Hematologic MalignancyPhase 1/2NCT00673114
Unrelated Cord Blood Transplant Plus a Haplo-Identical (Half-Matched), T-Cell Depleted Stem Transplant From a Related Donor for Subjects With High Risk Malignancies
A Phase 1/2 study testing haplo/cord transplant in people with Hematologic Malignancy and Myelodysplastic Syndrome (MDS), run by Joanne Kurtzberg, MD at 1 site in United States.
Trial summary
Subjects will be diagnosed with a hematological malignancy (cancer of the blood), which is unlikely to be cured with conventional non-transplant therapy. The best results of bone marrow transplant are obtained with the donor is a relative that has identical tissue type (HLA-type). Read more about this study
- Who is it for?
- Ages Up to 55 years
- Conditions the study is for
- Hematologic Malignancy, Myelodysplastic Syndrome (MDS), Aplastic Anemia
- What is being tested?
- haplo/cord transplant
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2007to Apr 2012
- Phase
- Phase 1/2
- 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 Up to 55 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patient Selection Criteria: Patients with high risk or refractory malignancies, myelodysplasia (MDS) or severe aplastic anemia amenable to stem cell transplantation therapy but lacking conventional related or unrelated donors will be eligible for this trial.
- Have a consenting related haplo-identical (3/6 or 4/6) stem cell donor;
- Have an available 3, 4, 5, or 6/6 antigen matching unrelated UCB unit that will deliver a cell dose between 2.0-5.0 x 10e7cells/kg.
- Not have a consenting 6/6 or 5/6 antigen matched related bone marrow donor or genetically matched unrelated BM or adult stem cell donor.
- Patients must be <55 years of age at the time of study enrollment.
- Patients must have histologically confirmed diagnosis of a hematologic malignancy, MDS or severe aplastic anemia. Eligible patients include the following:
Show all 27Show fewer
- Patients with high risk ALL in first complete remission, with high risk being defined by the presence of hypodiploidy, t(4;11; MLL. 11q23) or t(9;22), or patients presenting with extreme hyperleukocytosis (initial WBC >500,000/ml) or failure to achieve a complete remission after standard induction therapy.
- All patients with ALL or ANLL in second or subsequent remission.
- Patients with ALL or ANLL in relapse.
- Patients with MDS.
- Patients with CML in any chronic phase, accelerated phase or blast crisis.
- Patients with severe aplastic anemia refractory to medical therapy.
- Patients must not have active CNS disease at the time of study enrollment.
- Patients must have a good performance status (Lansky 80-100%, Karnofsky 50-100%).
- Patients must have adequate function of other organ systems as measured by:
- Creatinine < 2.0 mg/dl and creatinine clearance > 50 cc/min/m2.
- Hepatic transaminases (ALT/AST) < 4 x normal, bilirubin < 2.0 mg/dl.
- Normal cardiac function by echocardiogram or radionuclide scan, (ejection fraction or shortening fraction > 80% of normal value for age).
- Pulmonary function tests demonstrating FVC and FEV1 of >60% of predicted for age. For adult patients DLCO > 60% of predicted. If patient cannot perform PFTs, clearance by the pediatric or adult pulmonologist will be required.
- Patients must not have uncontrolled infections at the time of cytoreduction.
- Patient, parent, or legal guardian must have given written informed consent according to FDA guidelines.
- Patients may not be pregnant or lactating and must have a current negative pregnancy test.
- Patients must have a minimum life expectancy of at least 3 months.
- Patients must have an available related haplo-identical stem cell donor and an available unrelated cord blood donor delivering between 2 x10e7 cells/kg and 5 x 10e7 cells/kg and matching at a minimum of 3/6 HLA loci.
- Patients must be HIV negative.
- Patients must not be concurrently involved in any other clinical trial that affects engraftment or immune reconstitution (e.g. other hematopoietic growth factors).
- Patients must not have any co-morbid condition which, in the view of the Principal Investigators, renders the patient at too high a risk from treatment complications and regimen related morbidity/mortality.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center Pediatric Blood and Marrow Transplant
Durham, North Carolina, 27705
About this study
Official title: A Prospective, Phase I/II Trial Determining the Efficacy and Safety of Allogeneic Hematopoietic Stem Cell Transplantation Using Banked Unrelated Umbilical Cord Blood Supplemented With Related, Haplo-Identical T-Cell Depleted Stem Cells in Subjects With High Risk Malignancies
Subjects will be diagnosed with a hematological malignancy (cancer of the blood), which is unlikely to be cured with conventional non-transplant therapy. The best results of bone marrow transplant are obtained with the donor is a relative that has identical tissue type (HLA-type). These subjects will not have such a donor available but they will have a appropriately matching unrelated umbilical cord blood unit (UCB). However, the cord blood unit does not contain a high enough number of cells and may take longer to engraft (or grow). The purpose of this study is to determine whether the addition of stem cells from a family member to supplement a standard unrelated cord blood transplant is safe and will increase the success of the cord blood transplantation procedure. Subjects enrolled in this study will receive an unrelated cord blood transplant plus a haplo-identical (half-matched), T-cell depleted stem transplant from a related donor. The goal of this study is to determine whether the addition of the related stem cells accelerates bone marrow recovery and improves long-term disease free survival.
