Liposome-encapsulated Daunorubicin-Cytarabine, Fludarabine Phosphate, Cytarabine, and Filgrastim in Treating Younger Patients With Relapsed or Refractory Acute Myeloid Leukemia

NCT02642965 | Completed Phase 1 Results

• 5 other identifiers: AAML1421NCI-2015-01917PAAML1421_R02PAPP01s16-00955U10CA180886
• Study Type: interventional
• Target: 38
• Locations: 2 countries
• Sites: 73

Brief Summary

This phase I/II trial studies the side effects and best dose of liposome-encapsulated daunorubicin-cytarabine when given with fludarabine phosphate, cytarabine, and filgrastim and to see how well they work in treating younger patients with acute myeloid leukemia that has come back after treatment (relapsed) or is not responding to treatment (is refractory). Liposome-encapsulated daunorubicin-cytarabine is made up of two chemotherapy drugs, cytarabine and daunorubicin hydrochloride, and works to stop cancer cell growth by blocking the cells from dividing. Drugs used in chemotherapy, such as fludarabine phosphate and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Filgrastim may increase the production of blood cells and may help the immune system recover from the side effects of chemotherapy. Giving liposome-encapsulated daunorubicin-cytarabine followed by fludarabine phosphate, cytarabine, and filgrastim may be a better treatment for patients with relapsed acute myeloid leukemia and may cause fewer side effects to the heart, a common effect of other chemotherapy treatments for acute myeloid leukemia.

Conditions

Acute Myeloid Leukemia Post Cytotoxic Therapy; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• Number of Participants With a Dose-limiting Toxicity

  Number of patients in the dose-finding phase with a dose-limiting toxicity, graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

  28 days

• Percentage of Responders (Complete Response or Complete Remission With Partial Platelet Recovery) After up to 2 Cycles

  Best response (complete response or complete remission with partial platelet recovery) after up to 2 cycles of therapy, where response is assessed using the revised Acute Myeloid Leukemia International Working Group Criteria. Percentage of responders is calculated using the methods of Jung and Kim. 90% confidence interval is determined using the methods of Koyama and Chen.

  Up to 8 weeks

Secondary Outcomes (9)

• Percentage of Responders (Complete Response or Complete Remission With Partial or Incomplete Platelet Recovery) After First Cycle of Therapy

  Up to 4 weeks

• Liposome-encapsulated Daunorubicin Clearance

  Prior to infusion on day 5 and, 45 and 90 minutes post day 5 infusion of cycle 1

• Liposome-encapsulated Daunorubicin Volume of Distribution

  Prior to infusion on day 5 and, 45 and 90 minutes post day 5 infusion of cycle 1

• Liposome-encapsulated Daunorubicin Time of Maximum Concentration

  Prior to infusion on day 5 and, 45 and 90 minutes post day 5 infusion of cycle 1

• Liposome-encapsulated Daunorubicin Area Under the Curve

  Prior to infusion on day 5 and, 45 and 90 minutes post day 5 infusion of cycle 1

Other Outcomes (9)

• Length of Hospitalization Time

  Up to 1 year

• Time to Bone Marrow Count Recovery

  Up to 1 year

• Time to Peripheral Blood Cell Count Recovery

  Up to 1 year

Study Arms (1)

Treatment (CPX-351 and FLAG)

EXPERIMENTAL

COURSE 1: Patients receive cytarabine IT on day 0 and at day 28-30 or up to 7 days prior to day 1 of course 2, and liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1, 3, and 5. Patients with CNS1 receive no further CNS-directed therapy in course 1. Patients with CNS2 disease may receive additional 4-6 doses of cytarabine IT twice weekly starting 48 hours after the third dose of liposome-encapsulated daunorubicin-cytarabine until CNS is clear at the discretion of the investigator. Patients meeting criteria for CR, CRp, and CRi may proceed to course 2. COURSE 2: Patients receive filgrastim on days 1-5 and then on day 15 until blood count recovery, and fludarabine phosphate IV over 30 minutes and high-dose cytarabine IV over 1-3 hours QD on days 1-5.

Drug: Cytarabine; Biological: Filgrastim; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Drug: Liposome-encapsulated Daunorubicin-Cytarabine; Other: Pharmacological Study

Interventions

Cytarabine DRUG

Given IT or IV

Also known as: .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-Cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453

Treatment (CPX-351 and FLAG)

Filgrastim BIOLOGICAL

Given SC or IV

Also known as: Filgrastim-aafi, Filgrastim-ayow, G-CSF, Neupogen, Nivestym, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor, Releuko, rG-CSF, Tevagrastim

Treatment (CPX-351 and FLAG)

Fludarabine Phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586

Treatment (CPX-351 and FLAG)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (CPX-351 and FLAG)

Liposome-encapsulated Daunorubicin-Cytarabine DRUG

Given IV

Also known as: CPX-351, Cytarabine-Daunorubicin Liposome for Injection, Daunorubicin and Cytarabine (Liposomal), Liposomal AraC-Daunorubicin CPX-351, Liposomal Cytarabine-Daunorubicin, Liposome-encapsulated Combination of Daunorubicin and Cytarabine, Vyxeos

Treatment (CPX-351 and FLAG)

Pharmacological Study OTHER

Correlative studies

Treatment (CPX-351 and FLAG)

Eligibility Criteria

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

You may qualify if:

• Patients must have had histologic verification of AML at original diagnosis
• Patient must have one of the following:
• Recurrent disease with \>= 5% blasts in the bone marrow (M2/M3 bone marrow), with or without extramedullary disease.
• Recurrent disease with an absolute blast count greater than 1,000 per microliter in the peripheral blood with or without extramedullary disease
• To be eligible for the dose-finding phase: (the dose-finding phase completed in 12/2016)
• Relapsed patients
• Patients must be in first relapse, and
• Patients must not have received prior re-induction therapy
• Refractory patients
• Patients must not have received more than one attempt at remission induction, which may consist of up to two different therapy courses; Children Oncology Group (COG) AAML1031 de novo therapy including induction I and induction II is an example
• Treatment-related AML (t-AML)
• Patients must be previously untreated for secondary AML
• To be eligible for the phase 2 efficacy phase:
• Relapse patients:
• Patients must be in first marrow relapse, and

You may not qualify if:

• Patients who have received \> 450 mg/m\^2 daunorubicin equivalents; patients who relapse after receiving AAML0531/AAML1031 therapy will be eligible for this study, provided they have not received any additional anthracyclines; NOTE: for the purposes of determining eligibility for this protocol, the following cardiotoxicity multipliers will be used to determine daunorubicin equivalents:
• Doxorubicin (doxorubicin hydrochloride): 1
• Mitoxantrone: 3
• Idarubicin: 3
• Epirubicin: 0.5
• Patients who are currently receiving another investigational drug
• Patients receiving medications for treatment of left ventricular systolic dysfunction
• Patients with any of the following diagnoses:
• Acute promyelocytic leukemia (APL)
• Down syndrome
• Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome
• Wilson's disease and any other disorder of copper metabolism
• Juvenile myelomonocytic leukemia (JMML)
• Patients with documented active, uncontrolled infection at the time of study entry
• Patients with known active hepatitis B virus (HBV) and hepatitis C virus (HCV) infections

Sponsors & Collaborators

• Children's Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (73)

Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

Location

Phoenix Childrens Hospital

Phoenix, Arizona, 85016, United States

Location

Arkansas Children's Hospital

Little Rock, Arkansas, 72202-3591, United States

Location

Kaiser Permanente Downey Medical Center

Downey, California, 90242, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

Loma Linda University Medical Center

Loma Linda, California, 92354, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Valley Children's Hospital

Madera, California, 93636, United States

Location

UCSF Benioff Children's Hospital Oakland

Oakland, California, 94609, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

UCSF Medical Center-Mission Bay

San Francisco, California, 94158, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, 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

