenib tosylate PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Other: Antitumor Drug Screening Assay; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Sorafenib; Drug: Sorafenib Tosylate

Group IV (ponatinib hydrochloride)

EXPERIMENTAL

Patients receive ponatinib hydrochloride PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity

Other: Antitumor Drug Screening Assay; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Ponatinib; Drug: Ponatinib Hydrochloride

Group V (pacritinib)

EXPERIMENTAL

Patients receive pacritinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Other: Antitumor Drug Screening Assay; Other: Laboratory Biomarker Analysis; Drug: Pacritinib; Other: Pharmacological Study

Group VI (ruxolitinib)

EXPERIMENTAL

Patients receive ruxolitinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Other: Antitumor Drug Screening Assay; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Ruxolitinib

Group VII (idelalisib)

EXPERIMENTAL

Patients receive idelalisib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Other: Antitumor Drug Screening Assay; Drug: Idelalisib; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

Interventions

Antitumor Drug Screening Assay OTHER

Undergo pre clinical kinase inhibitor activity screening

Also known as: Drug Screening Assays, Antitumor

Group I (dasatinib); Group II (sutinib malate); Group III (sorafenib tosylate); Group IV (ponatinib hydrochloride); Group V (pacritinib); Group VI (ruxolitinib); Group VII (idelalisib)

Dasatinib DRUG

Given PO

Also known as: BMS-354825, Dasatinib Hydrate, Dasatinib Monohydrate, Sprycel

Group I (dasatinib)

Idelalisib DRUG

Given PO

Also known as: CAL-101, GS 1101, GS-1101, Phosphoinositide-3 Kinase Delta Inhibitor CAL-101, Zydelig

Group VII (idelalisib)

Laboratory Biomarker Analysis OTHER

Correlative studies

Group I (dasatinib); Group II (sutinib malate); Group III (sorafenib tosylate); Group IV (ponatinib hydrochloride); Group V (pacritinib); Group VI (ruxolitinib); Group VII (idelalisib)

Pacritinib DRUG

Given PO

Also known as: Oral JAK2 Inhibitor SB1518, SB 1518, SB-1518, SB1518

Group V (pacritinib)

Pharmacological Study OTHER

Correlative studies

Group I (dasatinib); Group II (sutinib malate); Group III (sorafenib tosylate); Group IV (ponatinib hydrochloride); Group V (pacritinib); Group VI (ruxolitinib); Group VII (idelalisib)

Ponatinib DRUG

Given PO

Also known as: AP-24534, AP24534

Group IV (ponatinib hydrochloride)

Ponatinib Hydrochloride DRUG

Given PO

Also known as: AP24534 HCl, Iclusig

Group IV (ponatinib hydrochloride)

Ruxolitinib DRUG

Given PO

Also known as: INCB-18424, INCB18424, Jakafi, Oral JAK Inhibitor INCB18424

Group VI (ruxolitinib)

Sorafenib DRUG

Given PO

Also known as: BA4 43 9006, BAY 43-9006, Bay-439006

Group III (sorafenib tosylate)

Sorafenib Tosylate DRUG

Given PO

Also known as: BAY 43-9006 Tosylate, BAY 54-9085, Nexavar, sorafenib

Group III (sorafenib tosylate)

Sunitinib DRUG

Given PO

Group II (sutinib malate)

