LeukemiaPhase 1NCT00940524
Induction Therapy With Cytarabine, High-Dose Mitoxantrone and Dasatinib for Patients With Philadelphia-Chromosome Positive (Ph+) Acute Lymphoblastic Leukemia
A Phase 1 study testing Dasatinib, Mitoxantrone, Cytarabine in people with Leukemia and Acute Lymphoblastic Leukemia, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
Trial summary
This research study is for people with a specific type of leukemia called Philadelphia chromosome positive acute lymphoblastic leukemia (the type the patients have). The investigators plan to give you combination of 3 drugs (dasatinib, mitoxantrone, cytarabine) for the first part of the chemotherapy (called… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia, Acute Lymphoblastic Leukemia
- What is being tested?
- Dasatinib, Mitoxantrone, Cytarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2009to Apr 2014
- 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
- Previously untreated and treated adult patients (> or = 18 years old) with a diagnosis of:
- Philadelphia-chromosome positive acute lymphoblastic leukemia
- Lymphoid blast crisis of known chronic myelogenous leukemia NOTE: Patients must have evidence of a t(9;22) in leukemic cells based on chromosomal or molecular analysis.
- NOTE: The diagnosis must be confirmed by the pathology department at MSKCC. NOTE: It is recognized that newly diagnosed patients may be started on therapy with cytarabine and high-dose mitoxantrone (which is the standard of care at our institution for treating adult ALL) prior to the identification of t(9;22) in leukemic cells. These patients will remain eligible for participation on study and will be evaluable for response if it is possible to start treatment with dasatinib within 30 days of receiving induction chemotherapy.
- Patients with adequate hepatic function (AST and ALT < or = 2.5 the institutional ULN, bilirubin < or = 2.0 mg/dl).
- Patients with adequate renal function (creatinine < or = 2.0 mg/dl or creatinine clearance > 50 ml/min).
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- Patients with an LVEF > or = 50%.
- Karnofsky performance status > or = 20%.
- Ability to take oral medication (dasatinib must be swallowed whole).
- Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (sensitivity > or = 25IU HCG/L) within 72 hours prior to the start of study drug administration. Persons of reproductive potential must agree to use and utilize an adequate method of contraception throughout treatment and for at least 6 months after study drug is stopped. Prior to study enrollment, women of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy.
- concomitant Medications: Patient agrees to discontinue St. Johns Wort while receiving dasatinib therapy (discontinue St. Johns Wort at least 5 days before starting dasatinib); Patient agrees that IV bisphosphonates will be withheld for the first 8 weeks of dasatinib therapy due to risk of hypocalcemia.
- Signed informed consent, which indicates the investigational nature of this study, within 30 days of treatment initiation, is required.
Who cannot join
- Female patients who are pregnant or lactating. Women and men of childbearing age should use effective contraception.
- Patients with uncontrolled active infections.
- Patients who are receiving other systemic chemotherapy. Patients must have been off prior antileukemic therapy for at least 2 weeks (hydroxyurea is considered acceptable).
- NOTE: Patients who had previously received combination therapy with cytarabine, high-dose mitoxantrone and dasatinib will be excluded from the trial. All other prior therapies will be allowed, including prior tyrosine kinase inhibitors usage. Prior dasatinib use will be allowed (as a single agent or in combination therapy, other than the combination therapy with cytarabine and high-dose mitoxantrone).
- Concomitant active secondary malignancy requiring treatment (other than squamous cell and basal cell carcinoma of skin).
- Concurrent medical condition which may increase the risk of toxicity, including: grade ≥ 2 pleural or pericardial effusion.
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- Cardiac Symptoms; any of the following should be considered for exclusion:
- Uncontrolled angina, congestive heart failure or MI within (6 months).
- Diagnosed congenital long QT syndrome.
- Any history of clinically significant ventricular arrhythmias (such as ventricular - tachycardia, ventricular fibrillation, or Torsades de pointes).
