Expanded Cord Blood Cell Infusion Following Combination Chemotherapy in Younger Patients With Relapsed or Refractory Acute Myeloid Leukemia

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

This pilot clinical trial studies infusion of expanded cord blood hematopoietic progenitor cells following combination chemotherapy in treating younger patients with acute myeloid leukemia that has relapsed or has not responded 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 expanded cord blood hematopoietic progenitor cells may be able to replace blood-forming cells that were destroyed by chemotherapy. This cellular therapy may decrease the risk of infection following chemotherapy.

Study Overview

• Status: Terminated
• Conditions: Acute Myeloid Leukemia; Acute Leukemia of Ambiguous Lineage
• Intervention / Treatment: Drug: Cytarabine; Drug: Fludarabine Phosphate; Biological: Ex-Vivo Expanded Cord Blood Progenitor Cell Infusion; Drug: Filgrastim

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University/Winship Cancer Institute
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 30 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)
• 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

• 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
• Adequate cardiac, renal, pulmonary, and hepatic function
• 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
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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; Drug: Fludarabine Phosphate; Given IV; Biological: Ex-Vivo Expanded Cord Blood Progenitor Cell Infusion; Given IV; Other Names: NLA101; Dilanubicel; Drug: Filgrastim; Given SC or IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of NCI CTCAE grade > 3 infusional toxicities		Up to 2 years
Occurrence of transfusion associated graft versus host disease		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		Up to 2 years
Incidence of delayed marrow recovery	Failure to achieve ANC >= 500 cells/µl by day 42 post treatment with marrow cellularity < 5% and marrow blast count < 5%.	Up to day 42
Rate of treatment related mortality		Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival		Up to 2 years
Time to neutrophil recovery	ANC >= 100 cells/ul and 500 cells/ul	Up to 2 years
In vivo persistence of ex vivo expanded cellular therapy	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.	Up to 2 years
Patient and infused expanded cord blood cells immune interaction	Assessed by performing host-donor studies.	Up to 2 years
Incidence of NCI CTCAE grade 3 or 4 infections		First 30 days following FLAG administration
Incidence of NCI CTCAE grade > 3 chemotherapy-related toxicity in the first 30 days following fludarabine phosphate, cytarabine, and filgrastim (FLAG) therapy		First 30 days following FLAG administration
Rate of complete remission		Up to 2 years
Leukemia-free survival		Up to 2 years

Collaborators and Investigators

• Sponsor: Nohla Therapeutics, Inc.
• Collaborators: National Cancer Institute (NCI); Fred Hutchinson Cancer Center
• Investigators: Principal Investigator: Ann Dahlberg, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2012
• Primary Completion (Actual): May 10, 2018
• Study Completion (Actual): May 10, 2018

Study Registration Dates

• First Submitted: October 3, 2012
• First Submitted That Met QC Criteria: October 3, 2012
• First Posted (Estimate): October 5, 2012

Study Record Updates

• Last Update Posted (Actual): March 1, 2019
• Last Update Submitted That Met QC Criteria: February 27, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Fludarabine; Fludarabine phosphate; Cytarabine
• Other Study ID Numbers: 2584; P30CA015704 (U.S. NIH Grant/Contract); NCI-2012-01724 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 2584.00 (Other Identifier: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No