Brief Title
Clofarabine, Cytarabine, and Filgrastim Followed by Infusion of Non-HLA Matched Ex Vivo Expanded Cord Blood Progenitors in Treating Patients With Acute Myeloid Leukemia
Official Title
Clofarabine in Combination With Cytarabine (Ara-C) and G-CSF Priming Followed by Infusion of Ex Vivo Expanded Cord Blood Progenitors for Patients With AML
Brief Summary
This phase I trial is studying the safety and potential efficacy of infusing non-human
leukocyte antigen (HLA) matched ex vivo expanded cord blood progenitors following treatment
with clofarabine and cytarabine for patients with acute myeloid leukemia (AML). The
combination of clofarabine, cytarabine (Ara-C) and granulocyte colony-stimulating factor
(G-CSF) has been tested in earlier studies for the treatment of acute myeloid leukemia. In
these previous clinical trials, this combination of drugs has been shown to have an
anti-leukemia effect. However, the combination of clofarabine and Ara-C is profoundly
myelosuppressive and immunosuppressive causing periods of neutropenia potentially lasting
more than three weeks. During this period, patients are at increased risk of infections that
can result in an increased risk of death. G-CSF is a growth factor that is used to help the
white blood cells recover more quickly, but even with G-CSF, the use of clofarabine and Ara-C
is often limited by the need to take long breaks between treatments to allow blood counts to
recover. In our lab we have developed a method of growing or "expanding" blood stem cells
(cells that give rise to the blood system) from umbilical cord blood. We are doing this study
to find out if giving these expanded cells after chemotherapy is safe, helps the blood system
recover more quickly from chemotherapy to allow shorter breaks between treatments, and
decreases the risk of infection
Detailed Description
PRIMARY OBJECTIVES:
I. Assess the safety of infusing off-the-shelf non-HLA matched expanded cord blood cells
following administration of cytarabine hydrochloride (GCLAC) for patients with AML.
SECONDARY OBJECTIVES:
I. Assess the ability of the product to provide temporary myeloid engraftment.
II. Assess the kinetics/persistence of potential engraftment.
III. Assess the kinetics of autologous recovery when compared to historical cohorts.
IV. Assess the development of alloimmunization.
OUTLINE:
INDUCTION THERAPY: Patients receive clofarabine intravenously (IV) over 1 hour and cytarabine
hydrochloride IV over 2 hours on days 1-5. Patients receive an infusion of non-HLA matched ex
vivo expanded cord blood progenitors on day 6. Filgrastim (G-CSF) is administered
subcutaneously (SC) on days 0-5 and from day 7 until blood counts recover. Treatment
modifications may apply according to response.
CONSOLIDATION THERAPY: Patients receive clofarabine IV over 1 hour and cytarabine
hydrochloride IV over 2 hours on days 1-5. Patients also receive G-CSF SC beginning on day 0
and continuing until blood counts recover.
Patients may receive treatment for 1-4 courses in the absence of disease progression or
unacceptable toxicity.
After completion of study treatment, patients are followed up every 3-6 months for 2 years
and then annually for 3 years.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Grade 3 or greater infusion toxicity, as defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
Condition
Adult Acute Megakaryoblastic Leukemia (M7)
Intervention
cytarabine
Study Arms / Comparison Groups
Treatment (chemotherapy, G-CSF, cord blood infusion)
Description: INDUCTION THERAPY: Patients receive clofarabine IV over 1 hour and cytarabine hydrochloride IV over 2 hours on days 1-5. Patients receive an infusion of non-HLA matched ex vivo expanded cord blood progenitors on day 6. G-CSF is administered SC on days 0-5 and from day 7 until blood counts recover. Treatment modifications may apply according to response. CONSOLIDATION THERAPY: Patients receive clofarabine IV over 1 hour and cytarabine hydrochloride IV over 2 hours on days 1-5. Patients also receive G-CSF SC beginning on day 0 and continuing until blood counts recover.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
29
Start Date
December 2009
Completion Date
October 24, 2012
Primary Completion Date
September 2012
Eligibility Criteria
Inclusion Criteria:
- Cohort A: Diagnosis of AML by World Health Organization (WHO) criteria, either
relapsed or refractory; acute promyelocytic leukemia [Acute promyelocytic leukemia
with t(15;17)(q22;q12) and variants] will be eligible only after failure of a regimen
containing arsenic trioxide; patients in this cohort must have had an initial
remission duration of < 1 year and cannot have received any prior salvage chemotherapy
- Cohort B: Untreated AML patients, excluding those with favorable cytogenetic or
molecular abnormalities per the European LeukemiaNet recommendations
- Cohort C: Untreated AML patients, including those with favorable cytogenetic or
molecular abnormalities per the European LeukemiaNet recommendations
- The first three patients enrolled in cohorts A and B must be less than 60 years old;
thereafter, patients aged >= 18 and =< 70 are eligible
- The first three patients enrolled in cohorts A and B must have an Eastern Cooperative
Oncology Group (ECOG) performance status of 0 -1; thereafter, ECOG performance status
of 0-2 is required
- Serum creatinine =< 1.0 mg/dL; if serum creatinine > 1.0 mg/dl, then the estimated
glomerular filtration rate (GFR) must be > 60 mL/min/1.73 m^2 as calculated by the
Modification of Diet in Renal Disease equation where predicted GFR (ml/min/1.73 m^2) =
186 X (Serum Creatinine)^-1.154 X (age in years)^-0.203 X (0.742 if patient is female)
X (1.212 if patient is black)
- Serum total bilirubin =< 1.5 x upper limit of normal (ULN) unless elevation is thought
to be due to Gilbert's syndrome, hemolysis, or hepatic infiltration by the hematologic
malignancy
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 X ULN, unless
elevation is thought to be due to hepatic infiltration by the hematologic malignancy
- Alkaline phosphatase =< 2.5 x ULN
- Capable of understanding the investigational nature, potential risks and benefits of
the study, and able to provide valid informed consent
- Female patients of childbearing potential must have a negative serum pregnancy test
within 2 weeks prior to enrollment
- Male and female patients must be willing to use an effective contraceptive method
during the study and for a minimum of 90 days after study treatment
Exclusion Criteria:
- Allogeneic transplant recipients
- Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as
specified in the protocol with the exception of intrathecal chemotherapy administered
on days that are not concurrent with clofarabine and cytarabine
- Have any other severe concurrent disease, or have a history of serious organ
dysfunction or disease involving the heart, kidney, liver (including symptomatic
hepatitis, veno-occlusive disease), or other organ system dysfunction
- Patients with a systemic fungal, bacterial, viral, or other infection not controlled
(defined as exhibiting ongoing signs/symptoms related to the infection and without
improvement, despite appropriate antibiotics or other treatment)
- 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
Gender
All
Ages
18 Years - 70 Years
Accepts Healthy Volunteers
No
Contacts
Colleen Delaney, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT01031368
Organization ID
2335.00
Secondary IDs
NCI-2009-01333
Responsible Party
Sponsor
Study Sponsor
Nohla Therapeutics, Inc.
Collaborators
National Cancer Institute (NCI)
Study Sponsor
Colleen Delaney, Principal Investigator, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Verification Date
February 2019