Clinical Trials /

Safety Study of CPX-351 in Children With Relapsed Leukemia or Lymphoma

NCT01943682

Description:

The purpose of this study is to test the safety of a study drug called CPX-351. This drug has been tested in adults but not yet in children and adolescents. This study tests different doses of the drug to see which dose is safer in children and adolescents. Patients who have blood cancer are being asked to take part in this study . Blood cancers may include leukemia and lymphoma. Patients able to be in this study have already been treated with standard chemotherapy for their disease and the disease is still growing or has come back. CPX-351 is a drug that is not yet approved by the United States Food and Drug Administration (FDA) and is only used in research studies like this one. CPX-351 is made up of two chemotherapy drugs that patients may have already received called cytarabine and daunorubicin that are now packaged together. Another purpose of this study is to collect blood samples for special research studies. Researchers want to study how much of the CPX-351 is in the body over time. These studies are call pharmacokinetic studies or PK studies for short. PK studies require the collection of several blood samples before and after participants are given the study drug.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Safety Study of CPX-351 in Children With Relapsed Leukemia or Lymphoma
  • Official Title: A Phase I/Pilot Study of CPX-351 for Children, Adolescents and Young Adults With Recurrent or Refractory Hematologic Malignancies

Clinical Trial IDs

  • ORG STUDY ID: CPX-MA-1201
  • SECONDARY ID: 2013-4305
  • NCT ID: NCT01943682

Conditions

  • Acute Myeloid Leukemia
  • Acute Lymphoblastic Leukemia
  • Burkitt Lymphoma
  • Diffuse Large Cell Lymphoma
  • Gray Zone Lymphoma
  • Lymphoblastic Lymphoma
  • Anaplastic Large Cell Lymphoma
  • Hodgkin Lymphoma

Interventions

DrugSynonymsArms
CPX-351CPX-351

Purpose

The purpose of this study is to test the safety of a study drug called CPX-351. This drug has been tested in adults but not yet in children and adolescents. This study tests different doses of the drug to see which dose is safer in children and adolescents. Patients who have blood cancer are being asked to take part in this study . Blood cancers may include leukemia and lymphoma. Patients able to be in this study have already been treated with standard chemotherapy for their disease and the disease is still growing or has come back. CPX-351 is a drug that is not yet approved by the United States Food and Drug Administration (FDA) and is only used in research studies like this one. CPX-351 is made up of two chemotherapy drugs that patients may have already received called cytarabine and daunorubicin that are now packaged together. Another purpose of this study is to collect blood samples for special research studies. Researchers want to study how much of the CPX-351 is in the body over time. These studies are call pharmacokinetic studies or PK studies for short. PK studies require the collection of several blood samples before and after participants are given the study drug.

Detailed Description

      Cytarabine in combination with an anthracycline is a frequently used chemotherapy platform
      for both newly diagnosed and relapsed/refractory acute myeloid leukemia (AML) and other
      hematologic malignancies. Synergistic antitumor activity has been demonstrated between
      cytarabine and daunorubicin that is dependent upon the ratio of the drugs with the best
      therapeutic effect observed with a cytarabine to daunorubicin ratio of 5:1 in in vitro and in
      vivo models. CPX-351 is a liposomal preparation of cytarabine and daunorubicin that maintains
      this therapeutic drug ratio 24 hours post infusion. The altered biodistribution from
      encapsulation may result in a greater therapeutic effect in patients with relapsed
      hematologic malignancies and demonstrate greater tolerability than non-liposomal cytarabine
      and daunorubicin.

      This is a single institution phase-I pilot study that aims to assess the pharmacokinetics,
      toxicity and tolerability of CPX-351 in pediatric and young adults with relapsed/refractory
      hematologic malignancies. Subjects will receive a single course of CPX-351 administered on
      Days 1, 3, and 5. The study will first open to children in a dose exploration phase, and then
      be available to an expanded cohort, which will be open to children and young adults once a
      tolerable dose has been determined.
    

Trial Arms

NameTypeDescriptionInterventions
CPX-351ExperimentalCPX-351 is made up of two chemotherapy drugs that patients may have already received called cytarabine and daunorubicin that are now packaged together. Subjects will receive a single course of CPX-351 administered on Days 1, 3, and 5.
  • CPX-351

Eligibility Criteria

        Inclusion Criteria:

          -  Age

               1. 12 months to 21 years at time of enrollment into dose exploration phase

               2. 12 months to 30 years at time of enrollment into expanded phase

          -  Diagnosis: Patients must have a diagnosis of a hematologic malignancy (acute myeloid
             leukemia (AML), acute lymphoblastic leukemia (ALL), or aggressive lymphoma.

          -  Disease Status

               1. Acute myeloid leukemia - patients with non-therapy related AML must be in first
                  or greater relapse or have refractory disease to at least two courses of
                  induction therapy.

               2. Acute lymphoid leukemia - patients with ALL must be in second or greater relapse
                  or have relapsed disease refractory to re-induction therapy.

