Acute Myeloid LeukemiaPhase 1NCT00081822
Study of Clofarabine & Cytosine Arabinoside Therapy for Older Adults With Acute Myeloid Leukemia
A Phase 1 study testing clofarabine and Ara-C in people with Acute Myeloid Leukemia, run by University of Alabama at Birmingham at 3 sites in United States.
Trial summary
The purpose of this study is to determine the recommended phase II dose of clofarabine when administered in combination with standard dose Ara-C to older (>=60 years of age) patients with newly diagnosed acute myeloid leukemia (AML). Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- clofarabine and Ara-C
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 3 sitesUnited States
- Study dates
- Jan 2004to Aug 2011
- 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 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Have newly diagnosed AML (FAB classification types M0-M2 or M4-M7 or WHO classification) excluding acute promyelocytic leukemia (APL) or AML with any of the following chromosomal translocations: t(15;17)(q22;q21); t(11;17)(q23;q21); t(11;17)(q13;q21); t(5;17)(q32;q12)..
- Have greater than or equal to 20% blasts in the bone marrow.
- Have greater than or equal to 20% cellularity in the bone marrow.
- Provide written informed consent.
- Must be 60-75 years of age at diagnosis.
- Have an Karnofsky performance status of ≥60.
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- Women of childbearing potential (<1 year post-menopausal unless surgically sterilized) and sexually active males must have a negative urine pregnancy test, and agree to use an effective barrier method of birth control (i.e. latex condom, diaphragm, cervical cap, etc) to avoid pregnancy.
- Able to comply with study procedures and follow-up examinations.
- Have adequate organ function as indicated by the following laboratory values, obtained within 7 days prior to registration:
- Parameter Required Value (IS units) Renal Serum creatinine <1.1 mg/dL Hepatic Serum bilirubin <2 x ULN AST and ALT ≤5 x ULN ULN = Institutional Upper Limit of Normal. Inclusion Laboratory Values
Who cannot join
- Patients with pre-existing myelodysplastic syndrome, or with antecedent hematologic disorder of >3 months duration, will be excluded. Those with concomitant myelodysplasia/trilineage dysplasia noted at the time of diagnosis of AML will be eligible 74
- Have secondary AML (AML following chemotherapy or radiation therapy).
- Have an active, uncontrolled systemic infection considered opportunistic, life threatening, or clinically significant at the time of treatment.
- Have a psychiatric disorder(s) that would interfere with consent, study participation or follow-up.
- Are receiving other chemotherapy or corticosteroids (unless the latter is administered at a low dose for pre-medication purposes or for the treatment of chronic conditions - e.g., rheumatoid arthritis).
- Have received prior treatment for leukemia. Patients who have received growth factors, cytokine support, leukapheresis, hydroxyurea, or cranial irradiation will be allowed but must discontinue treatment at least 24 hours prior to beginning treatment with clofarabine. If used, hydroxyurea must be discontinued 48 hours prior to the initiation of chemotherapy.
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- Have any other severe concurrent disease (severe coronary artery disease (NYHA class >II), significant neurological disorder, uncontrolled diabetes, etc.), which, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
- Have active central nervous system involvement with leukemia.
- Other malignancy within the past year, with the exception of basal cell or non-metastatic squamous cell carcinoma of the skin
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of Alabama at Birmingham
Birmingham, Alabama, 35233
The Cleveland Clinic Foundation
Cleveland, Ohio, 44195
The University of Nebraska
Omaha, Nebraska, 68198
About this study
Official title: A Phase I Study of Clofarabine & Cytosine Arabinoside Therapy for Older Adults With Acute Myeloid Leukemia
The purpose of this study is to determine the recommended phase II dose of clofarabine when administered in combination with standard dose Ara-C to older (>=60 years of age) patients with newly diagnosed acute myeloid leukemia (AML).
