Clofarabine, Cytarabine, and Filgrastim Followed by Infusion of Non-HLA Matched Ex Vivo Expanded Cord Blood Progenitors in Treating Patients With Acute Myeloid Leukemia

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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