- Prolonged QTc interval on pre-entry electrocardiogram (> 450 msec).
- Subjects with hypokalemia or hypomagnesemia if it cannot be corrected prior to dasatinib administration.
- History of significant bleeding disorder unrelated to cancer, including:
- Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease).
- Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies).
- Ongoing or recent (< or = 3 months) significant gastrointestinal bleeding
- Concomitant Medications, any of the following should be considered for exclusion:
- Category I drugs that are generally accepted to have a risk of causing Torsades de Pointes including: (Patients must discontinue drug 7 days prior to starting dasatinib)
- quinidine, procainamide, disopyramide amiodarone, sotalol, ibutilide, dofetilide erythromycin, clarithromycin chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine.
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: Phase I Study of Induction Therapy With Cytarabine, High-Dose Mitoxantrone and Dasatinib for Patients With Philadelphia-Chromosome Positive (Ph+) Acute Lymphoblastic Leukemia (ALL): ALL-6 Protocol
This research study is for people with a specific type of leukemia called Philadelphia chromosome positive acute lymphoblastic leukemia (the type the patients have). The investigators plan to give you combination of 3 drugs (dasatinib, mitoxantrone, cytarabine) for the first part of the chemotherapy (called Induction). The investigators have previously shown that the combination of mitoxantrone and cytarabine is very effective in your kind of leukemia. The purpose of this study is to establish a safe dose range of dasatinib in combination with this standard induction chemotherapy based on side effects. If possible, the trial will also give us an idea of how well this combination might work in treating your leukemia. Previous studies have shown that dasatinib can produce responses when given alone for your kind of leukemia. By using the dasatinib together with the chemotherapy, the investigators believe that we can kill even more leukemia cells than with either treatment alone. The investigators will initially treat patients with a low dose of dasatinib and monitor for side-effects. If the initial group of patients is able to tolerate this low-dose of dasatinib, then future patients will receive higher doses of dasatinib. Mitoxantrone and cytarabine chemotherapy is the standard therapy at the investigators' institution for the patient's leukemia and it is the combination of dasatinib with this chemotherapy that is new and investigational in this study.
- Conditions
- Leukemia, Acute Lymphoblastic Leukemia
- Being tested
- Dasatinib, Mitoxantrone, Cytarabine
- Keywords
- Leukemia, ALL, ALLOPURINOL, CARMUSTINE (BCNU), CYCLOPHOSPHAMIDE (CYTOXAN), CYTARABINE (ARA-C), DACTINOMYCIN, DASATINIB, DEXAMETHASONE, DOXORUBICIN/ADRIAMYCIN, ETOPOSIDE (VP-16), MERCAPTOPURINE, METHOTREXATE, MITOXANTRONE, PEGASPERGASE, VINCRISTINE
- Medical subject headings
- Leukemia, Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dasatinib, Mitoxantrone, CytarabineDrug
Also called CONSOLIDATION B-Dasatinib† (dose levels 1-3) *continuously, Cyclophosphamide 4 g/m2 IV (age > or = 60 yrs 3 g/m2), Myeloid growth factor on day 7 until ANC > 1,000/μl x 2 days, CONSOLIDATION C-Dasatinib† (dose levels 1-3) *continuously
INDUCTION- Dasatinib† (dose levels 1-3) *continuously Cytarabine 3 g/m2 IV over 3 hours Mitoxantrone 80 mg/m2 IV Myeloid growth factor on day 7 until ANC > 1,000/μl x 2 days Allopurinol 300 mg BID-TID x 7 days (starting 6-12 hours prior to chemotherapy) Dexamethasone 0.1% eye drops q6h while on cytarabine (start prior to the first dose of cytarabine and continuing at least 24 hours after the last dose) IT Methotrexate 12 mg days 2 and 4
CONSOLIDATION A-Dasatinib† (dose levels 1-3) *continuously Vincristine 2 mg IV Dexamethasone 10 mg/m2/d days 2 to 29, then taper over 10 days Sulfamethoxazole/Trimethoprim 1 DS BID three times weekly days 2 to 29, then BID daily days 30 to 45 IT Methotrexate 12 mg days 8, 15, 22 and 29
| Study group | Role | What they receive |
|---|---|---|
| Chemotherapy | Experimental | A phase I study designed to determine the dose of dasatinib that can be safely administered with cytarabine and high-dose mitoxantrone in Ph+ ALL / lymphoid blast crisis of known chronic myelogenous leukemia patients. Receives: Drug: Dasatinib, Mitoxantrone, Cytarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the dose of dasatinib that can be safely administered with cytarabine, and high-dose mitoxantrone in patients with Ph+ ALL / lymphoid blast crisis of known chronic myelogenous leukemia.
