LymphomaPhase 1NCT00606437
Total Body Irradiation With Fludarabine Followed by Combined Umbilical Cord Blood (UCB) Transplants
A Phase 1 study testing Total Body Irradiation with Fludarabine in UCB Transplants in people with Lymphoma and Myeloma, run by Duke University at 1 site in United States.
Trial summary
Results to date of umbilical cord blood transplantation in adult and fully mature adolescent patients are inferior to what is seen in children, due to a lower stem cell dosage in adults and a more toxic conditioning regimen. Read more about this study
- Who is it for?
- Ages 14 to 65 years
- What is being tested?
- Total Body Irradiation with Fludarabine in UCB Transplants
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2005to Feb 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 14 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age 14 to 65 years.
- Available cord blood graft.
- Patients with high risk ALL in first complete remission, with high risk being defined by the presence of t(4;11), t(9;22) or t(1;19) or patients presenting with extreme hyperleukocytosis (WBC > 500,000/ul) or partial remission after induction therapy.
- Adult patients with acute non-lymphocytic leukemia (ANLL) in first complete remission with high-risk cytogenetics (monosomy chromosome 5 or 7, del (5q), abn (3q26), complex karyotypic abnormalities) or failure to achieve complete remission after standard induction therapy.
- All patients with ALL or ANLL in second or subsequent remission or partial remission.
- All patients with CML in chronic (failed interferon and/or Gleevec) or accelerated phase.
Show all 25Show fewer
- Patients with myelodysplastic syndrome with International Prognostic Scoring System (IPSS) risk category of INT-1 or greater.
- Patients with severe aplastic anemia must have failed immunosuppressive therapy such as cyclosporine plus anti-thymocyte globulin.
- Non-Hodgkin's lymphoma or Hodgkin's disease:
- High risk disease in first complete or partial remission
- Chemotherapy-resistant relapse
- Second or subsequent relapse or remission
- Myelofibrosis with myeloid metaplasia.
- High risk, congenital immunodeficiency disorders resulting in recurrent (> 3 episodes) life-threatening infection, known to be curable with allogeneic stem cell transplantation (to include, but not limited to; severe combined immunodeficiency disorder, combined immunodeficiency disease, Wiskott-Aldrich syndrome, Chediak-Higashi syndrome, chronic granulomatous disease, leukocyte adhesion deficiency, hemophagocytic lymphohistiocytosis).
- Patients with a history of CNS disease must have been treated and have no active CNS disease at the time of protocol treatment.
- ECOG performance status < or equal to 2.
- Patients must have adequate function of other organ systems as measured by:
- Creatinine clearance (by Cockcroft Gault equation) > or equal to 30 ml/min. Hepatic transaminases (ALT/AST) < or equal to 4 x normal, bilirubin < or equal to 2.0 mg/dl
- Pulmonary function tests demonstrating FVC and FEV1 of > or equal to 50% of predicted for age and DLCO > or equal to 50% of predicted
- Ejection fraction of > or equal to 45% by echocardiogram, radionuclide scan or cardiac MRI
- Patients must be HIV negative.
- They do not have an HLA-ABC/DR identical related bone marrow or UCB donor.
- They do NOT have a 5/6 antigen matched related bone marrow or UCB donor.
- Their condition precludes waiting to search and find a donor in the National Marrow Donor Registry or an 8/8 (HLA-A, B, C, DRB1) antigen by high resolution (allele-level) typing matched unrelated donor was not found.
- Patients must not be pregnant.
Who cannot join
- Patients that have circulating antibodies specific for donor major histocompatibility antigens (as determined by panel of reactive antibody assay).
- Patients with progressive ANLL or ALL following second or third-line treatment regimens.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Health System
Durham, North Carolina, 27710
About this study
Official title: Total Body Irradiation With Fludarabine Conditioning Followed by Transplantation With Combined Umbilical Cord Blood Grafts
Results to date of umbilical cord blood transplantation in adult and fully mature adolescent patients are inferior to what is seen in children, due to a lower stem cell dosage in adults and a more toxic conditioning regimen. This phase 1 protocol will use a potentially less toxic bone marrow conditioning regimen, followed by infusion of a combined umbilical cord blood graft that will provide the patient with a higher stem cell dose than can be given with a single umbilical cord blood infusion. The subjects will be conditioned with a total body irradiation (TBI) 13.5 Gy and fludarabine. Following conditioning, up to two unrelated, partially matched umbilical cord blood grafts will be infused that will provide a minimum nucleated cell dose of 3 x 10e7/kg . The primary objective of this study is to measure the frequency of treatment-related toxicity and engraftment.
