LeukemiaPhase 2NCT00416884
Flu,Alemtuzumab,and TBI Followed By Donor Stem Cell Chronic Phase CML
A Phase 2 study testing Campath, Fludarabine and Total Body Irradiation (TBI) in people with Leukemia, run by OHSU Knight Cancer Institute at 1 site in United States.
Trial summary
RATIONALE: Giving low doses of chemotherapy, such as fludarabine, and total-body irradiation (TBI) before a donor stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. Read more about this study
- Who is it for?
- Ages 4 to 75 years
- Conditions the study is for
- Leukemia
- What is being tested?
- Campath, Fludarabine and Total Body Irradiation (TBI)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- May 2003to Mar 2008
- 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 4 to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients aged 4-75 with chronic myelogenous leukemia (CML) treatable by allogeneic hematopoietic stem cell transplant.
- Patients with cytogenetically confirmed chronic phase CML.
- o Hematologic parameters for chronic phase are: i) Percentage of blasts in peripheral blood or marrow < 15% ii) Percentage of blasts + promyelocytes in the peripheral blood or bone marrow < 30% iii) Percentage of basophils in blood or marrow <20% iv) Platelet count > 100 x 109/l
- Patients must have demonstrated refractoriness/resistance to STI571 defined as follows:
- Hematologically resistant- failure to achieve a complete hematologic remission (CHR) despite 3 months of STI571 therapy.
- Hematologically refractory - a rising WBC count > 20 x 109/l confirmed by two samples taken two weeks apart in a patient with a previous CHR despite concurrent treatment with STI571 iii) Cytogenetically resistant - bone marrow cytogenetics showing > 65% Philadelphia chromosome positivity (Ph+) after 6 months of STI571 based therapy.
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- Cytogenetically refractory - An increase in the number of Philadelphia chromosome positive (Ph+) bone marrow cells by at least 30%, or an increase to > 65%, confirmed by samples at least 1 month apart following a previous STI571 induced cytogenetic response, while continuing STI571 therapy.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
- Patients with a human leukocyte antigen (HLA) matched sibling donor at the HLA-A, B, and DR loci.
- Patients with an unrelated hematopoietic stem cell donor must be matched using high resolution typing for class II human leukocyte antigen (HLA-DR beta-1, 3, 4, 5 and DQ beta-1) and matched with intermediate to high resolution molecular typing at class I human leukocyte antigen (HLA-A, B, and C) loci.
- Patients with accelerated or blast crisis of CML who have returned to chronic phase as described above are eligible.
- Written informed, voluntary consent.
- Sibling donors are permitted if matched at class I human leukocyte antigen (HLA-A, B), and class II human leukocyte antigen (DR) loci.
- Unrelated donors must be matched for class II human leukocyte antigen(HLA-DR beta-1,2,3,4,5) and class II human leukocyte antigen (DQ beta-1) with high resolution typing and with intermediate resolution molecular typing at class I human leukocyte antigen(HLA-A, B, and C) loci.
- Donors must be eligible to serve as a peripheral stem cell allograft donor. Bone marrow donors will not be permitted on this protocol.
- Donors must be >18 and < 75 years of age.
- Exclusions Criteria for Donors:
- Volunteer donors who wish to serve as bone marrow donors only and refuse exogenous cytokines.
- Donors who are Human immunodeficiency virus (HIV+), Human T-lymphotropic virus (HTLV-1+), or hepatitis Bs Ag+..
- Donors with medical conditions that would result in increased risk for Granulocyte colony-stimulating factor (G-CSF) mobilization and harvest of peripheral blood stem cells (PBSC) including renal insufficiency with Cr > 2.0, idiopathic splenomegaly, underlying coagulopathy, uncontrolled coronary artery disease, and major surgery within 28 days.
Who cannot join
- Patients who have received another investigational drug within 30 days.
- Fertile men unwilling to use contraceptive techniques during and for 24 months following treatment.
