CancerPhase 2NCT00617929
Antithymocyte Globulin, Clofarabine, and Rituximab in Treating Patients After an Unsuccessful Stem Cell Transplant
A Phase 2 study testing anti-thymocyte globulin, rituximab and clofarabine in people with Cancer, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Cancer
- What is being tested?
- anti-thymocyte globulin, rituximab and clofarabine
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2008to Oct 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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
Trial locations and contacts
1 site in 1 country.
United States1 site
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, 55455
About this study
Official title: 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.
Read the 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.
- Conditions
- Cancer
- Being tested
- anti-thymocyte globulin, rituximab, clofarabine, stem cell transplantation
- Keywords
- chronic myelogenous leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, lymphoblastic leukemia, acute myeloid leukemia, chronic eosinophilic leukemia, primary myelofibrosis, chronic myelomonocytic leukemia, chronic neutrophilic leukemia, de novo myelodysplastic syndromes, disseminated neuroblastoma, juvenile myelomonocytic leukemia, Burkitt lymphoma, rhabdomyosarcoma, myelodysplastic syndromes, Hodgkin lymphoma, lymphoblastic lymphoma, breast cancer, follicular lymphoma, mantle cell lymphoma
- Medical subject headings
- Neoplasms, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Pdgfra-Associated Chronic Eosinophilic Leukemia, Primary Myelofibrosis, Leukemia, Myelomonocytic, Chronic, Leukemia, Neutrophilic, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anti-thymocyte globulinBiological
Also called Thymoglobulin®
administer 3 mg/kg intravenously (IV) over 4 hours on days -6, -5 and -4.
rituximabBiological
Also called Rituxan(R)
administered 375 mg/m^2 intravenously (IV) in 1 mg/mL normal saline on day -7.
clofarabineDrug
Also called CLOLAR™
administered 30 mg/m^2 intravenously (IV) over 1 hour on Days -4, -3, and -2.
stem cell transplantationProcedure or surgery
administered on Day 0 per institutional guidelines.
| Study group | Role | What they receive |
|---|---|---|
| Conditioning for Graft Failure | Experimental | 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. Receives: Biological: anti-thymocyte globulin; Biological: rituximab; Drug: clofarabine; Procedure: stem cell transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of Sustained Donor Engraftment
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.
Measured: Day 42 post transplantation
Survival at 100 Days Post Transplant
Percent of patients alive from beginning of study to Day 100 post transplantation
Measured: Day 100 post transplantation
Secondary outcomes (5)
Treatment-related Death
Percent of patients who died related to the treatment in this study.
Measured: Day 100 post transplantation
Time to Primary Neutrophil Engraftment
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.
Measured: Day 42 post transplantation
Survival
Percent of patients alive from beginning of study to one year post transplantation
Measured: One year post transplantation
Chimerism
Occurrence of genetically distinct cell types in a single organism
Measured: Day 28 post transplantation
Acute Graft-vs-host Disease
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.
Measured: Day 30-100
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2008 (estimated)
- Study startJan 2008
- Primary completionOct 2014
- Study completionOct 2015
Why it stopped: Replaced by another protocol
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for CancerStudies of the same condition, open and under way.
- More trials run by Masonic Cancer Center, University of MinnesotaThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Masonic Cancer Center, University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jakub Tolar, MD, Principal investigator, Masonic Cancer Center, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00617929
- Sponsor's protocol ID
- 2007LS072
- Other IDs
- UMN-MT2007-07, 0707M11845
- Status last verified
- Dec 2017
- First submitted
- 15 Feb 2008
- Last updated
- 28 Dec 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Conditioning for Graft Failure After Hematopoietic Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT00617929
- Acronym / sponsor ID
- 2007LS072
- Conditions
- Cancer
- Keywords
- chronic myelogenous leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, lymphoblastic leukemia, acute myeloid leukemia, chronic eosinophilic leukemia, primary myelofibrosis, chronic myelomonocytic leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Replaced by another protocol
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Masonic Cancer Center, University of MinnesotaUniversity, hospital or other
- Study start
- Jan 2008
- Primary completion
- Oct 2014 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 18 Feb 2008 (estimated)
- Results
- Posted 20 Jan 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Conditioning for Graft Failure | Experimental | Biological: anti-thymocyte globulin, Biological: rituximab, Drug: clofarabine, Procedure: stem cell transplantationPrimary 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. |
Who may qualify
- 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 |
|---|---|---|
| anti-thymocyte globulinAlso: Thymoglobulin®administer 3 mg/kg intravenously (IV) over 4 hours on days -6, -5 and -4. | Biological | Conditioning for Graft Failure |
| rituximabAlso: Rituxan(R)administered 375 mg/m^2 intravenously (IV) in 1 mg/mL normal saline on day -7. | Biological | Conditioning for Graft Failure |
| clofarabineAlso: CLOLAR™administered 30 mg/m^2 intravenously (IV) over 1 hour on Days -4, -3, and -2. | Drug | Conditioning for Graft Failure |
| stem cell transplantationadministered on Day 0 per institutional guidelines. | Procedure or surgery | Conditioning for Graft Failure |
Primary outcome
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.
Survival at 100 Days Post Transplant
Time frame: Day 100 post transplantation
Percent of patients alive from beginning of study to Day 100 post transplantation
5 secondary outcomes
Treatment-related Death
Time frame: Day 100 post transplantation
Time to Primary Neutrophil Engraftment
Time frame: Day 42 post transplantation
Survival
Time frame: One year post transplantation
Chimerism
Time frame: Day 28 post transplantation
Acute Graft-vs-host Disease
Time frame: Day 30-100
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Dec 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Jakub Tolar, MD principal investigator
Masonic Cancer Center, University of Minnesota
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 anti-thymocyte globulin, rituximab and clofarabine in people with Cancer, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Dec 2017. 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?
Yes. Results are posted in the registry (first posted 20 Jan 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Rate of Sustained Donor Engraftment (time frame: Day 42 post transplantation). The study lists 2 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 28 Dec 2017.