Laboratory-Treated Donor Cord Blood Cell Infusion Following Combination Chemotherapy in Treating Younger Patients With Relapsed or Refractory Acute Myeloid Leukemia
|Acute Leukemia of Ambiguous Lineage Adult Acute Myeloid Leukemia in Remission Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11 Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11 Adult Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1 Adult Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A Adult Acute Promyelocytic Leukemia With PML-RARA Alkylating Agent-Related Acute Myeloid Leukemia 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 Design:||Intervention Model: Single Group Assignment
Masking: No masking
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|
- Delayed marrow recovery [ Time Frame: After day 42 ]
- 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 ]
- Occurrence of grade > 3 infusional toxicity with administration of ex vivo expanded cord blood therapy according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 2 years ]
- Occurrence of transfusion associated GVHD [ Time Frame: Up to 2 years ]
- Rates of treatment related mortality [ Time Frame: Up to 2 years ]
- In vivo persistence of ex vivo expanded cellular therapy 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 [ Time Frame: Up to 2 years ]
- Incidence of grade 3 or 4 infections per NCI CTCAE version 4 in the neutropenic period following FLAG administration [ Time Frame: Up to 2 years ]
- Incidence of grade > 3 chemotherapy-related toxicity in the first 30 days following FLAG therapy defined by NCI CTCAE version 4.0 [ Time Frame: Up to 30 days ]
- Leukemia-free survival [ Time Frame: Up to 2 years ]
- Overall survival [ Time Frame: Up to 2 years ]
- Patient and infused expanded cord blood cells immune interaction by performing host-donor studies [ Time Frame: Up to 2 years ]
- Rate of CR [ Time Frame: Up to 2 years ]
- Rate of CRi [ Time Frame: Up to 2 years ]
- Rate of CRp [ Time Frame: Up to 2 years ]
- Time to neutrophil recovery (absolute neutrophil count [ANC] > 100/ul and 500/ul) [ Time Frame: Up to 2 years ]
|Study Start Date:||December 2012|
|Estimated Study Completion Date:||August 2018|
|Estimated Primary Completion Date:||August 2018 (Final data collection date for primary outcome measure)|
Experimental: Treatment (ex vivo expanded cord blood progenitors)
Patients receive filgrastim SC or IV on days 1-7, fludarabine phosphate IV over 30 minutes on days 2-6, cytarabine IV over 4 hours on days 2-6, and ex vivo-expanded cord blood progenitor cells IV over 30 minutes on day 8.
Other Names:Procedure: Ex Vivo-Expanded Cord Blood Progenitor Cell Infusion
Given IVBiological: Filgrastim
Given SC or IV
Other Names:Drug: Fludarabine Phosphate
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 FLAG (fludarabine phosphate, cytarabine, and filgrastim) consolidation or reinduction chemotherapy in pediatric and young adult patients with acute myeloid leukemia (AML) or acute leukemia of ambiguous lineage.
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.
Patients receive filgrastim subcutaneously (SC) or intravenously (IV) on days 1-7, fludarabine phosphate IV over 30 minutes on days 2-6, cytarabine IV 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01701323
|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|
|Principal Investigator:||Ann Dahlberg||Fred Hutch/University of Washington Cancer Consortium|