Read the detailed description
Over the past decade, umbilical cord blood transplantation has been shown to be a viable alternative donor stem cell source for hematopoietic cell transplantation in subjects with catastrophic diseases treatable with transplantation therapy. UCB cells can cross partially mismatched HLA barriers without intolerable acute or chronic Graft-versus-Host Disease(GVHD). Thus, many subjects lacking a sufficiently matched, living related or unrelated bone marrow or adult stem cell donor, can use partially HLA-matched UCB cells for stem cell rescue after myeloablative irradiation and/or chemotherapy. UCB Cell dose, expressed per kilogram of recipient body weight, is the best predictor of outcomes after UCB transplantation. Cell dose thresholds strongly correlating with outcomes have been identified.
In subjects receiving lower cell doses, while durable engraftment will ultimately occur, there are significant delays in myeloid and platelet engraftment which, at best, result in longer hospitalization and significant increases in resource utilization and in the worst cases, result in increased early deaths from infection and regimen-related toxicity.
In infants and children weighing <40kg, it is possible to find a sufficiently matched UCB unit that will deliver a dose of cells critical for successful engraftment (defined as 5 x 10^7 nucleated cells/kg) within a reasonable time frame in >90% of subjects. In teenagers and adults weighing >40kg, this is not always possible. Because UCB units contain a relatively fixed number of total nucleated cells, units delivering optimal cell dosing for subjects weighing >70kg will only be identified <10% of the time. Attempts to increase the dose of cells available for UCBT have included ex vivo expansion and combined unit transplantation. While expansion of UCB cells ex vivo is possible, infusion of these expanded cells have not resulted in shortening of engraftment times. Likewise, combinations of up to 5 UCB units for a single myeloablative transplant have not shortened time to neutrophil or platelet engraftment.
In this study, we take an alternative approach to facilitating early myeloid engraftment in subjects undergoing UCB transplantation therapy. In subjects who cannot only identify a donor delivering a cell dose >2 x 10^7 nucleated cells/kg, we will augment the UCBT with a lower dose of haplo-identical, T-cell depleted stem cells from a related adult donor to facilitate early, short-term engraftment with the primary goal of minimizing early infections and other non-relapse mortality while the UCB cells engraft as the durable and permanent graft. As the immunocompetent UCB cells engraft, we expect that they will reject the immunologically incompetent haplo-identical adult stem cells. Thus, after approximately 100-180 days post transplant, the subject should convert to 100% donor chimerism with the UCB donor graft.
In this study, we will investigate the use of unrelated UCB obtained from the umbilical cord blood banks supplements with related, haplo-identical, T-cell depleted stem cells in subjects with high risk refractory malignancies, myelodysplasia or severe aplastic anemia amenable to stem cell transplantation therapy but lacking conventional related or unrelated donors.
OBJECTIVES:
- To determine the safety of co-transplantation of unrelated umbilical cord blood supplemented with related, haplo-identical, T-cell depleted stem cells in subjects with high risk malignancies.
- To describe the rates of neutrophil and platelet engraftment and immune reconstitution in these subjects.
- To determine whether short and long term lymphohematopoietic engraftment is derived from one or both donor sources.
The primary endpoint of the study is number of days to ANC of 500/uL
The secondary endpoints of the study are:
- 180 day survival
- Non-relapse mortality in the first 180 days post transplant
- Number of days to untransfused platelet count of 50K/uL
- Incidence of primary and secondary graft failure
- Incidence and severity of acute and chronic graft-versus-host disease (GVHD)
- Pace and quality of immune reconstitution
- Rates of leukemic relapse
- Donor chimerism
- Being tested
- haplo/cord transplant
- Keywords
- Haplo/cord, hematologic malignancy, MDS, Aplastic Anemia, AML, ALL, CML
- Medical subject headings
- Hematologic Neoplasms, Myelodysplastic Syndromes, Anemia, Aplastic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
haplo/cord transplantBiological
T-cell depleted haplo-matched cells from related donor and unrelated umbilical cord blood
| Study group | Role | What they receive |
|---|---|---|
| Transplant Recipients | Other | Not described Receives: Biological: haplo/cord transplant |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Number of Participants Reaching Primary Endpoint of Absolute Neutrophil Count (ANC) of 500/uL (Engraftment).
