Leukemia, MyeloidPhase 2NCT00065143
Clofarabine Plus Cytarabine in Patients With Previously Untreated Acute Myeloid Leukemia and High-risk Myelodysplastic Syndrome
A Phase 2 study testing clofarabine and Ara-C in people with Leukemia, Myeloid and Myelodysplastic Syndromes, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
The goal of this clinical research study is to learn if clofarabine, when given in combination with ara-C (cytarabine), can help to improve the disease's response to therapy and to increase the duration of response in patients who are 50 years or older with leukemia. Read more about this study
- Who is it for?
- Ages 50 to 74 years
- Conditions the study is for
- Leukemia, Myeloid, Myelodysplastic Syndromes
- What is being tested?
- clofarabine and Ara-C
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Jun 2003to 22 Feb 2006
- Phase
- Phase 2
- 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 50 to 74 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Previously untreated acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) (> 10% blasts). Prior therapy with hydroxyurea, single agent chemotherapy (e.g. decitabine), hematopoietic growth factors, biological or "targeted" therapies are allowed.
- Age > 50 years to < 74 years (diploid cytogenetics) and < 69 years (abnormal cytogenetics).
- ECOG performance status </= 2.
- Sign a written informed consent form.
- Adequate liver function (total bilirubin < 2mg/dL, SGPT or SGOT < x 4 ULN) and renal function (serum creatinine < 2mg/dL).
- Male and female patients who are fertile agree to use an effective barrier method of birth control (ie, latex condom, diaphragm, cervical cap, etc) to avoid pregnancy. Female patients need a negative serum or urine pregnancy test within 7 days of study enrollment (applies only if patient is of childbearing potential. Non-childbearing is defined as >= 1 year postmenopausal or surgically sterilized).
- Patients who are considered to require immediate induction (rapidly rising WBC >/= 50,000 and/or organ involvement as per the assessment of the treating physician) can be treated without final cytogenetic results and pretreatment assessment of cardiac ejection fraction (MUGA or echocardiogram) if by history and physical examination patients have </= NYHA class II disease.
Who cannot join
- AML with the following cytogenetic abnormalities: t(15;17), t(8;21), inv(16). Cytogenetic results do not need to be available if immediate induction is required (see inclusion #7).
- Cardiac ejection fraction < 30%. Pretreatment assessment of ejection fraction is not necessary if immediate induction is required as long as by history and physical examination patients have </= NYHA class II disease (see inclusion #7).
- Active and uncontrolled infection or any other severe concurrent disease considered life-threatening, or which, in the judgement of the investigator and after discussion with the Principal Investigator, would make the patient inappropriate for entry into the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
The University of Texas M.D. Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: A Phase II Study of Clofarabine in Combination With Cytarabine (Ara-C) in Patients >/= 50 Years With Newly Diagnosed and Previously Untreated Acute Myeloid Leukemia (AML) and High-risk Myelodysplastic Syndrome (MDS) (>/= 10% Bone Marrow Blasts)
The goal of this clinical research study is to learn if clofarabine, when given in combination with ara-C (cytarabine), can help to improve the disease's response to therapy and to increase the duration of response in patients who are 50 years or older with leukemia. The safety of this combination treatment will also be studied.
Read the detailed description
The treatment of acute myeloid leukemia (AML) in older patients has not improved significantly in recent years when compared with the considerable progress that has been made in younger patients. Hence, new drugs and approaches are needed in this poor-prognosis group of patients with AML.
Nucleoside analogs are among the most active antileukemic agents available. Clofarabine was synthesized as a rational extension of the experience with other deoxyadenosine analogs. Clofarabine is converted to the monophosphate form by the enzyme deoxycytidine kinase which represents the major metabolite of clofarabine. Phosphorylation of clofarabine is substantially more efficient than that of other nucleosides such as fludarabine and so is intracellular retention of the triphosphate form of clofarabine. Mechanisms of action include inhibition of DNA synthesis, inhibition of DNA polymerases, and potent inhibition of ribonucleotide reductase (RNR) resulting in depletion of normal nucleotides and increased DNA uptake of the analog. Single agent clofarabine has shown activity in phase I studies in AML and ALL. As a potent inhibitor of RNR, however, clofarabine is ideal to be incorporated into biochemical modulation strategies such as have been tested and validated with fludarabine and ara-C in AML. By combining clofarabine with ara-C, inhibition of RNR by clofarabine will result in a drop of deoxynucleotides causing a decrease in the feedback inhibition of deoxycytidine kinase which is the rate-limiting step in the synthesis of ara-CTP leading to increased retention of ara-CTP. Therefore, the activity of clofarabine and ara-C in leukemic cells would be complemented by a biochemical synergism between these agents that should result in better clinical efficacy. We have established the safety of the combination in salvage patients with acute leukemias.
- Conditions
- Leukemia, Myeloid, Myelodysplastic Syndromes
- Being tested
- clofarabine, Ara-C
- Keywords
- Newly diagnosed and previously untreated acute myeloid leukemia (AML), High-risk myelodysplastic syndrome (MDS) (>/= 10% bone marrow blasts), Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS)
- Medical subject headings
- Leukemia, Myeloid, Myelodysplastic Syndromes, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
clofarabineDrug
Ara-CDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2003 (estimated)
- Study start23 Jun 2003
- Primary completion22 Feb 2006
- Study completion22 Feb 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leukemia, MyeloidStudies of the same condition, open and under way.
