LeukemiaPhase 1NCT00462787
Combination Chemotherapy in Treating Young Patients With Relapsed or Refractory Acute Leukemia
A Phase 1 study testing filgrastim, clofarabine and dexamethasone in people with Leukemia, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as clofarabine, topotecan, vinorelbine, thiotepa, and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. Read more about this study
- Who is it for?
- Ages Up to 28 years
- Conditions the study is for
- Leukemia
- What is being tested?
- filgrastim, clofarabine and dexamethasone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2007to Nov 2013
- 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 28 years
- All sexes
- No healthy volunteers
- Child, Adult
DISEASE CHARACTERISTICS:
- Must have 1 of the following diagnoses:
- Acute lymphoblastic leukemia (ALL) meeting 1 of the following criteria:
- Refractory to initial induction with two or more standard regimens
- Relapsed < 24 months after first complete response on a high-risk protocol OR refractory to one standard reinduction regimen
- Second or greater relapse
- Acute myeloid leukemia, acute biphenotypic leukemia, or acute undifferentiated leukemia meeting 1 of the following criteria:
- Refractory to initial induction
- First or greater relapse
- Must have > 20% bone marrow blasts, or evidence of recurrent disease at an extramedullary site
- No symptomatic CNS disease
- Patients with asymptomatic CNS disease are eligible with the approval of the principal investigator
PATIENT CHARACTERISTICS:
- Karnofsky performance status (PS) 70-100% OR Lansky PS 70-100%
- AST and ALT < 4 times upper limit of normal
- Bilirubin < 2.0 mg/dL (unless liver involvement)
- Creatinine within normal range for age OR creatinine clearance > 60 mL/min/1.73 m^2
- Adequate cardiac function (either asymptomatic with no prior risk factors, or if symptomatic, left ventricular ejection fraction > 50% at rest)
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No active uncontrolled viral, bacterial, or fungal infection
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior clofarabine
- More than 2 weeks since prior systemic chemotherapy
- At least 7 days since prior chemotherapy for patients with rapidly progressive disease and recovered
Trial locations and contacts
1 site in 1 country.
United States1 site
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
About this study
Official title: A Phase I Dose Escalation Trial of Clofarabine in Addition to Topotecan, Vinorelbine, Thiotepa, and Dexamethasone in Pediatric Patients With Relapsed or Refractory Acute Leukemia
RATIONALE: Drugs used in chemotherapy, such as clofarabine, topotecan, vinorelbine, thiotepa, and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and best dose of clofarabine when given together with topotecan, vinorelbine, thiotepa, and dexamethasone in treating young patients with relapsed or refractory acute leukemia.
Read the detailed description
OBJECTIVES:
- Determine the maximum tolerated dose of clofarabine when administered in combination with topotecan hydrochloride, vinorelbine ditartrate, thiotepa, and dexamethasone in young patients with relapsed or refractory acute leukemia.
- Evaluate the antileukemic potential of this regimen in these patients.
- Evaluate the incidence and severity of treatment-related morbidity and mortality in patients treated with this regimen.
- Develop a new reinduction treatment regimen that will result in a patient clinical response with as little residual disease as possible to permit a bone marrow transplantation while in subsequent remission; maintain the response long enough to identify an appropriate stem cell donor; and permit the patient to undergo a stem cell transplantation free of infections and without vital organ dysfunction.
OUTLINE: This is a nonrandomized, prospective, dose-escalation study of clofarabine.
Patients receive topotecan hydrochloride IV continuously over 120 hours on days 0-4; vinorelbine ditartrate over 6-10 minutes on days 0, 7, and 14; thiotepa IV over 4 hours on day 2; clofarabine IV over 2 hours on days 3-7; and oral or IV dexamethasone 3 times daily on days 3 and 7-13 and then on day 3 only thereafter. Patients also receive filgrastim (G-CSF) subcutaneously once daily beginning on day 8 and continuing until blood counts recover. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of clofarabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 6 patients experience dose-limiting toxicity OR the dose preceding that at which 2 of 3 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.
After completion of study treatment, patients are followed once a week for 4 weeks, twice a month for 6 months, and then once a month for 2 years.
PROJECTED ACCRUAL: A total of 23 patients will be accrued for this study.