Measured: By day 100
Secondary outcomes (7)
180 Day Survival
Number of participants alive at 180 days post transplant
Measured: 180 days
Non-Relapse Mortality at 180 Days Post Transplant
Measured: 180 days
Platelet Engraftment (Untransfused and Platelet Count > 50,000)
Participants platelet engrafted.
Measured: Approximately 1 year
Incidence of Primary and Secondary Graft Failure
Number of participants experiencing graft failure.
Measured: 100 days post transplant
Number of Participants With Acute or Chronic Graft-versus-host Disease (GVHD)
Acute and chronic GVHD
Measured: two years
Rates of Leukemic Relapse
Number of participants relapsed
Measured: Up to 2 years post transplant
Number of Participants With Donor Cells at 100 Days Post-transplant
Measured: Post transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2008 (estimated)
- Study startAug 2007
- Primary completionApr 2012
- Study completionApr 2012
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 Hematologic MalignancyStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Joanne Kurtzberg, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Miltenyi Biomedicine GmbH
- Responsible party
- Sponsor-investigator, Joanne Kurtzberg, MD, Duke University
- Investigators
- Joanne Kurtzberg, MD, Principal investigator, Duke University Medical Center Pediatric Blood and Marrow Transplant
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00673114
- Sponsor's protocol ID
- Pro00008292
- Other IDs
- 8717
- Status last verified
- Mar 2015
- First submitted
- 27 Dec 2007
- Last updated
- 3 Apr 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Phase I/II Trial Determining the Efficacy and Safety of Allogeneic Hematopoietic Stem Cell Transplantation Using Banked Unrelated Umbilical Cord Blood Supplemented With Related, Haplo-Identical T-Cell Depleted Stem Cells in Subjects With High Risk Malignancies
- ClinicalTrials.gov ID
- NCT00673114
- Acronym / sponsor ID
- Pro00008292
- Keywords
- Haplo/cord, hematologic malignancy, MDS, Aplastic Anemia, AML, ALL, CML
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Joanne Kurtzberg, MDUniversity, hospital or other
- Collaborators
- Miltenyi Biomedicine GmbH
- Study start
- Aug 2007
- Primary completion
- Apr 2012 (actual)
- Study completion
- Apr 2012 (actual)
- First posted
- 7 May 2008 (estimated)
- Results
- Posted 24 Dec 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Subjects will be diagnosed with a hematological malignancy (cancer of the blood), which is unlikely to be cured with conventional non-transplant therapy. The best results of bone marrow transplant are obtained with the donor is a relative that has identical tissue type (HLA-type). These subjects will not have such a donor available but they will have a appropriately matching unrelated umbilical cord blood unit (UCB). However, the cord blood unit does not contain a high enough number of cells and may take longer to engraft (or grow). The purpose of this study is to determine whether the addition of stem cells from a family member to supplement a standard unrelated cord blood transplant is safe and will increase the success of the cord blood transplantation procedure. Subjects enrolled in this study will receive an unrelated cord blood transplant plus a haplo-identical (half-matched), T-cell depleted stem transplant from a related donor. The goal of this study is to determine whether the addition of the related stem cells accelerates bone marrow recovery and improves long-term disease free survival.
Detailed description
Over the past decade, umbilical cord blood transplantation has been shown to be a viable alternative donor stem cell source for hematopoietic cell transplantation in subjects with catastrophic diseases treatable with transplantation therapy. UCB cells can cross partially mismatched HLA barriers without intolerable acute or chronic Graft-versus-Host Disease(GVHD). Thus, many subjects lacking a sufficiently matched, living related or unrelated bone marrow or adult stem cell donor, can use partially HLA-matched UCB cells for stem cell rescue after myeloablative irradiation and/or chemotherapy. UCB Cell dose, expressed per kilogram of recipient body weight, is the best predictor of outcomes after UCB transplantation. Cell dose thresholds strongly correlating with outcomes have been identified.
In subjects receiving lower cell doses, while durable engraftment will ultimately occur, there are significant delays in myeloid and platelet engraftment which, at best, result in longer hospitalization and significant increases in resource utilization and in the worst cases, result in increased early deaths from infection and regimen-related toxicity.