Read the detailed description
This phase I/II trial will include an initial dose escalation of clofarabine with a fixed standard dose of Ara-C in phase I to determine the 'optimal phase II dose'. Patients will be enrolled into phase I in cohorts of 3-6 beginning at Dose Level I of clofarabine (30 mg/m2/day, days 2-6). If 0/3 or 1/6 patients experience dose-limiting toxicity (DLT), clofarabine will be escalated to Dose Level II (40mg/m2/day, days 2-6). If >1/3 or ≥2/6 patients experience DLT on Dose Level II, then Dose Level I will be declared the optimal phase II dose. However, if 0/3 or 1/6 patients experience DLT on Dose Level II, then Dose Level II will be declared the optimal phase II dose. In the event that ≥2 patients experience DLT at Dose Level I, clofarabine will be dose reduced to Dose Level -I (22.5mg/m2/day, days 2-6). Accrual will continue in cohorts of 3-6 patients, in a phase I fashion. If 0/3 or 1/6 patients experience DLT, then Dose Level -I will be declared the 'optimal phase II dose'. In the event that ≥2 patients experience DLT at Dose Level -I, clofarabine will be further dose reduced to Dose Level -II (15mg/m2/day, days 2-6). Accrual will again proceed in cohorts of 3-6 patients. If 0/3 or 1/6 experience DLT, then Dose Level -II will be declared the 'optimal phase II dose'. In the event that ≥2 patients experience DLT at Dose Level -II, accrual to the protocol will be halted.
Enrollment will proceed at the optimal phase II dose in a Simon 2-stage design to determine the CR rate and treatment-related mortality initially in 16 patients; if the CR rate and TRM is acceptable , then enrollment will continue to approximately 46 patients or until complete.
Induction Therapy (cycle 1)
- 7 day cycle Day 1 Aggressive Hydration x12-24hrs, followed by Ara-C 100mg/m2/day by 24hr IV continuous infusion days 1-7
- PK analysis Ara-C alone on Day 1 (plasma \& intracellular) Day 2 Dexamethasone 10mg IV QD prior to clofarabine days 2-6 Clofarabine 2 hour daily infusion days 2-6
- PK analysis of Ara-C \& clofarabine on Day 2
- Bone Marrow Apoptosis analysis (plasma \& intracellular) Day 3 *Bone Marrow Apoptosis analysis (plasma \& intracellular) Day 6 *PK analysis of Ara-C and clofarabine (plasma only) (UAB only) Day 8 Initiation of prophylactic antibiotic, antifungal \& antiviral therapy Day 15 *QOL analysis Day 15-22 Restaging BM Re-Induction if appropriate (see below) Day 16 GM-CSF 250μg/m2 daily until ANC >1,500/μl (if D15 BM aplasia, no residual AML) Day 28-49 Outcome BM, assessment of response Re-Induction (PR) or Post-Remission therapy (CR)
- QOL analysis 2 weeks after hospital discharge (approximately Day 42)
Re-Induction (cycle 2 if appropriate) (if Partial Remission after Induction, day 15-49) *5 day cycle Aggressive Hydration x12-24hrs Day 1 Dexamethasone 10mg IV QD days 1-5 Day 1 Clofarabine 2 hour daily infusion days 1-5 Day 1 Ara-C 100mg/m2/day days 1-5 (begin 4 hours after end of clofarabine infusion) Day 7 GM-CSF 250μg/m2 daily may be used until recovery ANC >1,500/μl Day 7 Initiation of prophylactic antibiotic, antifungal \& antiviral therapy
Post-Remission Therapy (cycles 2 \& 3 if appropriate) (if Complete Remission after Induction; must have ANC>1,000/μl , platelets >100/μl)
*5 day cycle Aggressive Hydration x12-24hrs Day 1 Dexamethasone 10mg IV QD days 1-5 Day 1 Clofarabine 2 hour daily infusion days 1-5 Day 1 Ara-C 100mg/m2/day days 1-5 (begin 4 hours after end of clofarabine infusion) Day 7 GM-CSF 250μg/m2 daily may be used until recovery ANC >1,500/μl Day 7 Initiation of prophylactic antibiotic, antifungal \& antiviral therapy
Follow-up Monthly x 12 months 3-monthly x 2 years 4-monthly x 1 year 6-monthly x 1 year Annually thereafter
- Conditions
- Acute Myeloid Leukemia
- Being tested
- clofarabine, Ara-C
- Keywords
- Foran, clofarabine, cytosine arabinoside, acute myeloid leukemia
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
clofarabineDrug
Also called CLOFAREX TM
Clofarabine should be administered by daily intravenous infusion over 2 hours.Following demonstration of DLT at Dose Level -I (22.5 mg/m2/day days 2-6) and demonstration that Dose Level -II (15mg/m2day days 2-6) is the 'optimal phase II dose', an additional Dose Level -1½ (20mg/m2/day, days 2-6) will be added to explore an increased dose of clofarabine intermediate between Dose Levels -I and -II.
