View Clinical Trial (Medical Research Study)
Conditioning for Graft Failure After Hematopoietic Stem Cell Transplantation
| City: |
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Minneapolis |
| State: |
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Minnesota |
| Zip Code: |
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55455 |
| Conditions: |
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Cancer |
| Purpose: |
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RATIONALE: Antithymocyte globulin, clofarabine, and rituximab may stop the patient's immune
system from rejecting the donor's stem cells when they do not exactly match the patient's
blood. The donated stem cells may replace the patient's immune cells and help destroy any
remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a
donor can also make an immune response against the body's normal cells. Giving antithymocyte
globulin before transplant and cyclosporine and mycophenolate mofetil before and after
transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well giving antithymocyte globulin together
with clofarabine and rituximab works in treating patients after an unsuccessful stem cell
transplant.
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| Study Summary: |
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OBJECTIVES:
Primary
- To determine the rate of sustained donor engraftment at 42 days and survival at 100
days post transplantation in patients treated with anti-thymocyte globulin,
clofarabine, and rituximab.
Secondary
- To determine incidence of treatment-related mortality at day 100 post transplantation.
- To determine incidence of neutrophil recovery by day 42 post transplantation.
- To determine survival at day 100 and 1 year post transplantation.
- To determine the proportion of patients with chimerism at day 28 post transplantation.
- To determine incidence and severity of grades II-IV acute graft-vs-host disease by day
100 post transplantation.
OUTLINE:
- Conditioning regimen: Patients receive rituximab intravenously (IV) on day -7,
anti-thymocyte globulin IV over 4-6 hours on days -6 to -4, and clofarabine IV over 1
hour on days -4 to -2.
- Hematopoietic stem cell transplantation (HSCT): Patients undergo HSCT on day 0.
Patients may receive umbilical cord blood, peripheral blood stem cells, or bone marrow
from unrelated or related donors.
- Graft-vs-host disease (GVHD) prophylaxis: Patients receive oral cyclosporine twice
daily or cyclosporine IV every 8 hours beginning on day -3 and continuing for 100 or
180 days post transplantation followed by a taper; mycophenolate mofetil IV every 8
hours beginning on day -3 and continuing for 30 days (or 7 days after engraftment with
no evidence of GVHD); and filgrastim (G-CSF) IV once daily beginning on day 1 and
continuing until blood counts recover.
After completion of study therapy, patients are followed on days 100, 180, and 360.
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| Criteria: |
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Patient Inclusion Criteria:
- Timing of relevant evaluations: Taking in account the need for rapid intervention, if
white blood count is less than 200 on day +20, bone marrow aspirate should be
performed on day +21. Unless there is an increase in absolute neutrophil count (ANC)
to > 500 in the following 7 days, bone marrow aspirate should be repeated on day +28.
If the white blood count is still less than 200 and bone marrow is acellular, bone
marrow (BM) or peripheral blood stem cell (PBSC) donor should be reactivated and
availability of cord blood (CB) units assessed. If the BM or PBSC donor is not
confirmed within 14 days of the request for the donation (typically second donation
from the same donor), CB unit should be used instead.
Primary or secondary graft failure after hematopoietic stem cell transplantation defined
as a > 50% loss of donor chimerism from previous maximum or less than 25% donor beyond day
+42 with pancytopenia and no evidence of relapse. Patients with any diagnosis, type of
donor, hematopoietic cell graft or conditioning regimen should be considered for this
study.
- primary graft failure is defined as:
- ANC < 500
- BM < 10% on two occasions (Day +21 and Day +28)
- Donor chimerism need not to be considered, provided there is no evidence of
malignancy
- secondary graft failure is defined as < 5% cellularity and ANC < 500 for more than 7
days any time after primary engraftment).
- Women of childbearing potential must agree to use adequate contraception
(diaphragm, birth control pills, injections, intrauterine device [IUD], surgical
sterilization, subcutaneous implants, or abstinence, etc.) for the duration of
treatment.
- Patients or their guardian are able and willing to provide written informed
consent.
Patient Exclusion Criteria:
The presence of any of the following excludes a patient from study enrollment:
- Uncontrolled active infection defined as more than one week with no response to
appropriately chosen antibiotics
- Evidence of recurrence of primary malignancy.
- Pregnant or lactating. The agents used in this study may be teratogenic to a fetus
and there is no information on the excretion of agents into breast milk. All females
of childbearing potential must have a blood test or urine study within 2 weeks prior
to registration to rule out pregnancy. Women of childbearing age must use appropriate
methods as described.
- Allergy to rituximab.
- Evidence of HIV infection or positive HIV serology.
- Autologous recovery defined as defined as greater than 90% recipient PCR product in
the competitive VNTR PCR performed on gradually increasing white blood cell count.
Donor Inclusion Criteria:
- Related donors must be 2-75 years of age and in good health.
- Meets match criteria
- Able and willing to undergo cell collection procedures (bone marrow cell collection
or leukapheresis)
- Not pregnant or lactating.
- HIV-1, HIV-2 negative; HTLV-1, HTLV-2 negative, Hepatitis B and C negative.
- Patients or their guardian are able and willing to provide informed consent
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| NCT ID: |
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NCT00617929 |
| Primary Contact: |
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Principal Investigator
Jakub Tolar, MD
Masonic Cancer Center, University of Minnesota
Jakub Tolar, M.D.
Phone: 612-624-7180
Email: tolar003@umn.edu
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| Backup Contact: |
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N/A |
| Location Contact: |
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Minneapolis, Minnesota 55455
United States
Clinical Trials Office - Masonic Cancer Center at University o
Phone: 612-624-2620
Site Status: Recruiting |
| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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May 22, 2013 |
| Modifications to this listing: |
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