In infants and children weighing <40kg, it is possible to find a sufficiently matched UCB unit that will deliver a dose of cells critical for successful engraftment (defined as 5 x 10^7 nucleated cells/kg) within a reasonable time frame in >90% of subjects. In teenagers and adults weighing >40kg, this is not always possible. Because UCB units contain a relatively fixed number of total nucleated cells, units delivering optimal cell dosing for subjects weighing >70kg will only be identified <10% of the time. Attempts to increase the dose of cells available for UCBT have included ex vivo expansion and combined unit transplantation. While expansion of UCB cells ex vivo is possible, infusion of these expanded cells have not resulted in shortening of engraftment times. Likewise, combinations of up to 5 UCB units for a single myeloablative transplant have not shortened time to neutrophil or platelet engraftment.
In this study, we take an alternative approach to facilitating early myeloid engraftment in subjects undergoing UCB transplantation therapy. In subjects who cannot only identify a donor delivering a cell dose >2 x 10^7 nucleated cells/kg, we will augment the UCBT with a lower dose of haplo-identical, T-cell depleted stem cells from a related adult donor to facilitate early, short-term engraftment with the primary goal of minimizing early infections and other non-relapse mortality while the UCB cells engraft as the durable and permanent graft. As the immunocompetent UCB cells engraft, we expect that they will reject the immunologically incompetent haplo-identical adult stem cells. Thus, after approximately 100-180 days post transplant, the subject should convert to 100% donor chimerism with the UCB donor graft.
In this study, we will investigate the use of unrelated UCB obtained from the umbilical cord blood banks supplements with related, haplo-identical, T-cell depleted stem cells in subjects with high risk refractory malignancies, myelodysplasia or severe aplastic anemia amenable to stem cell transplantation therapy but lacking conventional related or unrelated donors.
OBJECTIVES:
- To determine the safety of co-transplantation of unrelated umbilical cord blood supplemented with related, haplo-identical, T-cell depleted stem cells in subjects with high risk malignancies.
- To describe the rates of neutrophil and platelet engraftment and immune reconstitution in these subjects.
- To determine whether short and long term lymphohematopoietic engraftment is derived from one or both donor sources.
The primary endpoint of the study is number of days to ANC of 500/uL
The secondary endpoints of the study are:
- 180 day survival
- Non-relapse mortality in the first 180 days post transplant
- Number of days to untransfused platelet count of 50K/uL
- Incidence of primary and secondary graft failure
- Incidence and severity of acute and chronic graft-versus-host disease (GVHD)
- Pace and quality of immune reconstitution
- Rates of leukemic relapse
- Donor chimerism
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Transplant Recipients | Other | Biological: haplo/cord transplant |
Who may qualify
- Ages
- Up to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (27 listed)
- Patient Selection Criteria: Patients with high risk or refractory malignancies, myelodysplasia (MDS) or severe aplastic anemia amenable to stem cell transplantation therapy but lacking conventional related or unrelated donors will be eligible for this trial.
- Have a consenting related haplo-identical (3/6 or 4/6) stem cell donor;
- Have an available 3, 4, 5, or 6/6 antigen matching unrelated UCB unit that will deliver a cell dose between 2.0-5.0 x 10e7cells/kg.
- Not have a consenting 6/6 or 5/6 antigen matched related bone marrow donor or genetically matched unrelated BM or adult stem cell donor.
- Patients must be <55 years of age at the time of study enrollment.
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| haplo/cord transplantT-cell depleted haplo-matched cells from related donor and unrelated umbilical cord blood | Biological | Transplant Recipients |
Primary outcome
The Number of Participants Reaching Primary Endpoint of Absolute Neutrophil Count (ANC) of 500/uL (Engraftment).
Time frame: By day 100
7 secondary outcomes
180 Day Survival
Time frame: 180 days
Non-Relapse Mortality at 180 Days Post Transplant
Time frame: 180 days
Platelet Engraftment (Untransfused and Platelet Count > 50,000)
Time frame: Approximately 1 year
Incidence of Primary and Secondary Graft Failure
Time frame: 100 days post transplant
Number of Participants With Acute or Chronic Graft-versus-host Disease (GVHD)
Time frame: two years
Rates of Leukemic Relapse
Time frame: Up to 2 years post transplant
Number of Participants With Donor Cells at 100 Days Post-transplant
Time frame: Post transplant
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2015.
- 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.
Joanne Kurtzberg, MD principal investigator
Duke University Medical Center Pediatric Blood and Marrow Transplant
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing haplo/cord transplant in people with Hematologic Malignancy and Myelodysplastic Syndrome (MDS), run by Joanne Kurtzberg, MD 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 27 inclusion and 0 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 3 Apr 2015. 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 combined 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.
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 24 Dec 2013). 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?
The Number of Participants Reaching Primary Endpoint of Absolute Neutrophil Count (ANC) of 500/uL (Engraftment). (time frame: By day 100). 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 3 Apr 2015.