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TerminatedNCT00593645Updated Sep 12, 2014Results posted

Clofarabine, Cytarabine, and Thymoglobulin for Allogeneic Transplantation

A Phase 2 interventional study of Clofarabine and Cytarabine in Myelodysplastic Syndromes and Acute Myeloid Leukemia, sponsored by Washington University School of Medicine. Terminated at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2014-09-12.

Sponsored by Washington University School of Medicine · Phase 2, Interventional, and Treatment

Why this study was terminated
toxicities were worse than expected
Phase
Phase 2
Study type
Interventional
Enrollment
7
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

This study will test the combination of clofarabine, cytarabine, and thymoglobulin as a non-myeloablative conditioning regimen for patients with myelodysplastic syndromes or acute myeloid leukemia undergoing allogeneic stem cell transplant.

Read the detailed description

Current reduced intensity conditioning regimens have been able to decrease TRM (treatment related mortality) but suffer from increased rates of disease relapse. Disease burden at transplantation, as measured by percent myeloblasts, predicts relapse. Current regimens employ fludarabine and busulfan with various adjutants, but these agents are not part of the usual armamentarium used versus leukemia and have questionable anti-leukemic activity. By substituting clofarabine and cytarabine, a combination with proven anti-leukemic activity in the relapsed and refractory setting as well as activity versus MDS, as the back bone of the regimen we hope overcome residual disease and improve post-transplant relapse rates. Furthermore the principal toxicity of this regimen is myelosuppression, which should be abrogated by the infusion of stem cells. Thymoglobulin is included due to its minimal contribution to toxicity but significant benefits in engraftment, and controlling acute and chronic GVHD, which are major contributors to TRM and disease specific activity in MDS.

02

Conditions studied

  • Myelodysplastic Syndromes
  • Acute Myeloid Leukemia

Keywords

  • Conditioning regimens
  • Stem Cell Transplantation
  • Hematopoietic Stem Cell Transplantation
  • Allogeneic Stem Cell Transplantation
  • Nonmyeloablative conditioning
  • Clofarabine
  • Cytarabine
  • Anti-thymocyte globulin
03

In context

Myelodysplastic Syndromes

2,165 studies on the registry are indexed under Myelodysplastic Syndromes; 322 are open to participants now.

This study's enrollment of 7 is below the median of 39 across 1,771 interventional studies indexed under Myelodysplastic Syndromes.

Browse Myelodysplastic Syndromes studies →

Lead sponsor

Washington University School of Medicine is the lead sponsor of 1,795 studies on the registry; 271 are open to participants now.

Of its 330 completed or terminated interventional studies of FDA-regulated products, 216 (65%) have results posted.

Browse Washington University School of Medicine studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  1. Myelodysplastic Syndrome (MDS), as defined by the World Health Organization criteria, OR Chronic Myelomonocytic Leukemia (CMML) as defined by the French American British classification OR Acute Myeloid Leukemia (AML) in complete remission [excluding FAB-M3] diagnosed by standard criteria and meet the criteria below:

    1. Patients may be in any CR
    2. No more than 2 cycles of consolidation. Any consolidation regimen may be used.
    3. No more than 6 months from documented CR to transplant.
  2. Age 18 years or older.
  3. ECOG performance status \<=2
  4. Identification of suitable donor
  5. DLCO >=40% with no symptomatic pulmonary disease
  6. LVEF by MUGA >= 30%
  7. Serum creatinine \<=1.0 mg/dL; if serum creatinine >1.0 mg/dL, then the estimated glomerular filtration rate (GFR) must be >60 mL/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease equation where Predicted GFR (ml/min/1.73 m2) = 186 x (Serum Creatinine)-1.154 x (age in years)-0.023 x (0.742 if patient is female) x (1.212 if patient is black).
  8. Bilirubin \<=2 times the upper limit of normal
  9. AST \<=3 times the upper limit of normal

Donor criteria:

  1. HLA-Matched Sibling: The donor must be an adequate HLA match as determined by serologic typing for class (A, B) and low resolution molecular typing for class II (DRB1) as defined by institutional standards.
  2. Matched Unrelated Donor: An acceptable match per NMDP standards based on high resolution molecular typing.
  3. The donor must be healthy and must be an acceptable donor as per institutional standards for stem cell collection.
  4. The donor must have no significant cardiopulmonary, renal, endocrine, or hepatic disease.
  5. There is no upper age restriction for donors, but they must be at least 18 years of age.
  6. Syngeneic donors are not eligible.
  7. No known HIV.

