- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00617929
Antithymocyte Globulin, Clofarabine, and Rituximab in Treating Patients After an Unsuccessful Stem Cell Transplant
Conditioning for Graft Failure After Hematopoietic Stem Cell Transplantation
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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
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Minnesota
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Minneapolis, Minnesota, United States, 55455
- Masonic Cancer Center at University of Minnesota
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Conditioning for Graft Failure
Primary or secondary graft failure after hematopoietic stem cell transplantation defined as a > 50% loss of previously best donor chimerism or less than 25% donor chimerism 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.
Patients receive anti-thymocyte globulin, rituximab, and clofarabine.
|
administer 3 mg/kg intravenously (IV) over 4 hours on days -6, -5 and -4.
Other Names:
administered 375 mg/m^2 intravenously (IV) in 1 mg/mL normal saline on day -7.
Other Names:
administered 30 mg/m^2 intravenously (IV) over 1 hour on Days -4, -3, and -2.
Other Names:
administered on Day 0 per institutional guidelines.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Rate of Sustained Donor Engraftment
Time Frame: Day 42 post transplantation
|
Rate of Sustained Donor Engraftment is defined as the percent of paticipants with an absolute neutrophile count (ANC) of 500 or more without a subsequent graft rejection.
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Day 42 post transplantation
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Survival at 100 Days Post Transplant
Time Frame: Day 100 post transplantation
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Percent of patients alive from beginning of study to Day 100 post transplantation
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Day 100 post transplantation
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Treatment-related Death
Time Frame: Day 100 post transplantation
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Percent of patients who died related to the treatment in this study.
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Day 100 post transplantation
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Time to Primary Neutrophil Engraftment
Time Frame: Day 42 post transplantation
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Time to primary neutrophil engraftment is defined as the percent of patients with an absolute neutrophil count (ANC) of 500 or more neutrophils in a cubic millimeter of blood.
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Day 42 post transplantation
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Survival
Time Frame: One year post transplantation
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Percent of patients alive from beginning of study to one year post transplantation
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One year post transplantation
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Chimerism
Time Frame: Day 28 post transplantation
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Occurrence of genetically distinct cell types in a single organism
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Day 28 post transplantation
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Acute Graft-vs-host Disease
Time Frame: Day 30-100
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Percent of patients with Acute Graft-vs-host Disease - a process where T-cells present in the donor's bone marrow at the time of transplant identify the transplant patient as "non-self' and attack the patient's skin, liver, stomach, and/or intestines.
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Day 30-100
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Collaborators and Investigators
Investigators
- Principal Investigator: Jakub Tolar, MD, Masonic Cancer Center, University of Minnesota
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
- stage III malignant testicular germ cell tumor
- stage IV breast cancer
- stage IIIA breast cancer
- stage IIIB breast cancer
- breast cancer
- primary myelofibrosis
- stage III ovarian epithelial cancer
- stage IV ovarian epithelial cancer
- recurrent ovarian epithelial cancer
- stage IIIC breast cancer
- stage III adult diffuse large cell lymphoma
- stage III adult immunoblastic large cell lymphoma
- stage III adult Burkitt lymphoma
- stage IV grade 3 follicular lymphoma
- stage IV adult diffuse large cell lymphoma
- stage IV adult immunoblastic large cell lymphoma
- stage IV adult Burkitt lymphoma
- chronic myelomonocytic leukemia
- de novo myelodysplastic syndromes
- secondary myelodysplastic syndromes
- secondary acute myeloid leukemia
- juvenile myelomonocytic leukemia
- recurrent/refractory childhood Hodgkin lymphoma
- rhabdomyosarcoma
- relapsing chronic myelogenous leukemia
- acute myeloid leukemia
- stage III grade 1 follicular lymphoma
- stage III grade 2 follicular lymphoma
- stage III grade 3 follicular lymphoma
- stage III adult diffuse small cleaved cell lymphoma
- stage III adult diffuse mixed cell lymphoma
- stage IV grade 1 follicular lymphoma
- stage IV grade 2 follicular lymphoma
- stage IV adult diffuse small cleaved cell lymphoma
- stage IV adult diffuse mixed cell lymphoma
- stage III mantle cell lymphoma
- stage IV mantle cell lymphoma
- stage II multiple myeloma
- stage III multiple myeloma
- Hodgkin lymphoma
- recurrent small lymphocytic lymphoma
- stage III small lymphocytic lymphoma
- stage III marginal zone lymphoma
- stage IV small lymphocytic lymphoma
- stage IV marginal zone lymphoma
- splenic marginal zone lymphoma
- stage I multiple myeloma
- refractory chronic lymphocytic leukemia
- stage III chronic lymphocytic leukemia
- stage IV chronic lymphocytic leukemia
- stage III adult Hodgkin lymphoma
- stage IV adult Hodgkin lymphoma
- stage III adult lymphoblastic lymphoma
- stage IV adult lymphoblastic lymphoma
- disseminated neuroblastoma
- recurrent neuroblastoma
- refractory multiple myeloma
- refractory hairy cell leukemia
- chronic myeloid leukemia
- stage II ovarian epithelial cancer
- acute lymphoblastic leukemia
- recurrent ovarian germ cell tumor
- chronic eosinophilic leukemia
- chronic neutrophilic leukemia
- recurrent malignant testicular germ cell tumor
- mantle cell lymphoma
- follicular lymphoma
- recurrent Wilms tumor and other childhood kidney tumors
- myelodysplastic syndromes
- marginal zone lymphoma
- Burkitt lymphoma
- chronic myelogenous leukemia
- lymphoblastic leukemia
- lymphoblastic lymphoma
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Immunological
- Clofarabine
- Rituximab
- Thymoglobulin
- Antilymphocyte Serum
Other Study ID Numbers
- 2007LS072
- UMN-MT2007-07 (Other Identifier: Blood and Marrow Transplantation Program)
- 0707M11845 (Other Identifier: IRB, University of Minnesota)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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