LeukemiaPhase 1NCT00641030
Clofarabine and High-Dose Melphalan Followed by Donor Stem Cell Transplant in Patients With Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, or Myelodysplastic Syndromes
A Phase 1 study testing clofarabine, melphalan and gene expression analysis in people with Leukemia and Myelodysplastic Syndromes, run by City of Hope Medical Center at 1 site in United States.
Trial summary
RATIONALE: Giving chemotherapy, such as clofarabine and melphalan, before a donor stem cell transplant helps stop the growth of cancer or abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. Read more about this study
- Who is it for?
- Ages 1 year to 120 years
- Conditions the study is for
- Leukemia, Myelodysplastic Syndromes
- What is being tested?
- clofarabine, melphalan and gene expression analysis
- Type of treatment
- Injection or infusion, Surgery or procedure
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Jul 2007to 1 Jan 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 1 year to 120 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
DISEASE CHARACTERISTICS:
- Diagnosis of one of the following:
- Acute myeloid leukemia
- Acute lymphocytic leukemia
- Myelodysplastic syndromes
- Disease meets 1 of the following criteria:
- In first complete remission (CR)
- In second CR
- In relapse
- No more than 50% blasts in bone marrow
- Not deemed eligible for standard transplantation regimens by the attending physician, or at high risk for relapse
- No suspected or proven CNS leukemia
- HLA-matched (6/6) sibling donor available
PATIENT CHARACTERISTICS:
- Karnofsky performance status 50-100%
- Glomerular filtration rate (pediatric patients) or creatinine clearance ≥ 60 mL/min OR serum creatinine < 1.5 times upper limit of normal (ULN)
- Serum bilirubin ≤ 2.0 mg/dL
- AST and ALT ≤ 2.5 times ULN
- LVEF ≥ 50% by ECHO or MUGA scan
- DLCO or FEV_1 ≥ 40% predicted
- Not pregnant
- Negative pregnancy test
- No concurrent uncontrolled illness including, but not limited to, any of the following:
- Ongoing, active, or poorly controlled infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Poorly controlled pulmonary disease
- Psychiatric illness/social situation that would limit compliance with study requirement
- No active cytomegalovirus (CMV) or fungal disease
- HIV negative
PRIOR CONCURRENT THERAPY:
- Recovered from prior intensive chemotherapy (pediatric patients)
- At least 100 days since prior autologous stem cell transplantation
- At least 100 days since prior radiotherapy administered as part of a transplantation conditioning regimen
- At least 4 weeks since prior chemotherapy
- At least 24 hours since prior hydroxyurea for blast count control
Trial locations and contacts
1 site in 1 country.
United States1 site
City of Hope Comprehensive Cancer Center
Duarte, California, 91010-3000
About this study
Official title: A Phase I Study of Clofarabine Plus High Dose Melphalan as a Conditioning Regimen for Allogeneic Transplantation
RATIONALE: Giving chemotherapy, such as clofarabine and melphalan, before a donor stem cell transplant helps stop the growth of cancer or abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient, they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.
PURPOSE: This phase I trial is studying the side effects and best dose of clofarabine when given together with high-dose melphalan followed by a donor stem cell transplant in treating patients with acute myeloid leukemia, acute lymphocytic leukemia, or myelodysplastic syndromes.
Read the detailed description
OBJECTIVES:
- To determine the maximum tolerated dose and toxicities of clofarabine when administered with high-dose melphalan as a conditioning regimen in patients undergoing allogeneic stem cell transplantation for acute myeloid leukemia, acute lymphocytic leukemia, or myelodysplastic syndromes.
- To assess the efficacy of this regimen in facilitating engraftment in these patients.
- To perform correlative laboratory studies of engraftment, immune reconstitution, and therapeutic outcomes.
OUTLINE: This is a dose-escalation study of clofarabine. Patients are stratified according to age (< 18 years vs ≥ 18 years).
- Reduced-intensity conditioning regimen: Patients receive clofarabine IV over 30 minutes on days -9 to -5 and high-dose melphalan IV over 30 minutes on day -4.
Cohorts of 3-6 patients receive escalating doses of clofarabine 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. At least 6 patients are treated at the MTD.
- Allogeneic stem cell transplantation: Patients undergo allogeneic stem cell transplantation on day 0.
- Graft-versus-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV over 10 hours or orally twice daily beginning on day -1 and continuing until day 90-100, followed by a taper in the absence of GVHD. Patients also receive mycophenolate mofetil IV or orally twice daily beginning on day 0 and continuing until day 28, followed by a taper in the absence of GVHD.