Measured: 5 years
Secondary outcomes (2)
To determine the toxicity of this combination in these patients.
Measured: 5 years
To determine Abl-mutational status at baseline and at the time of disease progression as a possible mechanism of resistance.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2009 (estimated)
- Study startJul 2009
- Primary completionApr 2014
- Study completionApr 2014
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
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Renier Brentjens, MD, PhD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00940524
- Sponsor's protocol ID
- 09-046
- Status last verified
- Apr 2014
- First submitted
- 14 Jul 2009
- Last updated
- 10 Apr 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Induction Therapy With Cytarabine, High-Dose Mitoxantrone and Dasatinib for Patients With Philadelphia-Chromosome Positive (Ph+) Acute Lymphoblastic Leukemia (ALL): ALL-6 Protocol
- ClinicalTrials.gov ID
- NCT00940524
- Acronym / sponsor ID
- 09-046
- Conditions
- Leukemia, Acute Lymphoblastic Leukemia
- Keywords
- Leukemia, ALL, ALLOPURINOL, CARMUSTINE (BCNU), CYCLOPHOSPHAMIDE (CYTOXAN), CYTARABINE (ARA-C), DACTINOMYCIN, DASATINIB
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- Jul 2009
- Primary completion
- Apr 2014 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 16 Jul 2009 (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 research study is for people with a specific type of leukemia called Philadelphia chromosome positive acute lymphoblastic leukemia (the type the patients have). The investigators plan to give you combination of 3 drugs (dasatinib, mitoxantrone, cytarabine) for the first part of the chemotherapy (called Induction). The investigators have previously shown that the combination of mitoxantrone and cytarabine is very effective in your kind of leukemia. The purpose of this study is to establish a safe dose range of dasatinib in combination with this standard induction chemotherapy based on side effects. If possible, the trial will also give us an idea of how well this combination might work in treating your leukemia. Previous studies have shown that dasatinib can produce responses when given alone for your kind of leukemia. By using the dasatinib together with the chemotherapy, the investigators believe that we can kill even more leukemia cells than with either treatment alone. The investigators will initially treat patients with a low dose of dasatinib and monitor for side-effects. If the initial group of patients is able to tolerate this low-dose of dasatinib, then future patients will receive higher doses of dasatinib. Mitoxantrone and cytarabine chemotherapy is the standard therapy at the investigators' institution for the patient's leukemia and it is the combination of dasatinib with this chemotherapy that is new and investigational in 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 |
|---|---|---|
| Chemotherapy | Experimental | Drug: Dasatinib, Mitoxantrone, CytarabineA phase I study designed to determine the dose of dasatinib that can be safely administered with cytarabine and high-dose mitoxantrone in Ph+ ALL / lymphoid blast crisis of known chronic myelogenous leukemia patients. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Previously untreated and treated adult patients (> or = 18 years old) with a diagnosis of:
- NOTE: The diagnosis must be confirmed by the pathology department at MSKCC. NOTE: It is recognized that newly diagnosed patients may be started on therapy with cytarabine and high-dose mitoxantrone (which is the standard of care at our institution for treating adult ALL) prior to the identification of t(9;22) in leukemic cells. These patients will remain eligible for participation on study and will be evaluable for response if it is possible to start treatment with dasatinib within 30 days of receiving induction chemotherapy.
