Adult Acute Basophilic LeukemiaPhase 2NCT00407966
Alvocidib, Cytarabine, and Mitoxantrone in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia
A Phase 2 study testing alvocidib, cytarabine and mitoxantrone hydrochloride 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 II trial is studying the side effects and how well giving alvocidib together with cytarabine and mitoxantrone works in treating patients with newly diagnosed acute myeloid 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?
- alvocidib, cytarabine and mitoxantrone hydrochloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2006to Nov 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Adults with established, pathologically confirmed diagnoses of newly diagnosed, poor-risk Acute Myeloid Leukemia(AML) including de novo and secondary Acute Myeloid Leukemias but excluding newly diagnosed acute progranulocytic leukemia (APL, M3) will be considered eligible for study
- ECOG performance status 0-2
- Patient must be able to give informed consent
- Serum creatinine =< 2.0
- ALT, AST =< 5 x upper limit of normal
- Bilirubin =< 2.0 mg/dl
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- Left ventricular ejection fraction >= 45%
- Newly diagnosed AML, subtypes M0,1,2,4-7 but excluding M3 (APL) with poor-risk features, including:
- Age > 50 years, or age > 18 years with one or more of the following criteria:
- Antecedent hematologic disorder including myelodysplasia (MDS)-related AML (MDS/AML) and prior myeloproliferative disorder (MPD)
- Treatment-related AML
- AML with trilineage dysplasia (AML-TLD)
- Adverse cytogenetics (defined as -5/-5q; -7/-7q; abnormal 3q, 9q, 11q, 20q, 21q or 17p; t(6;9); t(9;22); trisomy 8; trisomy 13, complex karyotypes (>= 3 unrelated abnormalities)
Who cannot join
- Patients who have received hydroxyurea alone or have received non-cytotoxic therapies previously for MDS or MPD (e.g., thalidomide or lenalidomide, interferon, cytokines, low-dose 5-azacytidine, low-dose cytoxan) will be eligible for this trial
- Any previous treatment with flavopiridol
- Concomitant chemotherapy, radiation therapy, or immunotherapy
- Hyperleukocytosis with >= 50,000 blasts/uL; leukapheresis or hydroxyurea may be used immediately prior to study drug administration for cytoreduction; must be stopped 24 hours before first dose of Flavopiridol
- Acute Progranulocytic Leukemia (APL, M3)
- Active CNS leukemia
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- Active, uncontrolled infection; patients with infection under active treatment and controlled with antibiotics are eligible
- Presence of other life-threatening illness
- Patients with mental deficits and/or psychiatric history that preclude them form giving informed consent or from following protocol
- Pregnant and nursing patients are excluded
Trial locations and contacts
1 site in 1 country.
United States1 site
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
About this study
Official title: Phase II Study of Alvocidib (NSC 649890, Flavopiridol) in Timed Sequential Combination With Cytosine Arabinoside (Ara-C) and Mitoxantrone for Adults With Newly Diagnosed, Previously Untreated, Poor-Risk Acute Myelogenous Leukemias
This phase II trial is studying the side effects and how well giving alvocidib together with cytarabine and mitoxantrone works in treating patients with newly diagnosed acute myeloid leukemia. Drugs used in chemotherapy, such as alvocidib, cytarabine, and mitoxantrone, 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 the detailed description
PRIMARY OBJECTIVES:
- To determine the efficacy and toxicities of flavopiridol (alvocidib) followed by ara-C and mitoxantrone in adults with newly diagnosed acute myelogenous leukemia (AML) with poor-risk features.
II. To determine the disease free and overall survival of patients exhibiting a response to treatment with flavopiridol followed by ara-C and mitoxantrone.
OUTLINE:
Patients receive alvocidib IV over 1 hour on days 1-3, cytarabine IV continuously over 72 hours on days 6-8, and mitoxantrone hydrochloride IV over 1-2 hours on day 9. Beginning 35-63 days after completion of course 1, patients achieving complete or partial remission may receive a second course of treatment as above.
Patients age 50 and over with "core binding factor" acute myeloid leukemia (AML) (e.g., t[8;21], inv[16], or t[16;16]) achieving a complete remission after course 1 of treatment may receive 3-4 courses of consolidation therapy comprising high-dose cytarabine at the discretion of the investigator.
After completion of study treatment, patients are followed periodically.