Patients undergo blood and/or bone marrow sample collection periodically for correlative laboratory studies. Samples are examined for markers of immune reconstitution (i.e., CD8+ T lymphocytes, CD4+ T lymphocytes, NK cells, B cells, and monocytes) by flow cytometry and for diversity of the reconstituted T-cell repertoire by PCR-based T-cell receptor repertoire analysis. Samples are also examined for gene expression of hRRM2 and markers of apoptosis (i.e., Bcl-2, Bid, NFkB2, and Bcl-3) by real-time RT-PCR and for markers of ribonucleotide reductase inhibition (i.e., dCTP levels in circulating peripheral blood mononuclear cells).
After completion of study therapy, patients are followed periodically for up to 5 years.
- Conditions
- Leukemia, Myelodysplastic Syndromes
- Being tested
- clofarabine, melphalan, gene expression analysis, reverse transcriptase-polymerase chain reaction, flow cytometry
- Keywords
- de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, adult acute lymphoblastic leukemia in remission, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(15;17)(q22;q12), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), adult acute myeloid leukemia in remission, recurrent adult acute myeloid leukemia, childhood acute myeloid leukemia in remission, recurrent childhood acute myeloid leukemia, secondary acute myeloid leukemia, childhood myelodysplastic syndromes, recurrent adult acute lymphoblastic leukemia, recurrent childhood acute lymphoblastic leukemia, childhood acute lymphoblastic leukemia in remission
- Medical subject headings
- Leukemia, Myelodysplastic Syndromes, Congenital Abnormalities, Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
clofarabineDrug
Administered at the appropriate dose level(dose level one = 30 mg/m2, dose level two and three = 40 mg/m2)on days -9 to day -5 from transplant
melphalanDrug
Administered at the appropriate dose level (dose level one and two = 100 mg/m2, dose level three = 140 mg/m2) on day -4 from transplant
gene expression analysisGenetic
Peripheral blood draw on day -9 and day -4 prior to transplant
reverse transcriptase-polymerase chain reactionGenetic
Peripheral blood draw on day -9 and day -4 prior to transplant
flow cytometryOther
Bone marrow aspirate and biopsy to confirm diagnosis prior to transplant, day -9 pre-transplant, day 30 post-transplant, day 100 post-transplant, 6 months post-transplant, one year post-transplant, then yearly through year 5 post-transplant
laboratory biomarker analysisOther
Peripheral blood draw day -9 or earlier pre-transplant, day 14 post-transplant, day 30 post-transplant, day 60 post-transplant, day 100 post-transplant, 6 months and one year post-transplant.
allogeneic hematopoietic stem cell transplantationProcedure or surgery
Infusion of allogeneic hematopoietic stem cells on day 0 of transplant
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose
Measured: 4 weeks from the start of treatment
Dose-limiting toxicity as assessed by NCI CTCAE v3.0 and the Modified Bearman scale
Measured: 4 weeks from the start of treatment
Graft failure or rejection
Measured: 35 days post-transplant
Secondary outcomes (2)
Efficacy
Measured: One year post-transplant
Correlative laboratory studies of engraftment, immune reconstitution, and therapeutic outcomes
Measured: One year post-transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2008 (estimated)
- Study start27 Jul 2007
- Primary completion1 Jan 2011
- Study completion1 Jan 2011
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 City of Hope Medical 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
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Anthony Stein, MD, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00641030
- Sponsor's protocol ID
- 06114
- Other IDs
- P30CA033572, CHNMC-06114, CDR0000589304
- Status last verified
- Oct 2026
- First submitted
- 20 Mar 2008
- Last updated
- 19 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Clofarabine Plus High Dose Melphalan as a Conditioning Regimen for Allogeneic Transplantation
- ClinicalTrials.gov ID
- NCT00641030
- Acronym / sponsor ID
- 06114
- Conditions
- Leukemia, Myelodysplastic Syndromes
- Keywords
- de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, adult acute lymphoblastic leukemia in remission, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(15;17)(q22;q12), adult acute myeloid leukemia with t(16;16)(p13;q22)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- City of Hope Medical CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 27 Jul 2007 (actual)
- Primary completion
- 1 Jan 2011 (actual)
- Study completion
- 1 Jan 2011 (actual)
- First posted
- 21 Mar 2008 (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.
RATIONALE: Giving chemotherapy, such as clofarabine and melphalan, before a donor stem cell transplant helps stop the growth of cancer or abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient, they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.