               3. Aggressive Lymphoma - patients must have relapsed or refractory disease for which
                  there is no known curative therapy available. Patients must have measurable
                  disease by CT scan.

          -  Performance status: Karnofsky > or = to 50% or Lansky > or = to 50.

          -  Prior therapy: Patients must have fully recovered from acute toxicities of prior
             therapy.

               1. Hematopoetic Stem cell transplant (HSCT): Patients who relapsed after HSCT, are
                  eligible provided they have no evidence of active graft versus host disease
                  (GVHD) and are at least 2 months post-transplant.

               2. Anthracycline exposure: Patients who have not previously had TBI (total body
                  irradiation) must have a total previous cumulative anthracycline exposure ≤ 450
                  mg/m2 daunorubicin equivalents. Patients who have had prior TBI or radiation to
                  the mediastinum must have a previous cumulative anthracycline exposure e ≤ 300
                  mg/m2 daunorubicin equivalents.

               3. Cytotoxic therapy:

                    1. AML and Lymphoma: at least 14 days must have elapsed since the completion of
                       systemic cytotoxic therapy, with the exception of hydroxyurea.

                    2. ALL: patients who relapsed while receiving standard maintenance therapy do
                       not have a waiting period. At least 14 days must have elapsed since
                       receiving systemic cytarabine or an anthracycline/anthracenedione.

                    3. Intrathecal cytotoxic therapy: no waiting period is required for patients
                       receiving intrathecal cytarabine, methotrexate and/or hydrocortisone. At
                       least 14 days must have elapsed since receiving liposomal cytarabine in
                       intrathecal injection.

          -  Organ function requirements

               1. Adequate bone marrow function - platelet count >/= 20,000/uL (may receive
                  platelet transfusions; Hemoglobin >/= 8 g/dL (may receive red blood cell
                  transfusions)

               2. Adequate Renal function - a maximum serum creatinine is based on age/gender.
                  Subjects that do not meet eligibility criteria based upon serum creatinine may
                  meet eligibility criteria based upon a 24 hour creatinine clearance or
                  radioisotope determined GFR >/= 70 mL/min/1.73 m2.

               3. Adequate liver function - Direct bilirubin </= 1.5 x upper limit of normal (ULN)
                  for age and SGPT (ALT) < 5.0 x upper limit of normal (ULN) for age and
                  institution (unless elevation is related to leukemia involvement).

               4. Adequate cardiac function - Shortening fraction of >/= 27% by echocardiogram, or
                  Ejection fraction of >/= 50% by gated radionuclide study or echocardiogram.

               5. Central Nervous system function - patients with seizure disorder may be enrolled
                  if on anticonvulsants and well controlled and CNS toxicity </= Grade 2.

        Exclusion Criteria:

          -  Patients with the following diagnosis are not eligible: acute promyelocytic leukemia
             (APML), Down Syndrome, Fanconi Anemia, acute lymphoblastic leukemia with central
             nervous system leukemia (CNS status 3), Wilson's disease

          -  Pregnant or breast-feeding women. Males and females of reproductive potential may not
             participate unless they have agreed to use an effective method of contraception.

          -  Concomitant medications

               1. Growth factors- growth factors that support platelet or white cell number or
                  function must not be administered within 7 days prior to enrollment.

               2. Investigational drugs - patients currently receiving another investigational drug
                  are not eligible.

               3. Anti-cancer agents- patients who are currently receiving other anti-cancer agents
                  are not eligible with the exception of intrathecal cytarabine and oral
                  hydroxyurea. Hydroxyurea must be discontinued 24 hours prior to initiation of
                  protocol therapy.

          -  Infection: Patients who have an uncontrolled infection are not eligible.

          -  Patients who in the opinion of the investigator may not be able to comply with the
             safety monitoring requirements of the study are not eligible.

          -  History of Wilson's disease or other copper-metabolism disorder

          -  Major surgery within 4 weeks of enrollment.

          -  Greater than 13.6 Gy prior radiation to the mediastinum
      
Maximum Eligible Age:30 Years
Minimum Eligible Age:12 Months
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Determine rate of dose limiting toxicities
Time Frame:56 days
Safety Issue:
Description:Any Grade 3 or greater adverse event that can be possible/probably/or definitely attributable to CPX-351 that occurs between Day 1 and Day 56.

Secondary Outcome Measures

Measure:Tumor measurement by bone marrow biopsy, blood counts, and/or PET/CT scan
Time Frame:28 days
Safety Issue:
Description:Tumor measurements will be used to assess disease response per standard response criteria for acute myeloid leukemia, acute lymphoid leukemia and lymphoma.
Measure:Serum levels of biomarkers (troponin-1, troponin-T, and B-type natriuretic) of cardiac injury.
Time Frame:30 days
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Children's Hospital Medical Center, Cincinnati

Trial Keywords

  • Relapsed acute myeloid leukemia
  • non-therapy related acute myeloid leukemia
  • Refractory acute myeloid leukemia
  • Untreated acute myeloid leukemia
  • Lymphoma
  • Leukemia

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