Sunitinib Malate DRUG

Given PO

Also known as: SU011248, SU11248, sunitinib, Sutent

Group II (sutinib malate)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants \>= 18 years of age with relapsed/refractory leukemia with a confirmed diagnosis of acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL) who meet the following criteria:
• Individuals aged 18-64 years with salvage treatment failures only - defined as relapsed or refractory to after least 1 cycle of salvage therapy
• Given the clinical activity and use of hypomethylating agents in AML patients, initial and salvage therapy may include hypomethylating agents
• Age \>= 65 years: Refractory to induction chemotherapy - defined as no response to initial therapy or have relapsed after initial therapy
• Individuals aged \>= 65 years, with chronic myelomonocytic leukemia (CMML) or myelodysplasia (MDS) that transform to acute leukemia while actively receiving hypomethylating agents (i.e., decitabine or azacytidine) will be considered induction failures and are thus eligible for this trial; for Philadelphia positive (Ph+) ALL, initial therapy and salvage therapy may include steroids and imatinib or dasatinib
• Primary patient samples must show in vitro kinase inhibitor sensitivity as determined by the Oregon Health and Science University (OHSU) functional kinase inhibitor screen; for OHSU patients, functional kinase inhibitor screening may be performed as part of this study or through enrollment in eIRB4422 if the identical Food and Drug Administration (FDA)/Clinical Laboratory Improvement Act (CLIA) approved assay is used and a result is available within 2 weeks of starting on study drug treatment
• Patients must have normal organ function as defined below:
• Serum creatinine \< 2.0 x institutional upper limit of normal (ULN)
• International normalized ratio (INR) \< 1.5 x institutional ULN
• Adequate hepatic function as defined by the following criteria:
• Total serum bilirubin =\< 1.5 x ULN, unless due to Gilbert's syndrome
• Alanine aminotransferase (ALT) =\< 2.5 x ULN
• Aspartate aminotransferase (AST) =\< 2.5 x ULN
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• Discontinuation of anti-coagulants and anti-platelet drugs at least 7 days prior to start of study drug

You may not qualify if:

• Any leukemia treatment within 1 week (for cytotoxic therapy) and/or 5 half lives (for targeted agents) prior to starting study drug; corticosteroids are allowable throughout the study to treat concomitant medical disorders per provider discretion; hydroxyurea is allowed prior to enrollment and after the start of the study drug for the control of peripheral leukemic blasts in subjects with leukocytosis per physician discretion
• Recent uncontrolled angina, recent \> New York Heart Association (NYHA) class II congestive heart failure, or recent myocardial infarction (MI) within 6 months prior to start of study treatment
• Diagnosed congenital long QT syndrome
• Any recent history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes)
• History of clinically significant bleeding disorder unrelated to cancer
• Drugs that affect the cytochrome P450 family 3 subfamily A polypeptide 4 (CYP3A4) system (inducers/inhibitors/substrates) are allowed but should be used with caution depending on specific kinase inhibitor used; dietary supplements will be discouraged; however, their use may be allowed on a case by case basis per the discretion of the investigator after consultation with an oncology pharmacist
• Uncontrolled intercurrent illness that would limit compliance with study requirements
• Pregnant or lactating women are excluded from this study
• Known human immunodeficiency virus (HIV)-positive patients are excluded from the study
• History of hypersensitivity to any of the kinase inhibitors included in this study
• Dasatinib
• Known pulmonary arterial hypertension
• Patients may not have a clinically significant pleural or pericardial effusion
• Uncontrolled hypertension: inability to maintain blood pressure below the limit of 140/90 mmHg
• Any history of second or third degree heart block (may be eligible if the subject currently has a pacemaker)

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• National Cancer Institute (NCI): collaborator
• Oregon Health and Science University: collaborator

Study Sites (1)

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

MeSH Terms

Conditions

Leukemia, Myelomonocytic, Chronic; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute

Interventions

Drug Screening Assays, Antitumor; Dasatinib; idelalisib; 11-(2-pyrrolidin-1-ylethoxy)-14,19-dioxa-5,7,26-triazatetracyclo(19.3.1.1(2,6).1(8,12))heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene; ponatinib; ruxolitinib; Sorafenib; Sunitinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Drug Evaluation, Preclinical; Evaluation Studies as Topic; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Phenylurea Compounds; Urea; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines; Pyrroles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Dr. Stephen Spurgeon
• Organization: OHSU

spurgeos@ohsu.edu

5034948950

Study Officials

• Marc Loriaux

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 13, 2012
• First Posted: June 15, 2012
• Study Start: May 11, 2012
• Primary Completion: April 25, 2017
• Study Completion: April 30, 2017
• Last Updated: November 4, 2021
• Results First Posted: October 4, 2021

Record last verified: 2021-10

Locations

US (1)