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Trial record 100 of 144 for:    "Acute promyelocytic leukemia"

Sorafenib in Combination With Cytarabine and Clofarabine in Patients With Refractory or Relapsed Hematologic Malignancies

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00908167
Recruitment Status : Completed
First Posted : May 25, 2009
Last Update Posted : January 12, 2018
National Cancer Institute (NCI)
Information provided by (Responsible Party):
St. Jude Children's Research Hospital

Brief Summary:
This is a Phase I study that determines a tolerable combination of sorafenib, when given sequentially with cytarabine and clofarabine and determines the feasibility of administering this drug combination in patients with relapsed or refractory hematologic malignancies including acute myeloid leukemia (AML), acute promyelocytic leukemia (APL), acute lymphoblastic leukemia (ALL), infantile leukemia (both either AML and/or ALL). AML with prior myelodysplastic syndrome (MDS), myelodysplastic/myeloproliferative neoplasms, and biphenotypic leukemia.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Infantile Leukemia (Both AML and ALL) Myelodysplastic Syndrome Myelodysplastic/Myeloproliferative Neoplasms Biphenotypic Leukemia Drug: Sorafenib Drug: Cytarabine Drug: Clofarabine Phase 1

Detailed Description:

Research is performed in patients with age of ≥ 0 months old and < 31 years old. In course 1, sorafenib will be given orally (PO) on days 1 to 7. Pharmacokinetic studies on days 1 and 7 and pharmacodynamic assessment on day 8 will be performed. Inter-patient dose escalation or de-escalation of clofarabine and sorafenib will be performed based on tolerability and toxicity. On days 8 to 12, clofarabine and cytarabine will be administered intravenously (IV) without concurrent twice daily sorafenib. Sorafenib will then be given on days 15 to 28 (14 days). Cytarabine and clofarabine may be given before day 8 when the treating physician feels it is necessary after consulting with the primary investigator based on the participant's clinical condition (e.g. disease progression). Intrathecal (IT) methotrexate (age-adjusted doses) with leucovorin rescue (24 and 30 hours after IT therapy) can be given on day 8. Participants with central nervous system (CNS) disease can receive IT therapy weekly until the cerebrospinal fluid (CSF) becomes free of leukemia (minimum of 4 doses). Triple intrathecal therapy with methotrexate, hydrocortisone and cytarabine is allowed other than day 8 therapy.

Response evaluation will be performed on day 22 (or 15 days after initiation of cytarabine and clofarabine) in the first course. One course of therapy will be for 28 days unless disease progression is seen. Participants may receive subsequent courses (up to 5 courses) if there is no disease progression or unacceptable toxicity. Sorafenib is given on days 1 to 7 and 15 to 28 in subsequent courses, and cytarabine with or without clofarabine will be administered starting on days 8 to 12 (clofarabine can be removed after course 2).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 44 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Pharmacokinetic, Pharmacodynamic and Feasibility Study of Sorafenib in Combination With Cytarabine and Clofarabine in Patients With Refractory or Relapsed Hematologic Malignancies
Study Start Date : September 2009
Actual Primary Completion Date : June 2015
Actual Study Completion Date : June 2015

Arm Intervention/treatment
Research Participants
Participants treated with sorafenib, cytarabine and clofarabine.
Drug: Sorafenib
Please see detailed description.
Other Name: Nexavar

Drug: Cytarabine
Please see Detailed Description.
Other Name: Cytosine Arabinoside

Drug: Clofarabine
Please see Detailed Description.
Other Name: Clolar

Primary Outcome Measures :
  1. To characterize a tolerable dose of sorafenib when given in combination with cytarabine and clofarabine in patients with relapsed/refractory hematologic malignancies. [ Time Frame: 4.5 years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 31 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients must have a diagnosis of acute myeloid leukemia (AML), acute promyelocytic leukemia (APL), acute lymphoblastic leukemia (ALL), infantile leukemia (either AML or ALL), AML with prior myelodysplastic syndrome (MDS), myelodysplastic/myeloproliferative neoplasms, or biphenotypic leukemia. Patients with treatment-related AML (t-AML) will be eligible, provided they meet all other eligibility criteria.
  • Current disease status must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life.

Patients must meet one of the following criteria:

  1. First or greater relapse,
  2. Refractory to 1 or more courses of induction or reinduction chemotherapy, or
  3. First or greater relapse after allogeneic hematopoietic stem cell transplantation (HSCT).

    • Age: participants must be < 31 years of age at the time of study entry.