- Females who are pregnant or fertile women unwilling to use contraceptive techniques for two months prior to entering the study and for 24 months following treatment.
- Patients with active bacterial or fungal infections unresponsive to medical therapy.
- Patients with organ dysfunction including cardiac ejection fraction of less than 35% or pulmonary status with a diffusing capacity of the lung for carbon monoxide(DLCO) of less than 40% and/or receiving supplemental oxygen.
- Liver Function Abnormalities: patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, varices, history of bleeding varices, hepatic encephalopathy or chronic viral hepatitis where the total serum bilirubin is greater than 3 mg per deciliter with symptomatic biliary disease.
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- Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable.
- Patients with a history of any prior bone marrow or peripheral blood stem cell transplantation.
- Patients with any other serious, uncontrolled, concomitant medical condition
- HIV positive patients
- Eligibility criteria for donors:
Trial locations and contacts
1 site in 1 country.
United States1 site
OHSU Knight Cancer Institute
Portland, Oregon, 97239-3098
About this study
Official title: Fludarabine, Campath, TBI T-Cell Deplete NMSCT With Post-Transplant T-Cell Infusions for CML Failing Imatinib Therapy With Imatinib (STI571)
RATIONALE: Giving low doses of chemotherapy, such as fludarabine, and total-body irradiation (TBI) before a donor stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) that have been treated in the laboratory after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and alemtuzumab, and removing the T lymphocyte cells(T cells) from the donor cells before transplant, may stop this from happening.
PURPOSE: This clinical trial is studying how well giving fludarabine, alemtuzumab, and total-body irradiation together with donor stem cell transplant and donor white blood cell (WBC) infusion works in treating patients with chronic phase chronic myelogenous leukemia (CML) that did not respond to previous imatinib mesylate.
Read the detailed description
OBJECTIVES:
- Determine the treatment-related mortality in patients with imatinib mesylate-resistant chronic phase chronic myelogenous leukemia treated with nonmyeloablative conditioning comprising fludarabine, alemtuzumab, and total-body irradiation followed by T-cell-depleted allogeneic stem cell transplantation and post-transplantation allogeneic T-cell infusion.
- Determine if donor engraftment can be safely established using partial T-cell depletion with additional T-cell infusions in these patients.
OUTLINE: Patients receive alemtuzumab IV over 5-6 hours on day -8 and fludarabine IV on days -4 to -2. Patients undergo total-body irradiation followed by T-cell-depleted (CD34+ selected) allogeneic stem cell transplantation on day 0. Patients receive allogeneic T-cell infusion on days 30 and 60. Patients also receive cyclosporine twice daily beginning on day -3 and continuing until day 100 followed by a taper until day 177.
PROJECTED ACCRUAL: Not specified.
- Conditions
- Leukemia
- Being tested
- Campath, Fludarabine, Total Body Irradiation (TBI), T-Cell Deplete
- Keywords
- chronic phase chronic myelogenous leukemia, childhood chronic myelogenous leukemia, relapsing chronic myelogenous leukemia
- Medical subject headings
- Leukemia, Leukemia, Myeloid, Chronic-Phase
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CampathDrug
Also called Nonmeylablative Stem Cell Transplant, Mini Transplant
30 mg on day -8 over 5-6 hours
FludarabineDrug
Also called Nonmeylablative Stem Cell Transplant, Mini Transplant
Fludarabine 30 mg/m^2 on day -4 through day -2
Total Body Irradiation (TBI)Radiation
Also called Nonmeylablative Stem Cell Transplant, Mini Transplant
Total body irradiation single fraction 200 cGy at 7 cGy per minute on day 0
T-Cell DepleteOther
Also called Nonmeylablative Stem Cell Transplant, Mini Transplant
Stem cells will be T cell depleted and given on day 0
| Study group | Role | What they receive |
|---|---|---|
| TBI, Campath, Fludarabine T-cell Deplete | Experimental | (Campath) 30 mg on day -8 over 5-6 hours, Fludarabine 30 mg/m^2 on day -4 through day -2, Total body irradiation single fraction 200 cGy at 7 cGy per minute on day 0., Stem cells will be T cell depleted and given on day 0 Receives: Drug: Campath; Drug: Fludarabine; Radiation: Total Body Irradiation (TBI); Other: T-Cell Deplete |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-related Mortality
Treatment related mortality is a consequence of both complications of the preparative regimen and systemic immunological rejection which is manifested as graft versus host disease(GVHD). The preparative regimens which include whole body radiation and/or high dose chemotherapy are complicated by single or multi-organ failure and by prolonged myelosuppression that can lead to infections and bleeding
Measured: lifetime followup, up to 100 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Dec 2006 (estimated)
- Study startMay 2003
- Primary completionMar 2008
- Study completionMar 2008
Why it stopped: Low enrollment
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 LeukemiaStudies of the same condition, open and under way.