Exclusion criteria

Exclusion Criteria:

  1. Pregnant or nursing.
  2. Active systemic infection considered opportunistic, life threatening or clinically significant at the time of treatment.
  3. Severe concurrent disease, including severe insulin-dependent diabetes, uncontrolled hypertension, transient ischemic attacks, uncontrolled symptomatic coronary artery disease, or symptomatic CNS involvement or psychiatric illness/social situations that would limit compliance with study requirements.
  4. Known HIV disease.
  5. History of other malignancy except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast unless the subject has been off treatment and free from disease for > 3 years.
  6. Active disease at the time of transplant.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
7 participants (actual)

Study arms

  • Experimental
    Arm 1: Non-myeloablative conditioning regimen

    * Clofarabine 40mg/m2/day IV over two hours daily x 5 days on Days -6 thru -2 * Cytarabine 1gm/m2/day IV over two hours daily x 5 days on Days -6 thru -2 after the START of Clofarabine. * Thymoglobulin 1.0mg/kg IV over 6 hours X 1 day on Day -4, then 2.5mg/kg/day x 2 days on Days -3 and -2. * Stem Cell Transplant - On day 0 a minimum of total CD34+ cell dose of 2 x10E6/kg (actual weight of recipient) will be infused.

    Drug: Clofarabine · Drug: Cytarabine · Drug: Thymoglobulin · Procedure: Stem cell infusion

Interventions

  • DrugClofarabine

    Also known as: Clolar

  • DrugCytarabine

    Also known as: Ara-C, Cytosar

  • DrugThymoglobulin

    Also known as: Anti-thymocyte globulin

  • ProcedureStem cell infusion

    Also known as: Stem cell transplant, Hematopoietic stem cell transplant, Peripheral blood stem cell transplant, Bone marrow transplant

06

What researchers measure

Primary outcomes

  1. Six-month Treatment Related Mortality

    Time frame: 6 months

Secondary outcomes

  1. Disease Specific Response Rates

    Disease-specific partial response and complete response.

    Time frame: One, three, six and twelve months.

  2. Engraftment as Measured by Percent Donor Chimerism

    Time frame: Day +30

  3. Engraftment as Measured by Percent Donor Chimerism

    Time frame: Day +40-+60

  4. Engraftment as Measured by Percent Donor Chimerism

    Time frame: Day +80-+90

  5. Overall Survival

    Time frame: 5 years from time of restaging

  6. Disease-free Survival

    Disease-free survival is defined as the length of time after treatment ends that the participant survives without any signs or symptoms of that cancer.

    Time frame: 5 years from time of restaging

  7. Rate of Acute Graft-versus-host Disease (GVHD)

    Acute GVHD occurs within 100 days of transplant.

    Time frame: Up to 100 days after transplant

  8. Rate of Chronic Graft-versus-host Disease (GVHD)

    Time frame: 100 days-1 year after transplant

  9. Use Conventional STR-PCR Method for Monitoring Engraftment

    Includes assessment of mixed chimerism in the whole blood, myeloid cells, T cells, and B cells.

    Time frame: Up to 1 year after transplant

  10. Median Time to Progression

    Time to progression is defined as the length of time from the start of treatment until the disease starts to get worse or spread to other parts of the body.

    Time frame: 5 years from time of restaging

07

Results

Posted Sep 12, 2014
Limitations and caveats
Enrollment was halted after 3 of the first 7 patients expired on days 15/26/32. Predefined early stopping rules were defined that if three deaths occurred in the first 11 patients then it was unlikely to achieve a low treatment-related mortality.

Participant flow

Enrollment to the study opened on 11/21/2007 and enrollment to the study closed on 08/11/2008

Participant flow — Overall Study
MilestoneArm 1: Non-myeloablative Conditioning Regimen
Started7
Completed7
Not completed0

Outcome measures

PrimarySix-month Treatment Related Mortality
Time frame:
6 months

No measurements were reported for this outcome.

SecondaryDisease Specific Response Rates

Disease-specific partial response and complete response.

Time frame:
One, three, six and twelve months.

No measurements were reported for this outcome.

SecondaryEngraftment as Measured by Percent Donor Chimerism
Time frame:
Day +30
Reported as:
Number · participants
Engraftment as Measured by Percent Donor Chimerism
participantsArm 1: Non-myeloablative Conditioning Regimen
Not done2
50% donor (bone marrow)1
100% donor (bone marrow)1
23.5% donor (FISH)1
SecondaryEngraftment as Measured by Percent Donor Chimerism
Time frame:
Day +40-+60
Reported as:
Number · participants
Engraftment as Measured by Percent Donor Chimerism
participantsArm 1: Non-myeloablative Conditioning Regimen
60% donor (bone marrow)1
70% donor (bone marrow)1
75% donor (bone marrow)1
100% donor (peripheral blood)1
SecondaryEngraftment as Measured by Percent Donor Chimerism
Time frame:
Day +80-+90
Reported as:
Number · participants
Engraftment as Measured by Percent Donor Chimerism
participantsArm 1: Non-myeloablative Conditioning Regimen
0% donor1
33% donor - myeloid (peripheral blood)1
67% donor (bone marrow)1
100% donor (bone marrow)1
SecondaryOverall Survival
Time frame:
5 years from time of restaging
Reported as:
Median · days
Overall Survival
daysArm 1: Non-myeloablative Conditioning Regimen
Overall Survival237 (15 to 443)
SecondaryDisease-free Survival

Disease-free survival is defined as the length of time after treatment ends that the participant survives without any signs or symptoms of that cancer.

