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

NCT00908167 | Completed Phase 1

• 3 other identifiers: RELHEMR01CA138744NCI-2011-01252
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Myeloid Leukemia; Infantile Leukemia (Both AML and ALL); Myelodysplastic Syndrome; Myelodysplastic/Myeloproliferative Neoplasms; Biphenotypic Leukemia

Keywords

sorafenib; cytarabine; clofarabine; acute myeloid leukemia; acute promyelocytic leukemia; acute lymphoblastic leukemia

Outcome Measures

Primary Outcomes (1)

• To characterize a tolerable dose of sorafenib when given in combination with cytarabine and clofarabine in patients with relapsed/refractory hematologic malignancies.

  4.5 years

Study Arms (1)

Research Participants

OTHER

Participants treated with sorafenib, cytarabine and clofarabine.

Drug: Sorafenib; Drug: Cytarabine; Drug: Clofarabine

Interventions

Sorafenib DRUG

Please see detailed description.

Also known as: Nexavar

Research Participants

Cytarabine DRUG

Please see Detailed Description.

Also known as: Cytosine Arabinoside

Research Participants

Clofarabine DRUG

Please see Detailed Description.

Also known as: Clolar

Research Participants

Eligibility Criteria

• Age: Up to 31 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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:
• First or greater relapse,
• Refractory to 1 or more courses of induction or reinduction chemotherapy, or
• 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:
• Hepatic:
• Serum direct bilirubin ≤2.0 mg/dl.
• Alanine transaminase (ALT/SGPT) ≤4 x ULN

You may not qualify if:

• 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.

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead
• National Cancer Institute (NCI): collaborator
• Bayer/Onyx: collaborator

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Myelodysplastic-Myeloproliferative Diseases; Leukemia, Promyelocytic, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Sorafenib; Cytarabine; Clofarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nucleotides; Ribonucleotides

Study Officials

• Hiroto Inaba, MD, PhD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2009
• First Posted: May 25, 2009
• Study Start: September 1, 2009
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: January 12, 2018

Record last verified: 2015-07

Locations

US (1)