PURPOSE: This phase I trial is studying the side effects and best dose of clofarabine when given together with high-dose melphalan followed by a donor stem cell transplant in treating patients with acute myeloid leukemia, acute lymphocytic leukemia, or myelodysplastic syndromes.
Detailed description
OBJECTIVES:
- To determine the maximum tolerated dose and toxicities of clofarabine when administered with high-dose melphalan as a conditioning regimen in patients undergoing allogeneic stem cell transplantation for acute myeloid leukemia, acute lymphocytic leukemia, or myelodysplastic syndromes.
- To assess the efficacy of this regimen in facilitating engraftment in these patients.
- To perform correlative laboratory studies of engraftment, immune reconstitution, and therapeutic outcomes.
OUTLINE: This is a dose-escalation study of clofarabine. Patients are stratified according to age (< 18 years vs ≥ 18 years).
- Reduced-intensity conditioning regimen: Patients receive clofarabine IV over 30 minutes on days -9 to -5 and high-dose melphalan IV over 30 minutes on day -4.
Cohorts of 3-6 patients receive escalating doses of clofarabine 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. At least 6 patients are treated at the MTD.
- Allogeneic stem cell transplantation: Patients undergo allogeneic stem cell transplantation on day 0.
- Graft-versus-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV over 10 hours or orally twice daily beginning on day -1 and continuing until day 90-100, followed by a taper in the absence of GVHD. Patients also receive mycophenolate mofetil IV or orally twice daily beginning on day 0 and continuing until day 28, followed by a taper in the absence of GVHD.
Patients undergo blood and/or bone marrow sample collection periodically for correlative laboratory studies. Samples are examined for markers of immune reconstitution (i.e., CD8+ T lymphocytes, CD4+ T lymphocytes, NK cells, B cells, and monocytes) by flow cytometry and for diversity of the reconstituted T-cell repertoire by PCR-based T-cell receptor repertoire analysis. Samples are also examined for gene expression of hRRM2 and markers of apoptosis (i.e., Bcl-2, Bid, NFkB2, and Bcl-3) by real-time RT-PCR and for markers of ribonucleotide reductase inhibition (i.e., dCTP levels in circulating peripheral blood mononuclear cells).
After completion of study therapy, patients are followed periodically for up to 5 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 1 year to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
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 |
|---|---|---|
| clofarabineAdministered at the appropriate dose level(dose level one = 30 mg/m2, dose level two and three = 40 mg/m2)on days -9 to day -5 from transplant | Drug | – |
| melphalanAdministered at the appropriate dose level (dose level one and two = 100 mg/m2, dose level three = 140 mg/m2) on day -4 from transplant | Drug | – |
| gene expression analysisPeripheral blood draw on day -9 and day -4 prior to transplant | Genetic | – |
| reverse transcriptase-polymerase chain reactionPeripheral blood draw on day -9 and day -4 prior to transplant | Genetic | – |
| flow cytometryBone marrow aspirate and biopsy to confirm diagnosis prior to transplant, day -9 pre-transplant, day 30 post-transplant, day 100 post-transplant, 6 months post-transplant, one year post-transplant, then yearly through year 5 post-transplant | Other | – |
| laboratory biomarker analysisPeripheral blood draw day -9 or earlier pre-transplant, day 14 post-transplant, day 30 post-transplant, day 60 post-transplant, day 100 post-transplant, 6 months and one year post-transplant. | Other | – |
| allogeneic hematopoietic stem cell transplantationInfusion of allogeneic hematopoietic stem cells on day 0 of transplant | Procedure or surgery | – |
Primary outcome
Maximum tolerated dose
Time frame: 4 weeks from the start of treatment
Dose-limiting toxicity as assessed by NCI CTCAE v3.0 and the Modified Bearman scale
Time frame: 4 weeks from the start of treatment
Graft failure or rejection
Time frame: 35 days post-transplant
2 secondary outcomes
Efficacy
Time frame: One year post-transplant
Correlative laboratory studies of engraftment, immune reconstitution, and therapeutic outcomes
Time frame: One year post-transplant
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 19 Oct 2026.
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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.
Anthony Stein, MD principal investigator
City of Hope Medical 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 clofarabine, melphalan and gene expression analysis in people with Leukemia and Myelodysplastic Syndromes, run by City of Hope Medical 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?
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 19 Oct 2026. 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?
Maximum tolerated dose (time frame: 4 weeks from the start of treatment). The study lists 3 primary outcomes in all. 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 19 Oct 2026.