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

Acute Myeloid Leukemia Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01701323
• Other study ID #: 2584
• Secondary ID: NCI-2012-0172425
• Status: Terminated
• Phase: Phase 1
• Start date: December 10, 2012
• Est. completion date: May 10, 2018

Study information

• Verified date: February 2019
• Source: Nohla Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: May 10, 2018
• Est. primary completion date: May 10, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 30 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Leukemia of Ambiguous Lineage
• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Biological:
• Ex-Vivo Expanded Cord Blood Progenitor Cell Infusion
Given IV

Drug:
• Cytarabine
Given IV
• Filgrastim
Given SC or IV
• Fludarabine Phosphate
Given IV

Locations

Country	Name	City	State
United States	Emory University/Winship Cancer Institute	Atlanta	Georgia
United States	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington

Sponsors (3)

Lead Sponsor	Collaborator
Nohla Therapeutics, Inc.	Fred Hutchinson Cancer Research Center, National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of NCI CTCAE grade > 3 infusional toxicities		Up to 2 years
Primary	Occurrence of transfusion associated graft versus host disease		Up to 2 years
Primary	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
Primary	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
Primary	Rate of treatment related mortality		Up to 2 years
Secondary	Time to neutrophil recovery	ANC >= 100 cells/ul and 500 cells/ul	Up to 2 years
Secondary	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
Secondary	Patient and infused expanded cord blood cells immune interaction	Assessed by performing host-donor studies.	Up to 2 years
Secondary	Incidence of NCI CTCAE grade 3 or 4 infections		First 30 days following FLAG administration
Secondary	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
Secondary	Rate of complete remission		Up to 2 years
Secondary	Leukemia-free survival		Up to 2 years
Secondary	Overall survival		Up to 2 years