Ara-CDrug
Also called Cytosine arabinoside, Cytarabine, Cytosar-U, Arabinosyl
Ara-C: Administer Ara-C by continuous infusion of 100mg/m2/day on days 1 to 7 for cycle 1, and on days 1 to 5 for cycles 2 \& 3.
| Study group | Role | What they receive |
|---|---|---|
| Clofarabine + Ara-C | Other | An initial dose escalation of clofarabine with a fixed standard dose of Ara-C in phase I will be used to determine an optimal phase II dose. Receives: Drug: clofarabine; Drug: Ara-C |
What is being measured
The primary outcome is the main question the study is designed to answer.
Median time to complete response (CR)
Measured: 1 year
Secondary outcomes (1)
To evaluate quality of life parameters before, during and after therapy in the older adult (>60 years) population
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2004 (estimated)
- Study startJan 2004
- Primary completionApr 2009
- Study completionAug 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe 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
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- Genzyme, a Sanofi Company
- Responsible party
- Sponsor
- Investigators
- James M Foran, MD, Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00081822
- Sponsor's protocol ID
- F040114019
- Other IDs
- UAB 0341
- Status last verified
- Apr 2012
- First submitted
- 21 Apr 2004
- Last updated
- 20 Apr 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Clofarabine & Cytosine Arabinoside Therapy for Older Adults With Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT00081822
- Acronym / sponsor ID
- F040114019
- Conditions
- Acute Myeloid Leukemia
- Keywords
- Foran, clofarabine, cytosine arabinoside, acute myeloid leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Collaborators
- Genzyme, a Sanofi Company
- Study start
- Jan 2004
- Primary completion
- Apr 2009 (actual)
- Study completion
- Aug 2011 (actual)
- First posted
- 23 Apr 2004 (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.
The purpose of this study is to determine the recommended phase II dose of clofarabine when administered in combination with standard dose Ara-C to older (>=60 years of age) patients with newly diagnosed acute myeloid leukemia (AML).
Detailed description
This phase I/II trial will include an initial dose escalation of clofarabine with a fixed standard dose of Ara-C in phase I to determine the 'optimal phase II dose'. Patients will be enrolled into phase I in cohorts of 3-6 beginning at Dose Level I of clofarabine (30 mg/m2/day, days 2-6). If 0/3 or 1/6 patients experience dose-limiting toxicity (DLT), clofarabine will be escalated to Dose Level II (40mg/m2/day, days 2-6). If >1/3 or ≥2/6 patients experience DLT on Dose Level II, then Dose Level I will be declared the optimal phase II dose. However, if 0/3 or 1/6 patients experience DLT on Dose Level II, then Dose Level II will be declared the optimal phase II dose. In the event that ≥2 patients experience DLT at Dose Level I, clofarabine will be dose reduced to Dose Level -I (22.5mg/m2/day, days 2-6). Accrual will continue in cohorts of 3-6 patients, in a phase I fashion. If 0/3 or 1/6 patients experience DLT, then Dose Level -I will be declared the 'optimal phase II dose'. In the event that ≥2 patients experience DLT at Dose Level -I, clofarabine will be further dose reduced to Dose Level -II (15mg/m2/day, days 2-6). Accrual will again proceed in cohorts of 3-6 patients. If 0/3 or 1/6 experience DLT, then Dose Level -II will be declared the 'optimal phase II dose'. In the event that ≥2 patients experience DLT at Dose Level -II, accrual to the protocol will be halted.
Enrollment will proceed at the optimal phase II dose in a Simon 2-stage design to determine the CR rate and treatment-related mortality initially in 16 patients; if the CR rate and TRM is acceptable , then enrollment will continue to approximately 46 patients or until complete.