- More trials run by OHSU Knight Cancer InstituteThe 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- OHSU Knight Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Richard Maziarz, OHSU Knight Cancer Institute
- Investigators
- Richard Maziarz, MD, Study chair, OHSU Knight Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00416884
- Sponsor's protocol ID
- CDR0000449649
- Other IDs
- OHSU-TPI-02032-L, OHSU-414
- Status last verified
- Jul 2011
- First submitted
- 27 Dec 2006
- Last updated
- 27 Sep 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 27 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fludarabine, Campath, TBI T-Cell Deplete NMSCT With Post-Transplant T-Cell Infusions for CML Failing Imatinib Therapy With Imatinib (STI571)
- ClinicalTrials.gov ID
- NCT00416884
- Acronym / sponsor ID
- CDR0000449649
- Conditions
- Leukemia
- Keywords
- chronic phase chronic myelogenous leukemia, childhood chronic myelogenous leukemia, relapsing chronic myelogenous leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low enrollment
- Enrolment
- 1 participants (actual)
- Lead sponsor
- OHSU Knight Cancer InstituteUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- May 2003
- Primary completion
- Mar 2008 (actual)
- Study completion
- Mar 2008 (actual)
- First posted
- 28 Dec 2006 (estimated)
- Results
- Posted 2 Aug 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Giving low doses of chemotherapy, such as fludarabine, and total-body irradiation (TBI) before a donor stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) that have been treated in the laboratory after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and alemtuzumab, and removing the T lymphocyte cells(T cells) from the donor cells before transplant, may stop this from happening.
PURPOSE: This clinical trial is studying how well giving fludarabine, alemtuzumab, and total-body irradiation together with donor stem cell transplant and donor white blood cell (WBC) infusion works in treating patients with chronic phase chronic myelogenous leukemia (CML) that did not respond to previous imatinib mesylate.
Detailed description
OBJECTIVES:
- Determine the treatment-related mortality in patients with imatinib mesylate-resistant chronic phase chronic myelogenous leukemia treated with nonmyeloablative conditioning comprising fludarabine, alemtuzumab, and total-body irradiation followed by T-cell-depleted allogeneic stem cell transplantation and post-transplantation allogeneic T-cell infusion.
- Determine if donor engraftment can be safely established using partial T-cell depletion with additional T-cell infusions in these patients.
OUTLINE: Patients receive alemtuzumab IV over 5-6 hours on day -8 and fludarabine IV on days -4 to -2. Patients undergo total-body irradiation followed by T-cell-depleted (CD34+ selected) allogeneic stem cell transplantation on day 0. Patients receive allogeneic T-cell infusion on days 30 and 60. Patients also receive cyclosporine twice daily beginning on day -3 and continuing until day 100 followed by a taper until day 177.
