Bortezomib and Combination Chemotherapy in Treating Younger Patients With Recurrent, Refractory, or Secondary Acute Myeloid Leukemia

NCT00666588 | Completed Phase 2 Results DMC

• 4 other identifiers: NCI-2009-00323U10CA098543CDR0000594224COG-AAML07P1
• Study Type: interventional
• Target: 52
• Locations: 3 countries
• Sites: 82

Brief Summary

This phase II trial is studying the side effects and best dose of bortezomib and to see how well it works when given together with combination chemotherapy in treating younger patients with recurrent, refractory, or secondary acute myeloid leukemia (AML). Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as idarubicin, cytarabine, and etoposide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) together with bortezomib may kill more cancer cells

Conditions

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 t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myelomonocytic Leukemia (M4); Childhood Acute Basophilic Leukemia; Childhood Acute Eosinophilic Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• Dose Limiting Toxicity

  Number of participants with dose limiting toxicity.

  During Course 1

• Overall Response (Complete Remission [CR] and CR With Partial Recovery [CRp]) During Course 1

  Overall response (complete remission \[CR\] and CR with partial recovery \[CRp\]) during course 1.

  After course 1

Secondary Outcomes (4)

• NF-kB Activity by Enzyme-linked Immunosorbent Assay (ELISA)

  At baseline, prior to and up to 24 hours after bortezomib treatment

• Proteasome Inhibition Activity

  At baseline

• Protein Expression Assessed by Western Blot

  At baseline, prior to and up to 24 hours after bortezomib treatment

• Feasibility of Stem Cell Quantitation: Percentage of Leukemia Initiation Cells (LIC) Depletion

  At baseline and after completion of course 1

Study Arms (4)

Bortezomib 1.3mg/m2-assess efficacy-low anthracycline exposure

EXPERIMENTAL

Bortezomib 1.3mg/m2 to assess efficacy in low prior anthracycline exposure. Patients receive idarubicin IV (12 mg/m2/day) over 15 minutes on days 1-3, low-dose cytarabine IV (100 mg/m2/day) continuously over days 1-7, and bortezomib IV (1.3 mg/m2) on days 1, 4, and 8. All patients receive intrathecal cytarabine (30 mg - age 1-1.99 years, 50 mg - age 2-2.99 years, 70 mg - age ≥ 3 years) prior to courses 1 and 2. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity (closed as of 08/01/10). Dosage modification based on age \< 3 years old.

Drug: idarubicin; Drug: cytarabine; Drug: bortezomib; Other: laboratory biomarker analysis

Bortezomib 1.0mg/m2-assess feasibility high anthracycline exp

EXPERIMENTAL

Bortezomib 1.0 mg/m2 to assess feasibility in high prior anthracycline exposure. Patients receive etoposide IV (150 mg/m2/dose) over 1 hour on days 1-5, high-dose cytarabine IV (1000 mg/m2/dose) over 1 hour twice daily on days 1-5, and bortezomib IV (1.0 mg/m2) on days 1, 4, and 8. All patients receive intrathecal cytarabine (30 mg - age 1-1.99 years, 50 mg - age 2-2.99 years, 70 mg - age ≥ 3 years) prior to courses 1 and 2. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.

Drug: cytarabine; Drug: bortezomib; Drug: etoposide; Other: laboratory biomarker analysis

Bortezomib 1.3 mg/m2-assess feasibility high anthracycline exp

EXPERIMENTAL

Bortezomib 1.3 mg/m2 to assess feasibility in high prior anthracycline exposure. Patients receive etoposide IV (150 mg/m2/dose) over 1 hour on days 1-5, high-dose cytarabine IV (1000 mg/m2/dose) over 1 hour twice daily on days 1-5, and bortezomib IV (1.3 mg/m2) on days 1, 4, and 8. All patients receive intrathecal cytarabine (30 mg - age 1-1.99 years, 50 mg - age 2-2.99 years, 70 mg - age ≥ 3 years) prior to courses 1 and 2. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity (dose-finding phase closed as of 10/10).