Induction Therapy (cycle 1)
- 7 day cycle Day 1 Aggressive Hydration x12-24hrs, followed by Ara-C 100mg/m2/day by 24hr IV continuous infusion days 1-7
- PK analysis Ara-C alone on Day 1 (plasma \& intracellular) Day 2 Dexamethasone 10mg IV QD prior to clofarabine days 2-6 Clofarabine 2 hour daily infusion days 2-6
- PK analysis of Ara-C \& clofarabine on Day 2
- Bone Marrow Apoptosis analysis (plasma \& intracellular) Day 3 *Bone Marrow Apoptosis analysis (plasma \& intracellular) Day 6 *PK analysis of Ara-C and clofarabine (plasma only) (UAB only) Day 8 Initiation of prophylactic antibiotic, antifungal \& antiviral therapy Day 15 *QOL analysis Day 15-22 Restaging BM Re-Induction if appropriate (see below) Day 16 GM-CSF 250μg/m2 daily until ANC >1,500/μl (if D15 BM aplasia, no residual AML) Day 28-49 Outcome BM, assessment of response Re-Induction (PR) or Post-Remission therapy (CR)
- QOL analysis 2 weeks after hospital discharge (approximately Day 42)
Re-Induction (cycle 2 if appropriate) (if Partial Remission after Induction, day 15-49) *5 day cycle Aggressive Hydration x12-24hrs Day 1 Dexamethasone 10mg IV QD days 1-5 Day 1 Clofarabine 2 hour daily infusion days 1-5 Day 1 Ara-C 100mg/m2/day days 1-5 (begin 4 hours after end of clofarabine infusion) Day 7 GM-CSF 250μg/m2 daily may be used until recovery ANC >1,500/μl Day 7 Initiation of prophylactic antibiotic, antifungal \& antiviral therapy
Post-Remission Therapy (cycles 2 \& 3 if appropriate) (if Complete Remission after Induction; must have ANC>1,000/μl , platelets >100/μl)
*5 day cycle Aggressive Hydration x12-24hrs Day 1 Dexamethasone 10mg IV QD days 1-5 Day 1 Clofarabine 2 hour daily infusion days 1-5 Day 1 Ara-C 100mg/m2/day days 1-5 (begin 4 hours after end of clofarabine infusion) Day 7 GM-CSF 250μg/m2 daily may be used until recovery ANC >1,500/μl Day 7 Initiation of prophylactic antibiotic, antifungal \& antiviral therapy
Follow-up Monthly x 12 months 3-monthly x 2 years 4-monthly x 1 year 6-monthly x 1 year Annually thereafter
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Clofarabine + Ara-C | Other | Drug: clofarabine, Drug: Ara-CAn initial dose escalation of clofarabine with a fixed standard dose of Ara-C in phase I will be used to determine an optimal phase II dose. |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Have newly diagnosed AML (FAB classification types M0-M2 or M4-M7 or WHO classification) excluding acute promyelocytic leukemia (APL) or AML with any of the following chromosomal translocations: t(15;17)(q22;q21); t(11;17)(q23;q21); t(11;17)(q13;q21); t(5;17)(q32;q12)..
- Have greater than or equal to 20% blasts in the bone marrow.
- Have greater than or equal to 20% cellularity in the bone marrow.
- Provide written informed consent.
- Must be 60-75 years of age at diagnosis.
Key exclusion criteria (9 listed)
- Patients with pre-existing myelodysplastic syndrome, or with antecedent hematologic disorder of >3 months duration, will be excluded. Those with concomitant myelodysplasia/trilineage dysplasia noted at the time of diagnosis of AML will be eligible 74
- Have secondary AML (AML following chemotherapy or radiation therapy).
- Have an active, uncontrolled systemic infection considered opportunistic, life threatening, or clinically significant at the time of treatment.
- Have a psychiatric disorder(s) that would interfere with consent, study participation or follow-up.
- Are receiving other chemotherapy or corticosteroids (unless the latter is administered at a low dose for pre-medication purposes or for the treatment of chronic conditions - e.g., rheumatoid arthritis).
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 |
|---|---|---|
| clofarabineAlso: CLOFAREX TMClofarabine should be administered by daily intravenous infusion over 2 hours.Following demonstration of DLT at Dose Level -I (22.5 mg/m2/day days 2-6) and demonstration that Dose Level -II (15mg/m2day days 2-6) is the 'optimal phase II dose', an additional Dose Level -1½ (20mg/m2/day, days 2-6) will be added to explore an increased dose of clofarabine intermediate between Dose Levels -I and -II. | Drug | Clofarabine + Ara-C |
| Ara-CAlso: Cytosine arabinoside, Cytarabine, Cytosar-U, ArabinosylAra-C: Administer Ara-C by continuous infusion of 100mg/m2/day on days 1 to 7 for cycle 1, and on days 1 to 5 for cycles 2 \& 3. | Drug | Clofarabine + Ara-C |
Primary outcome
Median time to complete response (CR)
Time frame: 1 year
1 secondary outcome
To evaluate quality of life parameters before, during and after therapy in the older adult (>60 years) population
Time frame: 1 year
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 20 Apr 2012.
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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.
James M Foran, MD principal investigator
University of Alabama at Birmingham
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing clofarabine and Ara-C in people with Acute Myeloid Leukemia, run by University of Alabama at Birmingham at 3 sites 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 10 inclusion and 9 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 20 Apr 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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?
Median time to complete response (CR) (time frame: 1 year). 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 20 Apr 2012.