- Patients with adequate hepatic function (AST and ALT < or = 2.5 the institutional ULN, bilirubin < or = 2.0 mg/dl).
- Patients with adequate renal function (creatinine < or = 2.0 mg/dl or creatinine clearance > 50 ml/min).
- Patients with an LVEF > or = 50%.
Key exclusion criteria (19 listed)
- Female patients who are pregnant or lactating. Women and men of childbearing age should use effective contraception.
- Patients with uncontrolled active infections.
- Patients who are receiving other systemic chemotherapy. Patients must have been off prior antileukemic therapy for at least 2 weeks (hydroxyurea is considered acceptable).
- NOTE: Patients who had previously received combination therapy with cytarabine, high-dose mitoxantrone and dasatinib will be excluded from the trial. All other prior therapies will be allowed, including prior tyrosine kinase inhibitors usage. Prior dasatinib use will be allowed (as a single agent or in combination therapy, other than the combination therapy with cytarabine and high-dose mitoxantrone).
- Concomitant active secondary malignancy requiring treatment (other than squamous cell and basal cell carcinoma of skin).
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 |
|---|---|---|
| Dasatinib, Mitoxantrone, CytarabineAlso: CONSOLIDATION B-Dasatinib† (dose levels 1-3) *continuously, Cyclophosphamide 4 g/m2 IV (age > or = 60 yrs 3 g/m2), Myeloid growth factor on day 7 until ANC > 1,000/μl x 2 days, CONSOLIDATION C-Dasatinib† (dose levels 1-3) *continuouslyINDUCTION- Dasatinib† (dose levels 1-3) *continuously Cytarabine 3 g/m2 IV over 3 hours Mitoxantrone 80 mg/m2 IV Myeloid growth factor on day 7 until ANC > 1,000/μl x 2 days Allopurinol 300 mg BID-TID x 7 days (starting 6-12 hours prior to chemotherapy) Dexamethasone 0.1% eye drops q6h while on cytarabine (start prior to the first dose of cytarabine and continuing at least 24 hours after the last dose) IT Methotrexate 12 mg days 2 and 4 CONSOLIDATION A-Dasatinib† (dose levels 1-3) *continuously Vincristine 2 mg IV Dexamethasone 10 mg/m2/d days 2 to 29, then taper over 10 days Sulfamethoxazole/Trimethoprim 1 DS BID three times weekly days 2 to 29, then BID daily days 30 to 45 IT Methotrexate 12 mg days 8, 15, 22 and 29 | Drug | Chemotherapy |
Primary outcome
To determine the dose of dasatinib that can be safely administered with cytarabine, and high-dose mitoxantrone in patients with Ph+ ALL / lymphoid blast crisis of known chronic myelogenous leukemia.
Time frame: 5 years
2 secondary outcomes
To determine the toxicity of this combination in these patients.
Time frame: 5 years
To determine Abl-mutational status at baseline and at the time of disease progression as a possible mechanism of resistance.
Time frame: 5 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 10 Apr 2014.
- Memorial Sloan-Kettering Cancer CenterLink provided by the sponsor.
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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.
Renier Brentjens, MD, PhD 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 Dasatinib, Mitoxantrone, Cytarabine in people with Leukemia and Acute Lymphoblastic 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?
The sponsor lists 12 inclusion and 19 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 10 Apr 2014. 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 determine the dose of dasatinib that can be safely administered with cytarabine, and high-dose mitoxantrone in patients with Ph+ ALL / lymphoid blast crisis of known chronic myelogenous leukemia. (time frame: 5 years). 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 10 Apr 2014.