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

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

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 Lin

Brief Summary: 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.

Detailed Summary:

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 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.

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 e
Sponsor: Fred Hutchinson Cancer Research Center

Current Primary Outcome:

  • 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 ]


Original Primary Outcome:

  • 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 graft-versus-host disease (GVHD) [ Time Frame: Up to 2 years ]
  • 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 ]
  • Delayed marrow recovery [ Time Frame: After day 42 ]
  • Rates of treatment related mortality [ Time Frame: Up to 2 years ]


Current Secondary Outcome:

  • 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 ]


Original Secondary Outcome:

  • Time to neutrophil recovery (absolute neutrophil count [ANC] > 100/ul and 500/ul) [ 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 (CD)33/14 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 ]
  • 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 ]
  • Overall survival [ Time Frame: Up to 2 years ]
  • Leukemia-free survival [ Time Frame: Up to 2 years ]


Information By: Fred Hutchinson Cancer Research Center

Dates:
Date Received: October 3, 2012
Date Started: December 2012
Date Completion: August 2018
Last Updated: March 14, 2017
Last Verified: March 2017