- Conditions
- Leukemia
- Being tested
- filgrastim, clofarabine, dexamethasone, thiotepa, topotecan hydrochloride
- Keywords
- acute undifferentiated leukemia, recurrent childhood acute lymphoblastic leukemia, recurrent childhood acute myeloid leukemia, recurrent adult acute lymphoblastic leukemia, recurrent adult acute myeloid leukemia
- Medical subject headings
- Leukemia, Leukemia, Biphenotypic, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
filgrastimBiological
clofarabineDrug
dexamethasoneDrug
thiotepaDrug
topotecan hydrochlorideDrug
vinorelbine tartrateDrug
| Study group | Role | What they receive |
|---|---|---|
| Clofarabine | Experimental | This is a single arm phase I clinical trial to assess safety (morbidity and mortality) of a novel leukemia re-induction regimen. The first component of this trial is a phase I dose escalation study to determine the maximum tolerated dose (MTD) of the novel agent Clofarabine, when used in combination with topotecan, vinorelbine, thiotepa and dexamethasone. A total of three dose levels will be explored in this study. Receives: Biological: filgrastim; Drug: clofarabine; Drug: dexamethasone; Drug: thiotepa; Drug: topotecan hydrochloride; Drug: vinorelbine tartrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose of clofarabine
Measured: 2 years
Overall survival
Measured: 2 years
Progression-free survival
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2007 (estimated)
- Study startApr 2007
- Primary completionNov 2013
- Study completionNov 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe 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
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Peter G. Steinherz, MD, Principal investigator, Memorial Sloan Kettering Cancer CenterNeerav Shukla, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00462787
- Sponsor's protocol ID
- 07-012
- Other IDs
- MSKCC-07012
- Status last verified
- Nov 2013
- First submitted
- 18 Apr 2007
- Last updated
- 14 Nov 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Dose Escalation Trial of Clofarabine in Addition to Topotecan, Vinorelbine, Thiotepa, and Dexamethasone in Pediatric Patients With Relapsed or Refractory Acute Leukemia
- ClinicalTrials.gov ID
- NCT00462787
- Acronym / sponsor ID
- 07-012
- Conditions
- Leukemia
- Keywords
- acute undifferentiated leukemia, recurrent childhood acute lymphoblastic leukemia, recurrent childhood acute myeloid leukemia, recurrent adult acute lymphoblastic leukemia, recurrent adult acute myeloid leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Apr 2007
- Primary completion
- Nov 2013 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 19 Apr 2007 (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.
RATIONALE: Drugs used in chemotherapy, such as clofarabine, topotecan, vinorelbine, thiotepa, and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and best dose of clofarabine when given together with topotecan, vinorelbine, thiotepa, and dexamethasone in treating young patients with relapsed or refractory acute leukemia.
Detailed description
OBJECTIVES:
- Determine the maximum tolerated dose of clofarabine when administered in combination with topotecan hydrochloride, vinorelbine ditartrate, thiotepa, and dexamethasone in young patients with relapsed or refractory acute leukemia.
- Evaluate the antileukemic potential of this regimen in these patients.
- Evaluate the incidence and severity of treatment-related morbidity and mortality in patients treated with this regimen.
- Develop a new reinduction treatment regimen that will result in a patient clinical response with as little residual disease as possible to permit a bone marrow transplantation while in subsequent remission; maintain the response long enough to identify an appropriate stem cell donor; and permit the patient to undergo a stem cell transplantation free of infections and without vital organ dysfunction.
OUTLINE: This is a nonrandomized, prospective, dose-escalation study of clofarabine.
Patients receive topotecan hydrochloride IV continuously over 120 hours on days 0-4; vinorelbine ditartrate over 6-10 minutes on days 0, 7, and 14; thiotepa IV over 4 hours on day 2; clofarabine IV over 2 hours on days 3-7; and oral or IV dexamethasone 3 times daily on days 3 and 7-13 and then on day 3 only thereafter. Patients also receive filgrastim (G-CSF) subcutaneously once daily beginning on day 8 and continuing until blood counts recover. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of clofarabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 6 patients experience dose-limiting toxicity OR the dose preceding that at which 2 of 3 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.
After completion of study treatment, patients are followed once a week for 4 weeks, twice a month for 6 months, and then once a month for 2 years.
PROJECTED ACCRUAL: A total of 23 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Clofarabine | Experimental | Biological: filgrastim, Drug: clofarabine, Drug: dexamethasone, Drug: thiotepa, Drug: topotecan hydrochloride, Drug: vinorelbine tartrateThis is a single arm phase I clinical trial to assess safety (morbidity and mortality) of a novel leukemia re-induction regimen. The first component of this trial is a phase I dose escalation study to determine the maximum tolerated dose (MTD) of the novel agent Clofarabine, when used in combination with topotecan, vinorelbine, thiotepa and dexamethasone. A total of three dose levels will be explored in this study. |
Who may qualify
- Ages
- Up to 28 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
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 |
|---|---|---|
| filgrastim | Biological | Clofarabine |
| clofarabine | Drug | Clofarabine |
| dexamethasone | Drug | Clofarabine |
| thiotepa | Drug | Clofarabine |
| topotecan hydrochloride | Drug | Clofarabine |
| vinorelbine tartrate | Drug | Clofarabine |
Primary outcome
Maximum tolerated dose of clofarabine
Time frame: 2 years
Overall survival
Time frame: 2 years
Progression-free survival
Time frame: 2 years
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 14 Nov 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.
Peter G. Steinherz, MD principal investigator
Memorial Sloan Kettering Cancer Center
Neerav Shukla, MD principal investigator
Memorial Sloan Kettering Cancer Center
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 filgrastim, clofarabine and dexamethasone in people with Leukemia, run by Memorial Sloan Kettering Cancer Center 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?
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 14 Nov 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?
Maximum tolerated dose of clofarabine (time frame: 2 years). The study lists 3 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 14 Nov 2013.