Sorafenib in Combination With Cytarabine and Clofarabine in Patients With Refractory or Relapsed Hematologic Malignancies
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.
Acute Myeloid Leukemia
Infantile Leukemia (Both AML and ALL)
|Study Design:||Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: 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|
- 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 ] [ Designated as safety issue: Yes ]
|Study Start Date:||September 2009|
|Estimated Study Completion Date:||December 2014|
|Estimated Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Participants treated with sorafenib, cytarabine and clofarabine.
Please see detailed description.
Other Name: NexavarDrug: Cytarabine
Please see Detailed Description.
Other Name: Cytosine ArabinosideDrug: Clofarabine
Please see Detailed Description.
Other Name: Clolar
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).
|Contact: Hiroto Inaba, MD, PhDfirstname.lastname@example.org|
|United States, Tennessee|
|St. Jude Children's Research Hospital||Recruiting|
|Memphis, Tennessee, United States, 38105|
|Contact: Hiroto Inaba, MD, PhD 866-278-5833 email@example.com|
|Principal Investigator: Hiroto Inaba, MD, PhD|
|Principal Investigator:||Hiroto Inaba, MD, PhD||St. Jude Children's Research Hospital|