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Trial record 1 of 1 for:    NCT01701323
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Laboratory-Treated Donor Cord Blood Cell Infusion Following Combination Chemotherapy in Treating Younger Patients With Relapsed or Refractory Acute Myeloid Leukemia

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01701323
First Posted: October 5, 2012
Last Update Posted: July 2, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
National Cancer Institute (NCI)
Seattle Children's Research Institute Center for Clinical and Translational Research
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
  Purpose
This pilot clinical trial studies infusion of laboratory-grown donor cord blood cells following combination chemotherapy in treating younger patients with acute myeloid leukemia that has returned or that does not respond to treatment. Chemotherapy drugs 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. Chemotherapy also kills healthy infection-fighting cells, increasing the risk of infection. The infusion of laboratory-grown cord blood cells may be able to replace blood-forming cells that were destroyed by chemotherapy. This may decrease the risk of infection following chemotherapy, and allow for more chemotherapy to be given so that more cancer cells are killed.

Condition Intervention
Acute Leukemia of Ambiguous Lineage Adult Acute Myeloid Leukemia in Remission Childhood Acute Myeloid Leukemia in Remission Recurrent Adult Acute Myeloid Leukemia Recurrent Childhood Acute Myeloid Leukemia Untreated Adult Acute Myeloid Leukemia Drug: Cytarabine Procedure: Ex Vivo-Expanded Cord Blood Progenitor Cell Infusion Biological: Filgrastim Drug: Fludarabine Phosphate

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Study Evaluating the Use of Ex Vivo Expanded Cord Blood Progenitors as Supportive Care Following Chemotherapy (FLAG) in Patients With AML or Acute Leukemia of Ambiguous Lineage

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Delayed marrow recovery [ Time Frame: After day 42 ]
    Defined as failure to achieve neutrophil recovery (absolute neutrophil count [ANC] > 500) by day 42 post treatment with marrow cellularity < 5% and marrow blast count < 5%.

  • Incidence of platelet refractoriness in the presence of alloimmunization as a direct result of ex vivo expanded cord blood product infusion [ Time Frame: Up to 2 years ]
    Will be defined by platelet count < 50K when platelet count is obtained 1 hour post platelet transfusion.

  • Occurrence of grade > 3 infusional toxicity with administration of ex vivo expanded cord blood therapy [ Time Frame: Up to 2 years ]
    Will be assessed according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0.

  • Occurrence of transfusion associated graft versus host disease [ Time Frame: Up to 2 years ]
    Will be evaluated.

  • Rates of treatment related mortality [ Time Frame: Up to 2 years ]
    Will be evaluated.


Secondary Outcome Measures:
  • In vivo persistence of ex vivo expanded cellular therapy [ Time Frame: Up to 2 years ]
    Will be assessed by peripheral blood cell sorted deoxyribonucleic acid (DNA) chimerisms of the cluster of differentiation myeloid and lymphoid cell lineages as well as whole marrow chimerisms.

  • Incidence of grade 3 or 4 infections [ Time Frame: Up to 2 years ]
    Will be assessed according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0 in the neutropenic period following fludarabine phosphate, cytarabine, and filgrastim (FLAG) administration.

  • Incidence of grade > 3 chemotherapy-related toxicity in the first 30 days following fludarabine phosphate, cytarabine, and filgrastim (FLAG) therapy [ Time Frame: Up to 30 days ]
    Defined by the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0.

  • Leukemia-free survival [ Time Frame: Up to 2 years ]
    Will be evaluated.

  • Overall survival [ Time Frame: Up to 2 years ]
    Will be assessed by contacting the referring doctor of medicine (MD) or the patient every six months for two years following infusion of expanded cells.

  • Patient and infused expanded cord blood cells immune interaction [ Time Frame: Up to 2 years ]
    Will be assessed by performing host-donor studies.

  • Rate of complete remission (CR) [ Time Frame: Up to 2 years ]
    Will be evaluated.

  • Rate of complete remission with incomplete blood count recovery (CRi) [ Time Frame: Up to 2 years ]
    Will be evaluated.

  • Rate of complete remission with partial recovery of platelet count (CRp) [ Time Frame: Up to 2 years ]
    Will be evaluated.

  • Time to neutrophil recovery [ Time Frame: Up to 2 years ]
    Defined as absolute neutrophil count (ANC) > 100/ul and 500/ul.