Read the detailed description
Results to date of umbilical cord blood transplantation in adult and fully mature adolescent patients are inferior to what is seen in children. There are two reasons for this. First is that the stem cell dose, measured in nucleated cells/kg body weight, is considerably lower due to the size of the recipient. This results in a higher incidence of graft failure, delayed engraftment, and impaired immune reconstitution. Multiple studies have suggested that a nucleated cell dose below 1.5 to 2 x 107/kg results in an unacceptably high risk for graft failure. Only a minority of adult patients will have a suitably matched umbilical cord blood unit that contains more than 1.5 x 107 nucleated cells/kg. The second reason for inferior outcome of umbilical cord blood transplantation in adult patients is that in comparison to children, the conventional myeloablative bone marrow conditioning regimens are more toxic. This phase 1 protocol will use a potentially less toxic bone marrow conditioning regimen, followed by infusion of a combined umbilical cord blood graft that will provide the patient with a higher stem cell dose than can be given with a single umbilical cord blood infusion. The subjects will be conditioned with a TBI 13.5 Gy and fludarabine. Fludarabine pharmacokinetics will be measured and correlated with the kinetics of donor cell engraftment as well frequency of treatment-related toxicity. Following conditioning, up to two unrelated, partially matched umbilical cord blood grafts will be infused that will provide a minimum nucleated cell dose of 3 x 10e7/kg. The primary objective of this study is to measure the frequency of treatment-related toxicity and engraftment.
- Conditions
- Lymphoma, Myeloma, Leukemia, Myelodysplasia, Solid Tumors, Hodgkin's Disease
- Being tested
- Total Body Irradiation with Fludarabine in UCB Transplants
- Keywords
- Umbilical Cord Blood Graft, Stem Cell Transplantation
- Medical subject headings
- Lymphoma, Neoplasms, Plasma Cell, Leukemia, Anemia, Refractory, with Excess of Blasts, Hodgkin Disease, Primary Myelofibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Total Body Irradiation with Fludarabine in UCB TransplantsProcedure or surgery
Administration of the preparative regimen, infusion of the stem cell graft, inpatient care during the immediate post-transplant period and outpatient follow-up for the first 3 months after transplant and at 6, 12, 24 and 36 months. Patients will have human leukocyte antigen (HLA) serologic typing and DNA typing. Bags of UCB are thawed, and diluted by 1:1 volume using a 5% albumin/dextran solution. The thawed and diluted umbilical cord blood unit (UCBU) is next weighed and centrifuged. Specimens are obtained for cell count and viability, culture, clonogenic assays, and phenotype. The UCB is infused at a rate of 1-3 ml/min. Furosemide (0.5-1.0 mg/kg/dose) may be given if volume overload or decreased urine output occurs. Each UCB infusion shall be tested for sterility, CFU content, number of CD34+ cells, cell count and viability.
| Study group | Role | What they receive |
|---|---|---|
| I | Experimental | Total Body Irradiation (TBI)/Flu Conditioning followed by combined UCB Receives: Procedure: Total Body Irradiation with Fludarabine in UCB Transplants |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary objective will be to measure the time to and rate of hematologic engraftment following transplant and the frequency of treatment-related mortality.
Measured: 3 years
Secondary outcomes (2)
The secondary objective will be to estimate the proportion of patients developing acute and chronic graft-versus-host disease, 100 day treatment-related mortality, and to measure disease-free survival.
Measured: 3 years
The tertiary objective will be to measure the time to immunologic reconstitution as defined by normal numbers of T and B cells, normal T-cell proliferative responses, normal natural killer (NK) cell function, and normal immunoglobulin synthesis.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2008 (estimated)
- Study startSep 2005
- Primary completionFeb 2014
- Study completionFeb 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mitchell Horwitz, MD, Principal investigator, Duke Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00606437
- Sponsor's protocol ID
- Pro00009529
- Status last verified
- May 2014
- First submitted
- 7 Jan 2008
- Last updated
- 16 May 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Total Body Irradiation With Fludarabine Conditioning Followed by Transplantation With Combined Umbilical Cord Blood Grafts
- ClinicalTrials.gov ID
- NCT00606437
- Acronym / sponsor ID
- Pro00009529
- Conditions
- Lymphoma, Myeloma, Leukemia, Myelodysplasia, Solid Tumors, Hodgkin's Disease
- Keywords
- Umbilical Cord Blood Graft, Stem Cell Transplantation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Study start
- Sep 2005
- Primary completion
- Feb 2014 (actual)
- Study completion
- Feb 2014 (actual)
- First posted
- 4 Feb 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Results to date of umbilical cord blood transplantation in adult and fully mature adolescent patients are inferior to what is seen in children, due to a lower stem cell dosage in adults and a more toxic conditioning regimen. This phase 1 protocol will use a potentially less toxic bone marrow conditioning regimen, followed by infusion of a combined umbilical cord blood graft that will provide the patient with a higher stem cell dose than can be given with a single umbilical cord blood infusion. The subjects will be conditioned with a total body irradiation (TBI) 13.5 Gy and fludarabine. Following conditioning, up to two unrelated, partially matched umbilical cord blood grafts will be infused that will provide a minimum nucleated cell dose of 3 x 10e7/kg . The primary objective of this study is to measure the frequency of treatment-related toxicity and engraftment.
