Adult Acute Basophilic LeukemiaPhase 1NCT00131989
Sorafenib in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Chronic Myelogenous Leukemia
A Phase 1 study testing sorafenib tosylate, pharmacological study and laboratory biomarker analysis in people with Adult Acute Basophilic Leukemia and Adult Acute Eosinophilic Leukemia, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This phase I trial is studying the side effects and best dose of sorafenib in treating patients with relapsed or refractory acute myeloid leukemia, acute lymphoblastic leukemia, or chronic myelogenous leukemia. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adult Acute Basophilic Leukemia, Adult Acute Eosinophilic Leukemia, Adult Acute Megakaryoblastic Leukemia (M7)
- What is being tested?
- sorafenib tosylate, pharmacological study and laboratory biomarker analysis
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2005to Apr 2007
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have pathological confirmation (histologically or cytologically) of relapsed or refractory acute myeloid leukemia (other than acute promyelocytic leukemia), acute lymphocytic leukemia, or chronic myeloid leukemia in blast crisis
- The morphologic diagnosis of AML (non-APL), ALL, and CML in blast crisis will be made independently by members of the hematologic pathology division; routine staining and standard criteria as outlined by the Report of the NCI-Sponsored Workshop will be followed
- All patients must have been refractory to or relapsed from their most recent therapy AND are considered ineligible for potential curative approaches including allogeneic stem cell transplant; in addition, patients must be at least:
- 3 weeks from last cytotoxic chemotherapy (excluding hydroxyurea)
- Hydroxyurea may be used for blast count control but must be discontinued within 48 hours of the initiation of BAY 43-9006
- 2 weeks from last radiation therapy
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- 3 week from last biologic therapy (including myeloid growth factors)
- ECOG performance status =< 2 (Karnofsky >= 60%)
- Life expectancy of greater than 2 months
- Multilineage bone marrow failure due to the subject's underlying leukemia
- Total blast count in the peripheral blood < 30,000
- Total bilirubin =< 2 mg/dl
- AST(SGOT)/ALT(SGPT) =< 5 X institutional upper limit of normal
- Serum creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- All women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; the effects of BAY 43-9006 on the developing human fetus at the recommended therapeutic dose are unknown; however, kinase inhibitors are known to be teratogenic; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- Ability to understand and the willingness to sign a written informed consent document
Who cannot join
- Patients with APL are not eligible for this clinical trial
- Patients who have not recovered from adverse events due to agents administered more than 3 weeks earlier
- Patients with rapidly increasing peripheral blood blast counts (increase in the absolute peripheral blast count > 50% within one week) or uncontrolled (absolute blast count > 30,000) while on hydroxyurea will be excluded
- Patients with uncontrolled hypertension (i.e., persistent grade 3 while undergoing treatment)
- Patients may not be actively receiving any other investigational agents
- Patients active and / or untreated CNS leukemia will not be eligible
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- History of allergic reactions attributed to compounds of similar chemical or biologic composition to BAY 43-9006
- Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with BAY 43-9006
- Patients with immune deficiency are at increased risk of lethal infections when treated with marrow suppressive therapy; therefore, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with BAY 43-9006; appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Patients must not have any evidence of bleeding diathesis
- Patients must not be on therapeutic anticoagulation; prophylactic anticoagulation (i.e. low dose warfarin) of venous or arterial access devices is allowed provided that the requirements for PT, INR or PTT are met
- Patients must not be taking the cytochrome P450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine, or phenobarbital), rifampin or St. John's wort
Trial locations and contacts
1 site in 1 country.
United States1 site
Johns Hopkins University
Baltimore, Maryland, 21287-8936
About this study
Official title: Phase I Dose Escalation Trial of the Raf Kinase Inhibitor BAY 43-9006 (NSC #724772) as Single Agent for Adults With Relapsed and Refractory Acute Leukemias and Chronic Myeloid Leukemia in Blast Crisis
This phase I trial is studying the side effects and best dose of sorafenib in treating patients with relapsed or refractory acute myeloid leukemia, acute lymphoblastic leukemia, or chronic myelogenous leukemia. Sorafenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the dose-limiting toxicity(s) (DLTs) and maximally tolerated dose (MTD) of BAY 43-9006 given orally.
SECONDARY OBJECTIVES:
- To obtain preliminary evidence of tumor response to BAY 43-9006 in patients. II. To assess the pharmacokinetic profile of BAY 43-9006. III. To characterize the preliminary profile of adverse events and changes in laboratory parameters in patients treated with BAY 43-9006.
IV. To assess effects of BAY 43-9006 on various cellular properties of leukemic blasts exposed to drug in vivo and in vitro.
