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Pilot Study Evaluating the Use of Ex Vivo Expanded Cord Blood Progenitors as Supportive Care Following Induction Chemotherapy (FLAG) in Patients With Relapsed/Refractory AML


N/A
2 Years
30 Years
Open (Enrolling)
Both
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(15;17)(q22;q12), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), Recurrent Adult Acute Myeloid Leukemia, Recurrent Childhood Acute Myeloid Leukemia

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Trial Information

Pilot Study Evaluating the Use of Ex Vivo Expanded Cord Blood Progenitors as Supportive Care Following Induction Chemotherapy (FLAG) in Patients With Relapsed/Refractory AML


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) reinduction chemotherapy in pediatric and young adult
patients with relapsed/refractory acute myeloid leukemia (AML).

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

V. 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.

VI. Assess long term efficacy (overall survival [OS]/disease free survival [DFS]) of FLAG
reinduction chemotherapy followed by "off-the-shelf" non HLA matched expanded cord blood
cells in pediatric relapsed AML 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 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.


Inclusion Criteria:



- Patients must have a diagnosis of AML according to World Health Organization (WHO)
classification with >= 5% of disease in bone marrow (BM), with or without
extramedullary disease or biopsy-proven isolated myeloid sarcoma (myeloblastoma,
chloroma, including leukemia cutis) in the absence of marrow involvement

- AML:

- If relapse AML:

- Must have a prior diagnosis of AML and be in 1st or greater relapse

- Must not have received prior reinduction therapy for this relapse

- If primary refractory AML:

- Must have had a prior diagnosis of AML and

- Must not have received more than 3 previous induction attempts

- Patients must be classified as central nervous system (CNS)1 or CNS 2 and
without clinical signs of CNS leukemia such as cranial nerve palsy; patients
with CNS 3 disease are not eligible

- 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 calculated QT (QTc) interval < 450 ms on baseline echocardiogram

- 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:

- Recipient of prior allogeneic hematopoietic stem cell transplant (HCT)

- Patients with history of Down's syndrome, Fanconi anemia or other known marrow
failure condition

- Patients with central nervous system (CNS) 3 disease or symptomatic CNS2 disease are
not eligible

- 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 < 50K 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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Time Frame:

Up to 2 years

Safety Issue:

Yes

Principal Investigator

Colleen Delaney

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Authority:

United States: Food and Drug Administration

Study ID:

2584.00

NCT ID:

NCT01701323

Start Date:

December 2012

Completion Date:

Related Keywords:

  • Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
  • Adult Acute Myeloid Leukemia With Del(5q)
  • Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
  • Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
  • Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
  • Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
  • Recurrent Adult Acute Myeloid Leukemia
  • Recurrent Childhood Acute Myeloid Leukemia
  • Congenital Abnormalities
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid

Name

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer ConsortiumSeattle, Washington  98109
Emory UniversityAtlanta, Georgia  30322