- More trials run by M.D. Anderson 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Genzyme, a Sanofi Company
- Responsible party
- Sponsor
- Investigators
- Stefan Faderl, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00065143
- Sponsor's protocol ID
- ID03-0139
- Status last verified
- Nov 2018
- First submitted
- 17 Jul 2003
- Last updated
- 7 Nov 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Clofarabine in Combination With Cytarabine (Ara-C) in Patients >/= 50 Years With Newly Diagnosed and Previously Untreated Acute Myeloid Leukemia (AML) and High-risk Myelodysplastic Syndrome (MDS) (>/= 10% Bone Marrow Blasts)
- ClinicalTrials.gov ID
- NCT00065143
- Acronym / sponsor ID
- ID03-0139
- Conditions
- Leukemia, Myeloid, Myelodysplastic Syndromes
- Keywords
- Newly diagnosed and previously untreated acute myeloid leukemia (AML), High-risk myelodysplastic syndrome (MDS) (>/= 10% bone marrow blasts), Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Genzyme, a Sanofi Company
- Study start
- 23 Jun 2003 (actual)
- Primary completion
- 22 Feb 2006 (actual)
- Study completion
- 22 Feb 2006 (actual)
- First posted
- 18 Jul 2003 (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 goal of this clinical research study is to learn if clofarabine, when given in combination with ara-C (cytarabine), can help to improve the disease's response to therapy and to increase the duration of response in patients who are 50 years or older with leukemia. The safety of this combination treatment will also be studied.
Detailed description
The treatment of acute myeloid leukemia (AML) in older patients has not improved significantly in recent years when compared with the considerable progress that has been made in younger patients. Hence, new drugs and approaches are needed in this poor-prognosis group of patients with AML.
Nucleoside analogs are among the most active antileukemic agents available. Clofarabine was synthesized as a rational extension of the experience with other deoxyadenosine analogs. Clofarabine is converted to the monophosphate form by the enzyme deoxycytidine kinase which represents the major metabolite of clofarabine. Phosphorylation of clofarabine is substantially more efficient than that of other nucleosides such as fludarabine and so is intracellular retention of the triphosphate form of clofarabine. Mechanisms of action include inhibition of DNA synthesis, inhibition of DNA polymerases, and potent inhibition of ribonucleotide reductase (RNR) resulting in depletion of normal nucleotides and increased DNA uptake of the analog. Single agent clofarabine has shown activity in phase I studies in AML and ALL. As a potent inhibitor of RNR, however, clofarabine is ideal to be incorporated into biochemical modulation strategies such as have been tested and validated with fludarabine and ara-C in AML. By combining clofarabine with ara-C, inhibition of RNR by clofarabine will result in a drop of deoxynucleotides causing a decrease in the feedback inhibition of deoxycytidine kinase which is the rate-limiting step in the synthesis of ara-CTP leading to increased retention of ara-CTP. Therefore, the activity of clofarabine and ara-C in leukemic cells would be complemented by a biochemical synergism between these agents that should result in better clinical efficacy. We have established the safety of the combination in salvage patients with acute leukemias.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 50 to 74 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Previously untreated acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) (> 10% blasts). Prior therapy with hydroxyurea, single agent chemotherapy (e.g. decitabine), hematopoietic growth factors, biological or "targeted" therapies are allowed.
- Age > 50 years to < 74 years (diploid cytogenetics) and < 69 years (abnormal cytogenetics).
- ECOG performance status </= 2.
- Sign a written informed consent form.
- Adequate liver function (total bilirubin < 2mg/dL, SGPT or SGOT < x 4 ULN) and renal function (serum creatinine < 2mg/dL).
Key exclusion criteria (3 listed)
- AML with the following cytogenetic abnormalities: t(15;17), t(8;21), inv(16). Cytogenetic results do not need to be available if immediate induction is required (see inclusion #7).
- Cardiac ejection fraction < 30%. Pretreatment assessment of ejection fraction is not necessary if immediate induction is required as long as by history and physical examination patients have </= NYHA class II disease (see inclusion #7).
- Active and uncontrolled infection or any other severe concurrent disease considered life-threatening, or which, in the judgement of the investigator and after discussion with the Principal Investigator, would make the patient inappropriate for entry into the study.
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 |
|---|---|---|
| clofarabine | Drug | – |
| Ara-C | Drug | – |
Primary outcome
Not reported in the source record.
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 7 Nov 2018.
- Website for The University of Texas M.D. Anderson Cancer CenterLink provided by the sponsor.
Related trials for Leukemia, Myeloid
RecruitingPhase 1
A Study of CHM-029 in Participants With NPM1 Mutated, KMT2A or NUP98 Rearranged AML
AML (Acute Myeloid Leukemia)
RecruitingPhase 1
Vididencel in CML-CP Patients With MRD
CML (Chronic Myelogenous Leukemia)
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
RecruitingPhase 1/2
Venetoclax and CLAG-M for the Treatment of Acute Myeloid Leukemia and High-Grade Myeloid Neoplasms
Acute Biphenotypic Leukemia, Acute Myeloid 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.
Stefan Faderl, MD principal investigator
M.D. Anderson 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 clofarabine and Ara-C in people with Leukemia, Myeloid and Myelodysplastic Syndromes, run by M.D. Anderson 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 7 inclusion and 3 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 7 Nov 2018. 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?
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.
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 7 Nov 2018.