Estimated Enrollment: 15
Actual Study Start Date: December 10, 2012
Estimated Study Completion Date: August 5, 2018
Estimated Primary Completion Date: August 5, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (ex vivo expanded cord blood progenitors)
Patients receive filgrastim SC or IV on days 1-7, fludarabine phosphate IV QD over 30 minutes on days 2-6, cytarabine IV QD over 4 hours on days 2-6, and ex vivo-expanded cord blood progenitor cells IV over 30 minutes on day 8.
Drug: Cytarabine
Given IV
Other Names:
  • .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
  • Cytosar-U
  • Cytosine Arabinoside
  • Cytosine-.beta.-arabinoside
  • Cytosine-beta-arabinoside
  • Erpalfa
  • Starasid
  • Tarabine PFS
  • U 19920
  • U-19920
  • Udicil
  • WR-28453
Procedure: Ex Vivo-Expanded Cord Blood Progenitor Cell Infusion
Given IV
Biological: Filgrastim
Given SC or IV
Other Names:
  • Filgrastim XM02
  • Filgrastim-sndz
  • G-CSF
  • Granix
  • Neupogen
  • r-metHuG-CSF
  • Recombinant Methionyl Human Granulocyte Colony Stimulating Factor
  • rG-CSF
  • Tbo-filgrastim
  • Tevagrastim
  • Zarxio
Drug: Fludarabine Phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-
  • Beneflur
  • Fludara
  • SH T 586

Detailed Description:

PRIMARY OBJECTIVES:

I. Assess the safety of infusing "off-the-shelf" non-human leukocyte antigen (HLA) matched expanded cord blood cells as supportive care following administration of fludarabine phosphate, cytarabine, and filgrastim (FLAG) consolidation or reinduction chemotherapy in pediatric and young adult patients with acute myeloid leukemia (AML) or acute leukemia of ambiguous lineage.

SECONDARY OBJECTIVES:

I. Assess the kinetics of autologous recovery when compared to historical cohorts.

II. Assess the ability of the product to provide transient myeloid engraftment/recovery.

III. Examine the in vivo persistence of the ex vivo expanded cord blood cells by determining the kinetics and durability of potential engraftment.

IV. Develop understanding of the underlying immune interaction between the patient (host) and the infused expanded cord blood cells (donor) by performing in vitro analyses to assess host-mediated rejection of the non HLA-matched expanded cells.

V. Estimate the incidence of clinically significant infections (e.g. bacterial, viral, or fungal) observed in patients treated with FLAG consolidation or reinduction chemotherapy followed by "off-the-shelf" non-HLA matched expanded cord blood cells.

VI. Assess the percentage of patients that achieve complete remission (CR)/complete remission with incomplete blood count recovery (CRi)/complete remission with partial recovery of platelet count (CRp) with this therapy approach.

VII. Assess long term efficacy (overall survival [OS]/disease free survival [DFS]) of FLAG consolidation or reinduction chemotherapy followed by "off-the-shelf" non HLA matched expanded cord blood cells in pediatric AML or acute leukemia of ambiguous lineage patients during long term follow up.

OUTLINE:

Patients receive filgrastim subcutaneously (SC) or intravenously (IV) on days 1-7, fludarabine phosphate IV over 30 minutes once daily (QD) on days 2-6, cytarabine IV QD over 4 hours on days 2-6, and ex vivo-expanded cord blood progenitor cells IV over 30 minutes on day 8.

After completion of study treatment, patients are followed up every 6 months for 2 years.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   6 Months to 30 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have a diagnosis of AML or acute leukemia of ambiguous lineage according to World Health Organization (WHO) classification with >= 5% of disease in bone marrow (BM); patients with blast count < 5% are eligible if immunophenotype, molecular or cytogenetic signature are consistent with AML as determined by primary treating oncologist; patients with extramedullary disease, or biopsy-proven isolated myeloid sarcoma (myeloblastoma, chloroma, including leukemia cutis) are eligible regardless of marrow involvement
  • AML or acute leukemia of ambiguous lineage:

    • If relapse AML or acute leukemia of ambiguous lineage:

      • Must have a prior diagnosis of AML or acute leukemia of ambiguous lineage and be in 1st or greater relapse as evidenced by morphology, immunophenotype, molecular or cytogenetic signature
      • Must not have received prior reinduction therapy for this relapse
    • If primary refractory AML or acute leukemia of ambiguous lineage:

      • Must have had a prior diagnosis of AML or acute leukemia of ambiguous lineage and
      • Must not have received more than 3 previous induction attempts
    • If primary AML or acute leukemia of ambiguous lineage newly diagnosed or in remission

      • Primary treating oncologist must have deemed patient unable to complete standard treatment therapy and selected FLAG as appropriate alternative regimen
    • If prior diagnosis of acute lymphoblastic leukemia must have evidence of transformation to AML or acute leukemia of ambiguous lineage as evidenced by morphology, immunophenotype, molecular or cytogenetic signature
    • Patients meeting above criteria are eligible regardless of central nervous system (CNS) classification
  • Recipients of prior allogeneic hematopoietic stem cell transplantation for AML or acute leukemia of ambiguous lineage are eligible if they do not have graft-versus-host disease (GVHD) or they have quiescent GVHD whether or not they are receiving immunosuppressive therapy
  • Must have a Lansky or Karnofsky performance status of >= 50; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
  • Patients must have recovered from the acute toxicity of all prior chemotherapy; patients may not have received cytotoxic chemotherapy within 2 weeks of first dose of G-CSF (filgrastim) therapy, with exception of hydroxyurea, which is allowed for up to 24 hours prior to first dose of G-CSF, and intrathecal chemotherapy, which is allowed prior to, or in the 1st 72 hours after start of G-CSF therapy
  • The following amounts of time must have elapsed prior to entry on study:

    • 2 weeks from local radiation therapy (XRT)
    • 8 weeks from prior craniospinal or if > 50% of the pelvis has been irradiated
    • 6 weeks must have elapsed if other bone marrow radiation has occurred
  • Creatinine within normal range for age (per institutional defined lab value ranges)
  • Direct bilirubin =< 1.5 upper limit of normal (ULN) age unless elevation thought to be due or hepatic infiltration by the hematologic malignancy
  • Alanine aminotransferase (ALT) < 5 x ULN age
  • Adequate cardiac function as defined as shortening fraction of > 27% OR ejection fraction of > 50%
  • Patients must have a corrected QT (QTc) interval < 450 ms on baseline electrocardiogram (EKG)
  • Patients must demonstrate a respiratory rate that is within normal limits for age, measured when afebrile and at rest (measured for a full minute) and pulse oximetry >= 93% on room air
  • Signed informed consent
  • Patient must have a life expectancy of at least 2 months
  • Females of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment
  • Females of childbearing potential and males should agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation

Exclusion Criteria:

  • Recipients of prior allogeneic hematopoietic stem cell transplant (HSCT) with active acute or chronic GVHD
  • Patients with history of Down's syndrome, Fanconi anemia or other known marrow failure condition
  • Patients currently receiving other investigational drugs are not eligible
  • Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol with the exception of intrathecal chemotherapy; this includes the tyrosine kinase inhibitor sorafenib which must not be initiated until patient demonstrates count recovery
  • Patients with a systemic fungal, bacterial, viral, or other infection not controlled despite appropriate antibiotics or other treatment; uncontrolled systemic infections require infectious disease consultation for verification
  • Patients who are platelet refractory prior to initiation of protocol therapy; platelet refractoriness is defined by platelet count < 50 K when platelet count is obtained 1 hour post platelet transfusion
  • Pregnant or lactating patients
  • Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01701323


Locations
United States, Georgia
Emory University/Winship Cancer Institute
Atlanta, Georgia, United States, 30322
United States, Washington
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Seattle Children's Research Institute Center for Clinical and Translational Research
Investigators
Principal Investigator: Ann Dahlberg Fred Hutch/University of Washington Cancer Consortium
  More Information

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT01701323     History of Changes
Other Study ID Numbers: 2584.00
NCI-2012-01724 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2584
2378
2584.00 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
P30CA015704 ( U.S. NIH Grant/Contract )
First Submitted: October 3, 2012
First Posted: October 5, 2012
Last Update Posted: July 2, 2017
Last Verified: June 2017

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Acute Disease
Neoplasms by Histologic Type
Neoplasms
Disease Attributes
Pathologic Processes
Fludarabine
Fludarabine phosphate
Cytarabine
Vidarabine
Lenograstim
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antiviral Agents
Anti-Infective Agents
Adjuvants, Immunologic