University of Florida Health Science Center - Gainesville

Gainesville, Florida, 32610, United States

Location

Nemours Children's Clinic-Jacksonville

Jacksonville, Florida, 32207, United States

Location

Nemours Children's Clinic - Pensacola

Pensacola, Florida, 32504, United States

Location

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

Children's Healthcare of Atlanta - Egleston

Atlanta, Georgia, 30322, United States

Location

Lurie Children's Hospital-Chicago

Chicago, Illinois, 60611, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

Ascension Saint Vincent Indianapolis Hospital

Indianapolis, Indiana, 46260, United States

Location

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, 40536, United States

Location

Eastern Maine Medical Center

Bangor, Maine, 04401, United States

Location

Maine Children's Cancer Program

Scarborough, Maine, 04074, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

C S Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

Ascension Saint John Hospital

Detroit, Michigan, 48236, United States

Location

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Children's Mercy Hospitals and Clinics

Kansas City, Missouri, 64108, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Mercy Hospital Saint Louis

St Louis, Missouri, 63141, United States

Location

Children's Hospital and Medical Center of Omaha

Omaha, Nebraska, 68114, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

NYU Winthrop Hospital

Mineola, New York, 11501, United States

Location

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, 10016, United States

Location

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

State University of New York Upstate Medical University

Syracuse, New York, 13210, United States

Location

Mission Hospital

Asheville, North Carolina, 28801, 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

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Saint Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

The Children's Hospital at TriStar Centennial

Nashville, Tennessee, 37203, United States

Location

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, 75390, United States

Location

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, 77030, United States

Location

Children's Hospital of San Antonio

San Antonio, Texas, 78207, United States

Location

Primary Children's Hospital

Salt Lake City, Utah, 84113, United States

Location

University of Vermont and State Agricultural College

Burlington, Vermont, 05405, United States

Location

Children's Hospital of The King's Daughters

Norfolk, Virginia, 23507, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Providence Sacred Heart Medical Center and Children's Hospital

Spokane, Washington, 99204, United States

Location

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

Location

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

IWK Health Centre

Halifax, Nova Scotia, B3K 6R8, Canada

Location

Kingston Health Sciences Centre

Kingston, Ontario, K7L 2V7, Canada

Location

The Montreal Children's Hospital of the MUHC

Montreal, Quebec, H3H 1P3, Canada

Location

Centre Hospitalier Universitaire Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Centre Hospitalier Universitaire de Quebec

Québec, G1V 4G2, Canada

Location

Related Publications (1)

• Cooper TM, Absalon MJ, Alonzo TA, Gerbing RB, Leger KJ, Hirsch BA, Pollard J, Razzouk BI, Aplenc R, Kolb EA. Phase I/II Study of CPX-351 Followed by Fludarabine, Cytarabine, and Granulocyte-Colony Stimulating Factor for Children With Relapsed Acute Myeloid Leukemia: A Report From the Children's Oncology Group. J Clin Oncol. 2020 Jul 1;38(19):2170-2177. doi: 10.1200/JCO.19.03306. Epub 2020 May 13.

  PMID: 32401633 DERIVED

Related Links

• Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive

MeSH Terms

Interventions

Cytarabine; Filgrastim; Granulocyte Colony-Stimulating Factor; fludarabine phosphate; CPX-351; Injections; Daunorubicin; Liposomes

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Drug Administration Routes; Drug Therapy; Therapeutics; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Membranes, Artificial; Biomedical and Dental Materials; Drug Carriers; Dosage Forms; Pharmaceutical Preparations; Manufactured Materials; Technology, Industry, and Agriculture; Biomimetic Materials

Results Point of Contact

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

resultsreportingcoordinator@childrensoncologygroup.org

626-447-0064

Study Officials

• Todd M Cooper

  Children's Oncology Group

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2015
• First Posted: December 30, 2015
• Study Start: May 2, 2016
• Primary Completion: December 31, 2018
• Study Completion: June 30, 2023
• Last Updated: September 8, 2023
• Results First Posted: December 30, 2019

Record last verified: 2023-08

Locations

US (67); CA (6)