OUTLINE: This is an open-label, dose-escalation study.
Patients receive oral sorafenib twice daily on days 1-14 or 1-21. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a complete remission (CR) may be considered for retreatment with sorafenib for up to an additional 6 courses upon disease recurrence provided the duration of CR is longer than 1 month.
Cohorts of 3-6 patients receive escalating doses of sorafenib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. A total of 12 patients are treated at the MTD.
After completion of study treatment, patients are followed monthly for up to 1 year.
- Conditions
- Adult Acute Basophilic Leukemia, Adult Acute Eosinophilic Leukemia, Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monocytic Leukemia (M5b), Adult Acute Myeloblastic Leukemia With Maturation (M2)
- Being tested
- sorafenib tosylate, pharmacological study, laboratory biomarker analysis
- Medical subject headings
- Leukemia, Basophilic, Acute, Leukemia, Eosinophilic, Acute, Leukemia, Megakaryoblastic, Acute, Leukemia, Monocytic, Acute, Leukemia, Myeloid, Acute, Congenital Abnormalities, Leukemia, Myelomonocytic, Acute, Leukemia, Erythroblastic, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sorafenib tosylateDrug
Also called BAY 43-9006, BAY 43-9006 Tosylate Salt, BAY 54-9085, Nexavar
Given orally
Also called pharmacological studies
Correlative studies
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (sorafenib tosylate) | Experimental | Patients receive oral sorafenib twice daily on days 1-14 or 1-21. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a CR may be considered for retreatment with sorafenib for up to an additional 6 courses upon disease recurrence provided the duration of CR is longer than 1 month. Receives: Drug: sorafenib tosylate; Other: pharmacological study; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
DLT defined as non-hematologic > grade 3 or hematologic grade 4 marrow aplasia > 28 days (without leukemia clearance) as assessed by NCI-CTC version 3.0
Observed toxicities will be reported and summarized s with frequencies, type and grade in a descriptive manner. No formal statistical inference will be made on this dose-finding study.
Measured: 28 days
MDT based on the incidence of DTL as assessed by NCI-CTC version 3.0
Observed toxicities will be reported and summarized s with frequencies, type and grade in a descriptive manner. No formal statistical inference will be made on this dose-finding study.
Measured: 28 days
Secondary outcomes (4)
Response (CR and/or PR)
Summarized in different dose levels and durations. The 95% confidence intervals will be provided.
Measured: Up to 1 year
Pharmacokinetic parameters
Pharmacokinetic parameters over time in different dose levels will be evaluated via descriptive statistics.
Measured: At baseline, at 0.25, 0.5, 1, 2, 4, 6, 8, 24, and 48 hours (days 1, 2, and 3) at days 8, 15, and 29
Sorafenib tosylate related adverse events as assessed by NCI-CTC version 3.0
Adverse events will be summarized with frequencies by type and grade in different dose levels and durations using descriptive statistics.
Measured: Up to 1 year after completion of treatment
Impact of sorafenib tosylate on the Raf kinase/MEK/ERK signaling pathway
Mean percentage changes will be estimated along with 95% confidence intervals. Dichotomous outcome (on/off) will be tabulated and proportions of activation between pre and post treatment will be compared using Fisher's exact test for each of those targets involved in Raf kinase signaling pathway.
Measured: At baseline and at 28 days (course 1)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2005 (estimated)
- Study startJun 2005
- Primary completionApr 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Adult Acute Basophilic LeukemiaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- B. Smith, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00131989
- Sponsor's protocol ID
- NCI-2012-03154
- Other IDs
- J-0509, U01CA070095
- Status last verified
- Jan 2013
- First submitted
- 16 Aug 2005
- Last updated
- 9 Jan 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Dose Escalation Trial of the Raf Kinase Inhibitor BAY 43-9006 (NSC #724772) as Single Agent for Adults With Relapsed and Refractory Acute Leukemias and Chronic Myeloid Leukemia in Blast Crisis
- ClinicalTrials.gov ID
- NCT00131989
- Acronym / sponsor ID
- NCI-2012-03154
- Conditions
- Adult Acute Basophilic Leukemia, Adult Acute Eosinophilic Leukemia, Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monocytic Leukemia (M5b), Adult Acute Myeloblastic Leukemia With Maturation (M2)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Jun 2005
- Primary completion
- Apr 2007 (actual)
- First posted
- 19 Aug 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase I trial is studying the side effects and best dose of sorafenib in treating patients with relapsed or refractory acute myeloid leukemia, acute lymphoblastic leukemia, or chronic myelogenous leukemia. Sorafenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer
Detailed description
PRIMARY OBJECTIVES:
- To determine the dose-limiting toxicity(s) (DLTs) and maximally tolerated dose (MTD) of BAY 43-9006 given orally.