Drug: cytarabine; Drug: bortezomib; Drug: etoposide; Other: laboratory biomarker analysis

Bortezomib 1.3 mg/m2-assess efficacy high anthracycline exp

EXPERIMENTAL

Bortezomib 1.3 mg/m2 to assess efficacy in high prior anthracycline exposure. Patients receive etoposide IV (150 mg/m2/dose) over 1 hour on days 1-5, high-dose cytarabine IV (1000 mg/m2/dose) over 1 hour twice daily on days 1-5, and bortezomib IV (1.3 mg/m2) on days 1, 4, and 8. All patients receive intrathecal cytarabine (30 mg - age 1-1.99 years, 50 mg - age 2-2.99 years, 70 mg - age ≥ 3 years) prior to courses 1 and 2. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity

Drug: cytarabine; Drug: bortezomib; Drug: etoposide; Other: laboratory biomarker analysis

Interventions

idarubicin DRUG

Given IV

Also known as: 4-demethoxydaunorubicin, 4-DMDR, DMDR, IDA

Bortezomib 1.3mg/m2-assess efficacy-low anthracycline exposure

cytarabine DRUG

Given IV or IT

Also known as: ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U, cytosine arabinoside

Bortezomib 1.0mg/m2-assess feasibility high anthracycline exp; Bortezomib 1.3 mg/m2-assess efficacy high anthracycline exp; Bortezomib 1.3 mg/m2-assess feasibility high anthracycline exp; Bortezomib 1.3mg/m2-assess efficacy-low anthracycline exposure

bortezomib DRUG

Given IV

Also known as: LDP 341, MLN341, VELCADE

Bortezomib 1.0mg/m2-assess feasibility high anthracycline exp; Bortezomib 1.3 mg/m2-assess efficacy high anthracycline exp; Bortezomib 1.3 mg/m2-assess feasibility high anthracycline exp; Bortezomib 1.3mg/m2-assess efficacy-low anthracycline exposure

etoposide DRUG

Given IV

Also known as: EPEG, VP-16, VP-16-213

Bortezomib 1.0mg/m2-assess feasibility high anthracycline exp; Bortezomib 1.3 mg/m2-assess efficacy high anthracycline exp; Bortezomib 1.3 mg/m2-assess feasibility high anthracycline exp

laboratory biomarker analysis OTHER

Correlative studies

Bortezomib 1.0mg/m2-assess feasibility high anthracycline exp; Bortezomib 1.3 mg/m2-assess efficacy high anthracycline exp; Bortezomib 1.3 mg/m2-assess feasibility high anthracycline exp; Bortezomib 1.3mg/m2-assess efficacy-low anthracycline exposure

Eligibility Criteria

• Age: 1 Year - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis of acute myeloid leukemia (AML) according to WHO classification
• At least 5% blasts in the bone marrow
• With or without extramedullary disease
• To be eligible for the dose-finding phase (closed as of 10/10) :
• Relapsed patients must meet the following criteria:
• Must have had a prior diagnosis of AML, but may NOT have inv(16) or t(8;21) cytogenetics
• May be in first or any subsequent relapse
• If in first relapse, remission duration must be less than one year
• Refractory patients must meet the following criteria:
• Must have had a prior diagnosis of AML
• May have received one or more attempt at remission induction
• Patients with treatment-related AML may be previously treated or untreated for secondary AML
• To be eligible for the efficacy phase:
• Relapsed patients must meet the following criteria:
• Must have had a prior diagnosis of AML, with no restriction on prior cytogenetics

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (82)

University of Alabama at Birmingham

Birmingham, Alabama, 35293, United States

Location

Phoenix Childrens Hospital

Phoenix, Arizona, 85016, United States

Location

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Southern California Permanente Medical Group

Downey, California, 90242, United States

Location

Miller Children's Hospital

Long Beach, California, 90806, United States

Location

Children's Hospital and Research Center at Oakland

Oakland, California, 94609-1809, United States

Location

Childrens Hospital of Orange County

Orange, California, 92868-3874, United States

Location

Packard Children's Hospital Stanford University

Palo Alto, California, 94304, United States

Location

University of California San Francisco Medical Center

San Francisco, California, 94143, United States

Location

Connecticut Children's Medical Center

Hartford, Connecticut, 06106, United States

Location

Alfred I duPont Hospital for Children

Wilmington, Delaware, 19803, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Broward General Medical Center