PROJECTED ACCRUAL: Not specified.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TBI, Campath, Fludarabine T-cell Deplete | Experimental | Drug: Campath, Drug: Fludarabine, Radiation: Total Body Irradiation (TBI), Other: T-Cell Deplete(Campath) 30 mg on day -8 over 5-6 hours, Fludarabine 30 mg/m^2 on day -4 through day -2, Total body irradiation single fraction 200 cGy at 7 cGy per minute on day 0., Stem cells will be T cell depleted and given on day 0 |
Who may qualify
- Ages
- 4 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (20 listed)
- Patients aged 4-75 with chronic myelogenous leukemia (CML) treatable by allogeneic hematopoietic stem cell transplant.
- Patients with cytogenetically confirmed chronic phase CML.
- o Hematologic parameters for chronic phase are: i) Percentage of blasts in peripheral blood or marrow < 15% ii) Percentage of blasts + promyelocytes in the peripheral blood or bone marrow < 30% iii) Percentage of basophils in blood or marrow <20% iv) Platelet count > 100 x 109/l
- Patients must have demonstrated refractoriness/resistance to STI571 defined as follows:
- Hematologically refractory - a rising WBC count > 20 x 109/l confirmed by two samples taken two weeks apart in a patient with a previous CHR despite concurrent treatment with STI571 iii) Cytogenetically resistant - bone marrow cytogenetics showing > 65% Philadelphia chromosome positivity (Ph+) after 6 months of STI571 based therapy.
Key exclusion criteria (11 listed)
- Patients who have received another investigational drug within 30 days.
- Fertile men unwilling to use contraceptive techniques during and for 24 months following treatment.
- Females who are pregnant or fertile women unwilling to use contraceptive techniques for two months prior to entering the study and for 24 months following treatment.
- Patients with active bacterial or fungal infections unresponsive to medical therapy.
- Patients with organ dysfunction including cardiac ejection fraction of less than 35% or pulmonary status with a diffusing capacity of the lung for carbon monoxide(DLCO) of less than 40% and/or receiving supplemental oxygen.
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 |
|---|---|---|
| CampathAlso: Nonmeylablative Stem Cell Transplant, Mini Transplant30 mg on day -8 over 5-6 hours | Drug | TBI, Campath, Fludarabine T-cell Deplete |
| FludarabineAlso: Nonmeylablative Stem Cell Transplant, Mini TransplantFludarabine 30 mg/m^2 on day -4 through day -2 | Drug | TBI, Campath, Fludarabine T-cell Deplete |
| Total Body Irradiation (TBI)Also: Nonmeylablative Stem Cell Transplant, Mini TransplantTotal body irradiation single fraction 200 cGy at 7 cGy per minute on day 0 | Radiation | TBI, Campath, Fludarabine T-cell Deplete |
| T-Cell DepleteAlso: Nonmeylablative Stem Cell Transplant, Mini TransplantStem cells will be T cell depleted and given on day 0 | Other | TBI, Campath, Fludarabine T-cell Deplete |
Primary outcome
Number of Participants With Treatment-related Mortality
Time frame: lifetime followup, up to 100 years.
Treatment related mortality is a consequence of both complications of the preparative regimen and systemic immunological rejection which is manifested as graft versus host disease(GVHD). The preparative regimens which include whole body radiation and/or high dose chemotherapy are complicated by single or multi-organ failure and by prolonged myelosuppression that can lead to infections and bleeding
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Sep 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.
Richard Maziarz, MD study chair
OHSU Knight Cancer Institute
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 Campath, Fludarabine and Total Body Irradiation (TBI) in people with Leukemia, run by OHSU Knight Cancer Institute 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?
The sponsor lists 20 inclusion and 11 exclusion criteria. 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: stopped early, as of the sponsor's last update on 27 Sep 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 2 Aug 2011). 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?
Number of Participants With Treatment-related Mortality (time frame: lifetime followup, up to 100 years.). 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 27 Sep 2017.