SECONDARY OBJECTIVES:
- To obtain preliminary evidence of tumor response to BAY 43-9006 in patients. II. To assess the pharmacokinetic profile of BAY 43-9006. III. To characterize the preliminary profile of adverse events and changes in laboratory parameters in patients treated with BAY 43-9006.
IV. To assess effects of BAY 43-9006 on various cellular properties of leukemic blasts exposed to drug in vivo and in vitro.
OUTLINE: This is an open-label, dose-escalation study.
Patients receive oral sorafenib twice daily on days 1-14 or 1-21. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a complete remission (CR) may be considered for retreatment with sorafenib for up to an additional 6 courses upon disease recurrence provided the duration of CR is longer than 1 month.
Cohorts of 3-6 patients receive escalating doses of sorafenib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. A total of 12 patients are treated at the MTD.
After completion of study treatment, patients are followed monthly for up to 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (sorafenib tosylate) | Experimental | Drug: sorafenib tosylate, Other: pharmacological study, Other: laboratory biomarker analysisPatients receive oral sorafenib twice daily on days 1-14 or 1-21. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a CR may be considered for retreatment with sorafenib for up to an additional 6 courses upon disease recurrence provided the duration of CR is longer than 1 month. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Patients must have pathological confirmation (histologically or cytologically) of relapsed or refractory acute myeloid leukemia (other than acute promyelocytic leukemia), acute lymphocytic leukemia, or chronic myeloid leukemia in blast crisis
- The morphologic diagnosis of AML (non-APL), ALL, and CML in blast crisis will be made independently by members of the hematologic pathology division; routine staining and standard criteria as outlined by the Report of the NCI-Sponsored Workshop will be followed
- All patients must have been refractory to or relapsed from their most recent therapy AND are considered ineligible for potential curative approaches including allogeneic stem cell transplant; in addition, patients must be at least:
- ECOG performance status =< 2 (Karnofsky >= 60%)
- Life expectancy of greater than 2 months
Key exclusion criteria (13 listed)
- Patients with APL are not eligible for this clinical trial
- Patients who have not recovered from adverse events due to agents administered more than 3 weeks earlier
- Patients with rapidly increasing peripheral blood blast counts (increase in the absolute peripheral blast count > 50% within one week) or uncontrolled (absolute blast count > 30,000) while on hydroxyurea will be excluded
- Patients with uncontrolled hypertension (i.e., persistent grade 3 while undergoing treatment)
- Patients may not be actively receiving any other investigational agents
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sorafenib tosylateAlso: BAY 43-9006, BAY 43-9006 Tosylate Salt, BAY 54-9085, NexavarGiven orally | Drug | Treatment (sorafenib tosylate) |
| pharmacological studyAlso: pharmacological studiesCorrelative studies | Other | Treatment (sorafenib tosylate) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (sorafenib tosylate) |
Primary outcome
DLT defined as non-hematologic > grade 3 or hematologic grade 4 marrow aplasia > 28 days (without leukemia clearance) as assessed by NCI-CTC version 3.0
Time frame: 28 days
Observed toxicities will be reported and summarized s with frequencies, type and grade in a descriptive manner. No formal statistical inference will be made on this dose-finding study.
MDT based on the incidence of DTL as assessed by NCI-CTC version 3.0
Time frame: 28 days
Observed toxicities will be reported and summarized s with frequencies, type and grade in a descriptive manner. No formal statistical inference will be made on this dose-finding study.
4 secondary outcomes
Response (CR and/or PR)
Time frame: Up to 1 year
Pharmacokinetic parameters
Time frame: At baseline, at 0.25, 0.5, 1, 2, 4, 6, 8, 24, and 48 hours (days 1, 2, and 3) at days 8, 15, and 29
Sorafenib tosylate related adverse events as assessed by NCI-CTC version 3.0
Time frame: Up to 1 year after completion of treatment
Impact of sorafenib tosylate on the Raf kinase/MEK/ERK signaling pathway
Time frame: At baseline and at 28 days (course 1)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
B. Smith principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing sorafenib tosylate, pharmacological study and laboratory biomarker analysis in people with Adult Acute Basophilic Leukemia and Adult Acute Eosinophilic Leukemia, run by National Cancer Institute (NCI) 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 16 inclusion and 13 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 9 Jan 2013. 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?
DLT defined as non-hematologic > grade 3 or hematologic grade 4 marrow aplasia > 28 days (without leukemia clearance) as assessed by NCI-CTC version 3.0 (time frame: 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Jan 2013.