AzTrials
AzTrials

Acute Myeloid LeukemiaPhase 1NCT00908167

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

A Phase 1 study testing Sorafenib, Cytarabine and Clofarabine in people with Acute Myeloid Leukemia and Infantile Leukemia (Both AML and ALL), run by St. Jude Children's Research Hospital at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages Up to 31 years
What is being tested?
Sorafenib, Cytarabine and Clofarabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
44 participants
Where
1 siteUnited States
Study dates
Sep 2009to Jun 2015
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 31 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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).
Show all 24Show fewer
  • 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
  • Cardiovascular:
  • Shortening fraction of greater than or equal to 25% by echocardiogram
  • Pulmonary:
  • Pulse oximetry ≥93% at room air
  • Renal:
  • Creatinine clearance or radioisotope GFR greater than or equal to 70 mL/min/1.73m2 or serum creatinine based on age
  • 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.

Who cannot join

  • 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. .
Show all 31Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • St. Jude Children's Research Hospital

    Memphis, Tennessee, 38105

Other trials in United States

About this study

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

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.

Read the 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).

Being tested
Sorafenib, Cytarabine, Clofarabine
Keywords
sorafenib, cytarabine, clofarabine, acute myeloid leukemia, acute promyelocytic leukemia, acute lymphoblastic leukemia
Medical subject headings
Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Myelodysplastic-Myeloproliferative Diseases, Leukemia, Promyelocytic, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SorafenibDrug

    Also called Nexavar

    Please see detailed description.

  • CytarabineDrug

    Also called Cytosine Arabinoside

    Please see Detailed Description.

  • ClofarabineDrug

    Also called Clolar

    Please see Detailed Description.

Study groups in NCT00908167
Study groupRoleWhat they receive
Research ParticipantsOtherParticipants treated with sorafenib, cytarabine and clofarabine.
Receives: Drug: Sorafenib; Drug: Cytarabine; Drug: Clofarabine

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: 4.5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 May 2009 (estimated)
  2. Study startSep 2009
  3. Primary completionJun 2015
  4. Study completionJun 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
44 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00908167
Sponsor's protocol ID
RELHEM
Other IDs
R01CA138744, NCI-2011-01252
Status last verified
Jul 2015
First submitted
21 May 2009
Last updated
12 Jan 2018
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Sorafenib, Cytarabine and Clofarabine in people with Acute Myeloid Leukemia and Infantile Leukemia (Both AML and ALL), run by St. Jude Children's Research Hospital at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00908167.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jan 2018.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in