Detailed description
Results to date of umbilical cord blood transplantation in adult and fully mature adolescent patients are inferior to what is seen in children. There are two reasons for this. First is that the stem cell dose, measured in nucleated cells/kg body weight, is considerably lower due to the size of the recipient. This results in a higher incidence of graft failure, delayed engraftment, and impaired immune reconstitution. Multiple studies have suggested that a nucleated cell dose below 1.5 to 2 x 107/kg results in an unacceptably high risk for graft failure. Only a minority of adult patients will have a suitably matched umbilical cord blood unit that contains more than 1.5 x 107 nucleated cells/kg. The second reason for inferior outcome of umbilical cord blood transplantation in adult patients is that in comparison to children, the conventional myeloablative bone marrow conditioning regimens are more toxic. This phase 1 protocol will use a potentially less toxic bone marrow conditioning regimen, followed by infusion of a combined umbilical cord blood graft that will provide the patient with a higher stem cell dose than can be given with a single umbilical cord blood infusion. The subjects will be conditioned with a TBI 13.5 Gy and fludarabine. Fludarabine pharmacokinetics will be measured and correlated with the kinetics of donor cell engraftment as well frequency of treatment-related toxicity. Following conditioning, up to two unrelated, partially matched umbilical cord blood grafts will be infused that will provide a minimum nucleated cell dose of 3 x 10e7/kg. The primary objective of this study is to measure the frequency of treatment-related toxicity and engraftment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| I | Experimental | Procedure: Total Body Irradiation with Fludarabine in UCB TransplantsTotal Body Irradiation (TBI)/Flu Conditioning followed by combined UCB |
Who may qualify
- Ages
- 14 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (25 listed)
- Age 14 to 65 years.
- Available cord blood graft.
- Patients with high risk ALL in first complete remission, with high risk being defined by the presence of t(4;11), t(9;22) or t(1;19) or patients presenting with extreme hyperleukocytosis (WBC > 500,000/ul) or partial remission after induction therapy.
- Adult patients with acute non-lymphocytic leukemia (ANLL) in first complete remission with high-risk cytogenetics (monosomy chromosome 5 or 7, del (5q), abn (3q26), complex karyotypic abnormalities) or failure to achieve complete remission after standard induction therapy.
- All patients with ALL or ANLL in second or subsequent remission or partial remission.
Key exclusion criteria (2 listed)
- Patients that have circulating antibodies specific for donor major histocompatibility antigens (as determined by panel of reactive antibody assay).
- Patients with progressive ANLL or ALL following second or third-line treatment regimens.
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 |
|---|---|---|
| Total Body Irradiation with Fludarabine in UCB TransplantsAdministration of the preparative regimen, infusion of the stem cell graft, inpatient care during the immediate post-transplant period and outpatient follow-up for the first 3 months after transplant and at 6, 12, 24 and 36 months. Patients will have human leukocyte antigen (HLA) serologic typing and DNA typing. Bags of UCB are thawed, and diluted by 1:1 volume using a 5% albumin/dextran solution. The thawed and diluted umbilical cord blood unit (UCBU) is next weighed and centrifuged. Specimens are obtained for cell count and viability, culture, clonogenic assays, and phenotype. The UCB is infused at a rate of 1-3 ml/min. Furosemide (0.5-1.0 mg/kg/dose) may be given if volume overload or decreased urine output occurs. Each UCB infusion shall be tested for sterility, CFU content, number of CD34+ cells, cell count and viability. | Procedure or surgery | I |
Primary outcome
The primary objective will be to measure the time to and rate of hematologic engraftment following transplant and the frequency of treatment-related mortality.
Time frame: 3 years
2 secondary outcomes
The secondary objective will be to estimate the proportion of patients developing acute and chronic graft-versus-host disease, 100 day treatment-related mortality, and to measure disease-free survival.
Time frame: 3 years
The tertiary objective will be to measure the time to immunologic reconstitution as defined by normal numbers of T and B cells, normal T-cell proliferative responses, normal natural killer (NK) cell function, and normal immunoglobulin synthesis.
Time frame: 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2014.
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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.
Mitchell Horwitz, MD principal investigator
Duke Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Total Body Irradiation with Fludarabine in UCB Transplants in people with Lymphoma and Myeloma, run by Duke University 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 25 inclusion and 2 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: finished, as of the sponsor's last update on 16 May 2014. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
The primary objective will be to measure the time to and rate of hematologic engraftment following transplant and the frequency of treatment-related mortality. (time frame: 3 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 16 May 2014.