St. Jude participants will include the following:

  • Participants currently on therapy at St. Jude, or within 3 years of completing therapy at St. Jude must be ≤ 24 years of age.
  • Other participants must be ≤ 21 years of age.

Performance status: Karnofsky >50% for ≥ 16 years of age; Lansky >50% for children <16 years of age.

Organ Function Requirements:

  1. Hepatic:

    • Serum direct bilirubin ≤2.0 mg/dl.
    • Alanine transaminase (ALT/SGPT) ≤4 x ULN
  2. Cardiovascular:

    • Shortening fraction of greater than or equal to 25% by echocardiogram

  3. Pulmonary:

    • Pulse oximetry ≥93% at room air

  4. Renal:

    • Creatinine clearance or radioisotope GFR greater than or equal to 70 mL/min/1.73m2 or serum creatinine based on age

  5. Pancreas:

    • Amylase and lipase ≤ 2 × upper limits of normal

Participant or legal guardian, in the opinion of the investigator, is capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent. A signed informed consent must be obtained prior to any study specific procedures.

Exclusion Criteria:

  • Participants who have relapsed while on sorafenib therapy.
  • Uncontrolled hypertension, defined below:
  • Patients < 18 years old:

    • Diastolic Blood Pressure Within The Upper Limit Of Normal Defined as: A diastolic blood pressure (DBP) > the 95th percentile for age and gender despite optimal medical management.
  • Patients ≥ 18 years old

    • Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg despite optimal medical management. .
  • Use of concomitant chemotherapy, investigational agents, radiation therapy, or immunotherapy other than as specified in the protocol.
  • Use of investigational agents within 30 days or any anticancer therapy within 2 weeks before study entry with the exception of hydroxyurea, low dose cytarabine and intrathecal chemotherapy.
  • Any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the participant at undue risk to undergo treatment.
  • Participant 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).
  • Any significant concurrent disease, illness, or psychiatric disorder that would compromise participant safety or compliance, interfere with consent, study participation, follow-up, or interpretation of study results.
  • Participants must not receive concomitant medications known to inhibit platelet function or known to selectively inhibit cyclooxygenase-2 (COX-2) activity (i.e., all antipyretic and anti-inflammatory medications except acetaminophen).
  • There is no available information, as yet, regarding human fetal or teratogenic toxicities. Pregnancy tests with a negative result must be obtained in girls who are postmenarchal within 10 days before start of treatment. Women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation. Men and women should use adequate birth control for at least three months after the last administration of study treatment.
  • Pregnant or lactating.
  • Known human immunodeficiency virus (HIV) infection.
  • Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months
  • Cardiac disease: Congestive heart failure > class II NYHA. Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
  • Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
  • Pulmonary hemorrhage/bleeding event > CTCAE Grade 2 within 4 weeks of first dose of study drug.
  • Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of study drug
  • Serious non-healing wound, ulcer, or bone fracture.
  • Evidence or history of bleeding diathesis or coagulopathy.
  • Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug.
  • Concomitant use of St. John's Wort or rifampin (rifampicin)
  • Known or suspected allergy to any agent given in the course of this trial.
  • Any malabsorption problem.
  • Have had a diagnosis of another malignancy, unless the participant has been disease-free for at least 3 years following the completion of curative intent therapy with the following exceptions:

    • Participants with treated non-melanoma skin cancer, in situ, carcinoma, or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed.
    • Patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen (PSA) values are also eligible for this study if hormonal therapy has been initiated or a radical prostatectomy has been performed.
  • Participants who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study.
  • Inability or unwillingness of research participant or legal guardian or representative to give written informed consent.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00908167

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United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
Sponsors and Collaborators
St. Jude Children's Research Hospital
National Cancer Institute (NCI)
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Principal Investigator: Hiroto Inaba, MD, PhD St. Jude Children's Research Hospital

Additional Information:
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Responsible Party: St. Jude Children's Research Hospital Identifier: NCT00908167     History of Changes
Other Study ID Numbers: RELHEM
R01CA138744 ( U.S. NIH Grant/Contract )
NCI-2011-01252 ( Registry Identifier: NCI Clinical Trial Registration Program )
First Posted: May 25, 2009    Key Record Dates
Last Update Posted: January 12, 2018
Last Verified: July 2015
Keywords provided by St. Jude Children's Research Hospital:
acute myeloid leukemia
acute promyelocytic leukemia
acute lymphoblastic leukemia
Additional relevant MeSH terms:
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Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Neoplasms by Histologic Type
Leukemia, Myeloid
Bone Marrow Diseases
Hematologic Diseases
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs