Adult Acute Basophilic LeukemiaPhase 1NCT00101231
Flavopiridol in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Chronic Myelogenous Leukemia
A Phase 1 study testing alvocidib 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 flavopiridol 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 1 year 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
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 88 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2004to Nov 2012
- 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 1 year and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Histologically confirmed diagnosis of one of the following:
- Acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) meeting 1 of the following criteria:
- Refractory to initial treatment (stratum 1)
- Recurrent disease after prior high-dose chemotherapy with or without stem cell support (stratum 1)
- High-risk refractory disease defined as failed ≥ 2 regimens for remission induction (i.e., twice induction failure) (stratum 2)
- High-risk relaspsed disease defined as disease in second or greater bone marrow relapse (stratum 2)
Show all 51Show fewer
- Chronic myelogenous leukemia in blast crisis (stratum 1)
- Myeloid or lymphoid blast crisis that did not respond to or progressed after prior high-dose imatinib mesylate (600-800 mg/day for ≥ 2 weeks)
- No acute promyelocytic leukemia
- Ineligible for or unwilling to undergo potentially curative allogeneic or autologous stem cell transplantation
- Patients with relapsed AML that is refractory to re-induction therapy comprising an active, intensive salvage regimen are eligible
- CNS involvement allowed provided there are no residual leukemic cells in the cerebrospinal fluid after intrathecal chemotherapy or radiotherapy
- Performance status - ECOG ≥ 2 for patients > 10 years of age
- Performance status - Lansky 50-100% for patients ≤ 10 years of age
- At least 8 weeks
- Bilirubin ≤ 2 times upper limit of normal (ULN)* (unless due to Gilbert's syndrome)
- ALT and AST ≤ 5 times ULN*
- Creatinine ≤ 2.0 mg/dL* (stratum 1)
- Creatinine > 1.3 times ULN (stratum 2)
- LVEF ≥ 40% by echocardiogram or MUGA (stratum 1)
- Shortening fraction ≥ 28% by echocardiogram (stratum 2)
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- HIV negative
- No history of allergy to study drug
- No active infection requiring IV antibiotics
- No serious medical or psychiatric illness that would preclude giving informed consent or limit survival
- No other uncontrolled illness
- See Disease Characteristics
- Recovered from all prior immunotherapy treatment-related toxicity (stratum 2)
- More than 8 weeks since prior biological agents (e.g., monoclonal antibodies) (stratum 2)
- See Disease Characteristics
- Recovered from all prior chemotherapy treatment-related toxicity (stratum 2)
- More than 24 hours since prior hydroxyurea (for patients who do not have highly proliferative disease)*
- More than 2 weeks since other prior chemotherapy (6 weeks for nitrosourea or mitomycin)
- No other concurrent chemotherapy
- Prior hydrea and/or steroids allowed (stratum 2)
- No concurrent hormones, except steroids for adrenal failure or infusional toxicity (i.e., cytokine release syndrome) or hormones for non-disease-related conditions (e.g., insulin for diabetes)
- See Disease Characteristics
- Recovered from all prior radiotherapy treatment-related toxicity (stratum 2)
- More than 2 weeks since prior radiotherapy
- No concurrent palliative radiotherapy
- Post stem cell transplant allowed provided completion ≥ 4 months prior to study entry and no evidence of active acute or chronic graft vs host disease (stratum 2)
- No other concurrent investigational agents
- No concurrent chronic systemic anticoagulant therapy for a medical condition (e.g., deep vein thrombosis or atrial fibrillation)
- Concurrent heparin allowed to maintain central line patency (i.e., catheter flush)
- No other concurrent anticancer therapy
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Ohio State University Medical Center
Columbus, Ohio, 43210
About this study
Official title: A Dose Escalation Study of Flavopiridol (NSC 649890) Administered as a 30 Minute Loading Dose Followed by a 4-Hour Infusion in Patients With Relapsed and Refractory Acute Leukemias
This phase I trial is studying the side effects and best dose of flavopiridol in treating patients with relapsed or refractory acute myeloid leukemia, acute lymphoblastic leukemia, or chronic myelogenous leukemia. Drugs used in chemotherapy, such as flavopiridol, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the maximal tolerable dose of flavopiridol in relapsed or refractory acute leukemia in adults (Stratum 1) and children (Stratum 2).
II. To define the qualitative and quantitative toxicities of flavopiridol in regard to organ specificity, time course, predictability, and reversibility.
III. To determine the preliminary clinical activity of flavopiridol in adults (Stratum 1) and children (Stratum 2) using this novel schedule in acute leukemia.
IV. To evaluate the plasma and cellular pharmacokinetics of flavopiridol in patients enrolled on this study.
SECONDARY OBJECTIVES:
- To measure pharmacodynamic measurements including effects on cell cycle; down modulation of bcl-2, mcl-1, XIAP, bax, RNA polymerase II phosphorylation; and signaling via the VEGF (VEGF, VEGF-R1, VEGF-R2, HIF-1), NF-Kappa B pathway, and PI3kinase pathway; and correlate with Css and other pharmacokinetic features.
II. To assess drug induced apoptosis of acute leukemia cells in vitro and subsequent relationship to clinical response based upon Css of flavopiridol attained in vivo.
II. To determine if increase in inflammatory cytokines (TNF-alpha, gamma-IFN, IL-6 and IL-8) correlate with pharmacokinetics, pharmacodynamics, laboratory (decrease in serum albumin) and clinical (hypotension observed with the first administration of flavopiridol) parameters of treatment.
OUTLINE: This is a dose-escalation study. Patients are stratified according to age group (adult [≥ 18 years] vs pediatric [1-17 years]).
Patients receive flavopiridol intravenously (IV) over 30 minutes followed by a 4-hour infusion on days 1-3. Treatment repeats every 21 days for up to 6 courses in the absence of unacceptable toxicity or disease progression. Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Patients are followed up every 2 months for 1 year and then every 6 months for 4 years.
- 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
- 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
| Study group | Role | What they receive |
|---|---|---|
| Treatment (flavopiridol) | Experimental | Patients receive flavopiridol IV over 30 minutes followed by a 4-hour infusion on days 1-3. Treatment repeats every 21 days for up to 6 courses in the absence of unacceptable toxicity or disease progression. Receives: Drug: alvocidib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximal tolerable dose of flavopiridol
Measured: Day 21
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2005 (estimated)
- Study startOct 2004
- Primary completionNov 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 88 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- William Blum, Principal investigator, Ohio State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00101231
- Sponsor's protocol ID
- NCI-2012-01461
- Other IDs
- OSU 0479, NCI-6947, OSU-2004C0085, OSU-0479, CDR0000404374, U01CA076576
- Status last verified
- Jun 2013
- First submitted
- 7 Jan 2005
- Last updated
- 4 Jun 2013
- Results posted
- No
Publications
Blum W, Phelps MA, Klisovic RB, Rozewski DM, Ni W, Albanese KA, Rovin B, Kefauver C, Devine SM, Lucas DM, Johnson A, Schaaf LJ, Byrd JC, Marcucci G, Grever MR. Phase I clinical and pharmacokinetic study of a novel schedule of flavopiridol in relapsed or refractory acute leukemias. Haematologica. 2010 Jul;95(7):1098-105. doi: 10.3324/haematol.2009.017103. Epub 2010 May 11.
PubMed 20460644
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Dose Escalation Study of Flavopiridol (NSC 649890) Administered as a 30 Minute Loading Dose Followed by a 4-Hour Infusion in Patients With Relapsed and Refractory Acute Leukemias
- ClinicalTrials.gov ID
- NCT00101231
- Acronym / sponsor ID
- NCI-2012-01461
- 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 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 88 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Oct 2004
- Primary completion
- Nov 2012 (actual)
- First posted
- 10 Jan 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 flavopiridol in treating patients with relapsed or refractory acute myeloid leukemia, acute lymphoblastic leukemia, or chronic myelogenous leukemia. Drugs used in chemotherapy, such as flavopiridol, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.
Detailed description
PRIMARY OBJECTIVES:
- To determine the maximal tolerable dose of flavopiridol in relapsed or refractory acute leukemia in adults (Stratum 1) and children (Stratum 2).
II. To define the qualitative and quantitative toxicities of flavopiridol in regard to organ specificity, time course, predictability, and reversibility.
III. To determine the preliminary clinical activity of flavopiridol in adults (Stratum 1) and children (Stratum 2) using this novel schedule in acute leukemia.
IV. To evaluate the plasma and cellular pharmacokinetics of flavopiridol in patients enrolled on this study.
SECONDARY OBJECTIVES:
- To measure pharmacodynamic measurements including effects on cell cycle; down modulation of bcl-2, mcl-1, XIAP, bax, RNA polymerase II phosphorylation; and signaling via the VEGF (VEGF, VEGF-R1, VEGF-R2, HIF-1), NF-Kappa B pathway, and PI3kinase pathway; and correlate with Css and other pharmacokinetic features.
II. To assess drug induced apoptosis of acute leukemia cells in vitro and subsequent relationship to clinical response based upon Css of flavopiridol attained in vivo.
II. To determine if increase in inflammatory cytokines (TNF-alpha, gamma-IFN, IL-6 and IL-8) correlate with pharmacokinetics, pharmacodynamics, laboratory (decrease in serum albumin) and clinical (hypotension observed with the first administration of flavopiridol) parameters of treatment.
OUTLINE: This is a dose-escalation study. Patients are stratified according to age group (adult [≥ 18 years] vs pediatric [1-17 years]).
Patients receive flavopiridol intravenously (IV) over 30 minutes followed by a 4-hour infusion on days 1-3. Treatment repeats every 21 days for up to 6 courses in the absence of unacceptable toxicity or disease progression. Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Patients are followed up every 2 months for 1 year and then every 6 months for 4 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (flavopiridol) | Experimental | Drug: alvocidibPatients receive flavopiridol IV over 30 minutes followed by a 4-hour infusion on days 1-3. Treatment repeats every 21 days for up to 6 courses in the absence of unacceptable toxicity or disease progression. |
Who may qualify
- Ages
- 1 year and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (51 listed)
- Histologically confirmed diagnosis of one of the following:
- No acute promyelocytic leukemia
- Ineligible for or unwilling to undergo potentially curative allogeneic or autologous stem cell transplantation
- CNS involvement allowed provided there are no residual leukemic cells in the cerebrospinal fluid after intrathecal chemotherapy or radiotherapy
- Performance status - ECOG ≥ 2 for patients > 10 years of age
Key exclusion criteria (0 listed)
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 (flavopiridol) |
Primary outcome
Maximal tolerable dose of flavopiridol
Time frame: Day 21
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2013.
- Derived from this study: PubMed 20460644Blum W, Phelps MA, Klisovic RB, Rozewski DM, Ni W, Albanese KA, Rovin B, Kefauver C, Devine SM, Lucas DM, Johnson A, Schaaf LJ, Byrd JC, Marcucci G, Grever MR. Phase I clinical and pharmacokinetic study of a novel schedule of flavopiridol in relapsed or refractory acute leukemias. Haematologica. 2010 Jul;95(7):1098-105. doi: 10.3324/haematol.2009.017103. Epub 2010 May 11.
Related trials for Adult Acute Basophilic Leukemia
Active, not recruitingPhase 2
Decitabine, Cytarabine, and Daunorubicin Hydrochloride in Treating Patients With Acute Myeloid Leukemia
Acute Myeloid Leukemia, Adult Acute Basophilic Leukemia
Active, not recruitingObservational study
Multidrug Resistance Genes in Patients With Acute Myeloid Leukemia
Leukemia
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.
William Blum principal investigator
Ohio State 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 alvocidib 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 51 inclusion and 0 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: stopped early, as of the sponsor's last update on 4 Jun 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 was stopped early. Results are not available in the source record.
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?
Maximal tolerable dose of flavopiridol (time frame: Day 21). 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 NCT00101231, 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 Jun 2013.