Fort Lauderdale, Florida, 33316, United States

Location

Lee Memorial Health System

Fort Myers, Florida, 33901, United States

Location

Nemours Children's Clinic - Jacksonville

Jacksonville, Florida, 32207-8426, United States

Location

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136, United States

Location

Nemours Childrens Clinic - Orlando

Orlando, Florida, 32806, United States

Location

Nemours Children's Clinic - Pensacola

Pensacola, Florida, 32504, United States

Location

All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

Saint Joseph Children's Hospital of Tampa

Tampa, Florida, 33607, United States

Location

Children's Healthcare of Atlanta - Egleston

Atlanta, Georgia, 30322, United States

Location

Memorial Health University Medical Center

Savannah, Georgia, 31403, United States

Location

University of Hawaii

Honolulu, Hawaii, 96813, United States

Location

Childrens Memorial Hospital

Chicago, Illinois, 60614, United States

Location

Southern Illinois University

Springfield, Illinois, 62702, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Tulane University Health Sciences Center

New Orleans, Louisiana, 70112, United States

Location

Sinai Hospital of Baltimore

Baltimore, Maryland, 21215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

C S Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

Michigan State University - Breslin Cancer Center

East Lansing, Michigan, 48824-1313, United States

Location

Helen DeVos Children's Hospital at Spectrum Health

Grand Rapids, Michigan, 49503, United States

Location

Children's Hospitals and Clinics of Minnesota - Minneapolis

Minneapolis, Minnesota, 55404, United States

Location

University of Minnesota Medical Center-Fairview

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

The Childrens Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198-7830, United States

Location

Nevada Cancer Research Foundation CCOP

Las Vegas, Nevada, 89106, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

UMDNJ - Robert Wood Johnson University Hospital

New Brunswick, New Jersey, 08903, United States

Location

Newark Beth Israel Medical Center

Newark, New Jersey, 07112, United States

Location

Overlook Hospital

Summit, New Jersey, 07902, United States

Location

University of New Mexico

Albuquerque, New Mexico, 87106, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

State University of New York Upstate Medical University

Syracuse, New York, 13210, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Carolinas Medical Center

Charlotte, North Carolina, 28203, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Children's Hospital Medical Center of Akron

Akron, Ohio, 44308, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Rainbow Babies and Childrens Hospital

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

The Children's Medical Center of Dayton

Dayton, Ohio, 45404, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Legacy Emanuel Hospital and Health Center

Portland, Oregon, 97227, United States

Location

Penn State Hershey Children's Hospital

Hershey, Pennsylvania, 17033, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Childrens Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Palmetto Health Richland

Columbia, South Carolina, 29203, United States

Location

Sanford University of South Dakota Medical Center

Sioux Falls, South Dakota, 57117-5134, United States

Location

East Tennessee Childrens Hospital

Knoxville, Tennessee, 37916, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Driscoll Children's Hospital

Corpus Christi, Texas, 78411, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Texas Health Science Center

San Antonio, Texas, 78229-3900, United States

Location

Primary Children's Medical Center

Salt Lake City, Utah, 84113, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Saint Vincent Hospital

Green Bay, Wisconsin, 54301, United States

Location

Marshfield Clinic

Marshfield, Wisconsin, 54449, United States

Location

Midwest Children's Cancer Center

Milwaukee, Wisconsin, 53226, United States

Location

Princess Margaret Hospital for Children

Perth, Western Australia, 6008, Australia

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

IWK Health Centre

Halifax, Nova Scotia, B3J 3G9, Canada

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Hospital Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada

Location

MeSH Terms

Conditions

Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Congenital Abnormalities; Leukemia, Myelomonocytic, Acute; Leukemia, Eosinophilic, Acute

Interventions

Idarubicin; Cytarabine; Bortezomib; Etoposide

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides

Limitations and Caveats

The secondary outcome measure "Protein Expression Assessed by Western Blot" will never be reported as the investigators decided not to perform quantitative biologic analysis.

Results Point of Contact

• Title: Results Reporting Coordinator
• Organization: Children's Oncology Group

resultsreportingcoordinator@childrensoncologygroup.org

626-447-0064

Study Officials

• Jeffrey Moscow

  Children's Oncology Group

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2008
• First Posted: April 25, 2008
• Study Start: April 1, 2008
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: May 22, 2018
• Results First Posted: February 6, 2014

Record last verified: 2018-05

Locations

US (77); CA (4); AU (1)