Time frame:
5 years from time of restaging
Reported as:
Number · participants
Disease-free Survival
participantsArm 1: Non-myeloablative Conditioning Regimen
Disease-free Survival0
SecondaryRate of Acute Graft-versus-host Disease (GVHD)

Acute GVHD occurs within 100 days of transplant.

Time frame:
Up to 100 days after transplant
Reported as:
Number · percentage of participants
Rate of Acute Graft-versus-host Disease (GVHD)
percentage of participantsArm 1: Non-myeloablative Conditioning Regimen
Rate of Acute Graft-versus-host Disease (GVHD)0
SecondaryRate of Chronic Graft-versus-host Disease (GVHD)
Time frame:
100 days-1 year after transplant
Reported as:
Number · percentage of participants
Rate of Chronic Graft-versus-host Disease (GVHD)
percentage of participantsArm 1: Non-myeloablative Conditioning Regimen
Rate of Chronic Graft-versus-host Disease (GVHD)0
SecondaryUse Conventional STR-PCR Method for Monitoring Engraftment

Includes assessment of mixed chimerism in the whole blood, myeloid cells, T cells, and B cells.

Time frame:
Up to 1 year after transplant

No measurements were reported for this outcome.

SecondaryMedian Time to Progression

Time to progression is defined as the length of time from the start of treatment until the disease starts to get worse or spread to other parts of the body.

Time frame:
5 years from time of restaging
Reported as:
Median · days
Median Time to Progression
daysArm 1: Non-myeloablative Conditioning Regimen
Median Time to Progression152 (98 to 154)

Adverse events

Collected over Adverse event collection started from the beginning of treatment through 1 year post transplant.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Arm 1—5/7 (71.4%)7/7 (100%)
Most frequent serious events
Showing 10 of 13
Most frequent serious events
EventArm 1
Death due to disease progressionGeneral disorders2/7
BilirubinInvestigations1/7
Chest painCardiac disorders1/7
Death - respiratory failureRespiratory, thoracic and mediastinal disorders1/7
DyspneaRespiratory, thoracic and mediastinal disorders1/7
Erythema multiformeSkin and subcutaneous tissue disorders1/7
HypocalcemiaMetabolism and nutrition disorders1/7
Infection with Gr. 3/4 neutropeniaInfections and infestations1/7
MucositisGastrointestinal disorders1/7
Perforation, GI - colonGastrointestinal disorders1/7
Most frequent other events
Showing 10 of 101
Most frequent other events
EventArm 1
DiarrheaGastrointestinal disorders7/7
Edema:limbGeneral disorders7/7
Extremity painMusculoskeletal and connective tissue disorders7/7
Neutropenic feverInfections and infestations7/7
SGOT (AST)Investigations7/7
SGPT (ALT)Investigations7/7
HypoalbuminemiaInvestigations6/7
HypokalemiaInvestigations6/7
MucositisGastrointestinal disorders6/7
Rash/desquamationSkin and subcutaneous tissue disorders6/7

Baseline characteristics

Age, Continuous
Age, Continuous(years)Arm 1: Non-myeloablative Conditioning Regimen
Median54 (24 to 68)
Sex: Female, Male
Sex: Female, Male(Participants)Arm 1: Non-myeloablative Conditioning Regimen
Female1
Male6
Region of Enrollment
Region of Enrollment(participants)Arm 1: Non-myeloablative Conditioning Regimen
United States7
Diagnosis
Diagnosis(participants)Arm 1: Non-myeloablative Conditioning Regimen
Myelodysplastic syndrome3
Acute myeloid leukemia4
08

Study locations

1 site
  • Ravi Vij, M.D.
    St Louis, Missouri 63110, United States
09

References and documents

10

Timeline

Tracking since Sep 25, 2026
Not marked actual or estimatedDates not marked actual or estimated

The record gives a start of Nov 2007, a primary completion of Dec 2008 and a completion of Jul 2009. It does not say whether these dates are actual or estimated.

Results were first posted in Sep 2014, 5 years 9 months after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered
Jan 2, 2008
First posted
Jan 15, 2008
Start
Nov 2007
Primary completionActual
Dec 2008
CompletionActual
Jul 2009
Results first posted
Sep 12, 2014
Last update
Sep 12, 2014
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Sep 12, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00593645
Lead sponsor
Washington University School of Medicine
Responsible party
Sponsor
First posted
Jan 15, 2008
Start date
Nov 2007
Primary completion
Dec 2008
Completion
Jul 2009
Results posted
Sep 12, 2014
Last update
Sep 12, 2014

Study contacts

Ravi Vij, M.D.
principal investigator · Washington Universtiy of St. Louis

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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