- Conditions
- Adult Acute Basophilic Leukemia, Adult Acute Eosinophilic Leukemia, Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monoblastic Leukemia (M5a), Adult Acute Monocytic Leukemia (M5b)
- Being tested
- alvocidib, cytarabine, mitoxantrone hydrochloride
- 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.
alvocidibDrug
Also called FLAVO, flavopiridol, HMR 1275, L-868275
Given IV
cytarabineDrug
Also called ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U
Given IV
mitoxantrone hydrochlorideDrug
Also called CL 232315, DHAD, DHAQ, Novantrone
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (alvocidib, cytarabine, mitoxantrone hydrochloride) | Experimental | Patients receive alvocidib IV over 1 hour on days 1-3, cytarabine IV continuously over 72 hours on days 6-8, and mitoxantrone hydrochloride IV over 1-2 hours on day 9. Beginning 35-63 days after completion of course 1, patients achieving complete or partial remission may receive a second course of treatment as above.
Patients age 50 and over with "core binding factor" acute myeloid leukemia (AML) (e.g., t[8;21], inv[16], or t[16;16]) achieving a complete remission after course 1 of treatment may receive 3-4 courses of consolidation therapy comprising high-dose cytarabine at the discretion of the investigator. Receives: Drug: alvocidib; Drug: cytarabine; Drug: mitoxantrone hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete Response
Bone marrow showing less than 5% myeloblasts with normal maturation of all cell lines, an Absolute Neutrophil Count of at least 1000/mililiter and a platelet count of 100,000 mililiter, absence of blast in peripheral blood, absence of identifiable leukemic cells in the bone marrow, clearance of disease-associated cytogenetic abnormalities, and clearance of any previously existing extramedullary disease. A complete remission must be confirmed 4 to 6 weeks after the initial documentation. If possible, at least one bone marrow biopsy should be performed to confirm the complete remission.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2006 (estimated)
- Study startOct 2006
- Primary completionJul 2008
- Study completionNov 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Judith Karp, Principal investigator, Johns Hopkins University/Sidney Kimmel Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00407966
- Sponsor's protocol ID
- NCI-2012-02986
- Other IDs
- NCI-2012-02986, U01CA070095, P30CA006973, J0669, 7845
- Status last verified
- Dec 2012
- First submitted
- 4 Dec 2006
- Last updated
- 4 Aug 2015
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Karp JE, Garrett-Mayer E, Estey EH, Rudek MA, Smith BD, Greer JM, Drye DM, Mackey K, Dorcy KS, Gore SD, Levis MJ, McDevitt MA, Carraway HE, Pratz KW, Gladstone DE, Showel MM, Othus M, Doyle LA, Wright JJ, Pagel JM. Randomized phase II study of two schedules of flavopiridol given as timed sequential therapy with cytosine arabinoside and mitoxantrone for adults with newly diagnosed, poor-risk acute myelogenous leukemia. Haematologica. 2012 Nov;97(11):1736-42. doi: 10.3324/haematol.2012.062539. Epub 2012 Jun 24.
PubMed 22733022
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Alvocidib (NSC 649890, Flavopiridol) in Timed Sequential Combination With Cytosine Arabinoside (Ara-C) and Mitoxantrone for Adults With Newly Diagnosed, Previously Untreated, Poor-Risk Acute Myelogenous Leukemias
- ClinicalTrials.gov ID
- NCT00407966
- Acronym / sponsor ID
- NCI-2012-02986
- Conditions
- Adult Acute Basophilic Leukemia, Adult Acute Eosinophilic Leukemia, Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monoblastic Leukemia (M5a), Adult Acute Monocytic Leukemia (M5b)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Oct 2006
- Primary completion
- Jul 2008 (actual)
- Study completion
- Nov 2009 (actual)
- First posted
- 5 Dec 2006 (estimated)
- Results
- Posted 11 Feb 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial is studying the side effects and how well giving alvocidib together with cytarabine and mitoxantrone works in treating patients with newly diagnosed acute myeloid leukemia. Drugs used in chemotherapy, such as alvocidib, cytarabine, and mitoxantrone, 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.
Detailed description
PRIMARY OBJECTIVES:
- To determine the efficacy and toxicities of flavopiridol (alvocidib) followed by ara-C and mitoxantrone in adults with newly diagnosed acute myelogenous leukemia (AML) with poor-risk features.
II. To determine the disease free and overall survival of patients exhibiting a response to treatment with flavopiridol followed by ara-C and mitoxantrone.
OUTLINE:
Patients receive alvocidib IV over 1 hour on days 1-3, cytarabine IV continuously over 72 hours on days 6-8, and mitoxantrone hydrochloride IV over 1-2 hours on day 9. Beginning 35-63 days after completion of course 1, patients achieving complete or partial remission may receive a second course of treatment as above.
Patients age 50 and over with "core binding factor" acute myeloid leukemia (AML) (e.g., t[8;21], inv[16], or t[16;16]) achieving a complete remission after course 1 of treatment may receive 3-4 courses of consolidation therapy comprising high-dose cytarabine at the discretion of the investigator.
After completion of study treatment, patients are followed periodically.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (alvocidib, cytarabine, mitoxantrone hydrochloride) | Experimental | Drug: alvocidib, Drug: cytarabine, Drug: mitoxantrone hydrochloridePatients receive alvocidib IV over 1 hour on days 1-3, cytarabine IV continuously over 72 hours on days 6-8, and mitoxantrone hydrochloride IV over 1-2 hours on day 9. Beginning 35-63 days after completion of course 1, patients achieving complete or partial remission may receive a second course of treatment as above. Patients age 50 and over with "core binding factor" acute myeloid leukemia (AML) (e.g., t[8;21], inv[16], or t[16;16]) achieving a complete remission after course 1 of treatment may receive 3-4 courses of consolidation therapy comprising high-dose cytarabine at the discretion of the investigator. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Adults with established, pathologically confirmed diagnoses of newly diagnosed, poor-risk Acute Myeloid Leukemia(AML) including de novo and secondary Acute Myeloid Leukemias but excluding newly diagnosed acute progranulocytic leukemia (APL, M3) will be considered eligible for study
- ECOG performance status 0-2
- Patient must be able to give informed consent
- Serum creatinine =< 2.0
- ALT, AST =< 5 x upper limit of normal
Key exclusion criteria (10 listed)
- Patients who have received hydroxyurea alone or have received non-cytotoxic therapies previously for MDS or MPD (e.g., thalidomide or lenalidomide, interferon, cytokines, low-dose 5-azacytidine, low-dose cytoxan) will be eligible for this trial
- Any previous treatment with flavopiridol
- Concomitant chemotherapy, radiation therapy, or immunotherapy
- Hyperleukocytosis with >= 50,000 blasts/uL; leukapheresis or hydroxyurea may be used immediately prior to study drug administration for cytoreduction; must be stopped 24 hours before first dose of Flavopiridol
- Acute Progranulocytic Leukemia (APL, M3)
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 |
|---|---|---|
| alvocidibAlso: FLAVO, flavopiridol, HMR 1275, L-868275Given IV | Drug | Treatment (alvocidib, cytarabine, mitoxantrone hydrochloride) |
| cytarabineAlso: ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-UGiven IV | Drug | Treatment (alvocidib, cytarabine, mitoxantrone hydrochloride) |
| mitoxantrone hydrochlorideAlso: CL 232315, DHAD, DHAQ, NovantroneGiven IV | Drug | Treatment (alvocidib, cytarabine, mitoxantrone hydrochloride) |
Primary outcome
Complete Response
Time frame: 6 months
Bone marrow showing less than 5% myeloblasts with normal maturation of all cell lines, an Absolute Neutrophil Count of at least 1000/mililiter and a platelet count of 100,000 mililiter, absence of blast in peripheral blood, absence of identifiable leukemic cells in the bone marrow, clearance of disease-associated cytogenetic abnormalities, and clearance of any previously existing extramedullary disease. A complete remission must be confirmed 4 to 6 weeks after the initial documentation. If possible, at least one bone marrow biopsy should be performed to confirm the complete remission.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 22733022Karp JE, Garrett-Mayer E, Estey EH, Rudek MA, Smith BD, Greer JM, Drye DM, Mackey K, Dorcy KS, Gore SD, Levis MJ, McDevitt MA, Carraway HE, Pratz KW, Gladstone DE, Showel MM, Othus M, Doyle LA, Wright JJ, Pagel JM. Randomized phase II study of two schedules of flavopiridol given as timed sequential therapy with cytosine arabinoside and mitoxantrone for adults with newly diagnosed, poor-risk acute myelogenous leukemia. Haematologica. 2012 Nov;97(11):1736-42. doi: 10.3324/haematol.2012.062539. Epub 2012 Jun 24.
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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.
Judith Karp principal investigator
Johns Hopkins University/Sidney Kimmel 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 2 study testing alvocidib, cytarabine and mitoxantrone hydrochloride 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 13 inclusion and 10 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 4 Aug 2015. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Feb 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Complete Response (time frame: 6 months). 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 NCT00407966, which also lists 1 linked publication.
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 4 Aug 2015.