LeukemiaPhase 2NCT00143559
Stem Cell Transplantation as Immunotherapy for Hematologic Malignancies
A Phase 2 study testing Systematic chemotherapy and antibodies, Allogeneic stem cell transplantation and Miltenyi CliniMACS in people with Leukemia and Acute Lymphoblastic Leukemia, run by St. Jude Children's Research Hospital at 1 site in United States.
Trial summary
Blood and marrow stem cell transplant has improved the outcome for patients with high-risk hematologic malignancies. However, most patients do not have an appropriate HLA (immune type) matched sibling donor available and/or are unable to identify an acceptable unrelated HLA matched donor through the registries in a… Read more about this study
- Who is it for?
- Ages 2 to 21 years
- Conditions the study is for
- Leukemia, Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia
- What is being tested?
- Systematic chemotherapy and antibodies, Allogeneic stem cell transplantation and Miltenyi CliniMACS
- Type of treatment
- Injection or infusion, Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2005to Jan 2009
- Phase
- Phase 2
- 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 2 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Eligible participants were assigned to one of two different strata dependent on diagnosis, disease status and/or past transplant experience. Both strata received the same intervention but will be followed and analyzed separately.
- Group A must have one of the following diagnosis
- Acute lymphoid leukemia (ALL) in second or subsequent remission or high risk in first remission
- Acute myeloid leukemia (AML) in remission or with ≤ 25% blasts in bone marrow
- Chronic myeloid leukemia (CML)
- Juvenile myelomonocytic leukemia (JMML)
Show all 25Show fewer
- Myelodysplastic syndrome (MDS)
- Paroxysmal nocturnal hemoglobinuria (PNH)
- Hodgkin's (HD) or non-Hodgkin's lymphoma (NHL) in second or subsequent remission after autologous HSCT, or unable to have hematopoietic stem cells collected for autologous HSCT
- Group B must have one of the following refractory diagnosis (chemoresistant relapse or primary induction failure)
- Acute lymphoid leukemia (ALL)
- Acute myeloid leukemia (AML) ≥ 25% blast in bone marrow
- Secondary AML / MDS
- Chronic myeloid leukemia (CML) in accelerated phase or blast crisis
- Juvenile myelomonocytic leukemia (JMML)
- Myelodysplastic syndrome (MDS)
- Hodgkin's (HD) or non-Hodgkin's lymphoma (NHL) with residual disease followed by autologous HSCT or who have chemo-resistant disease
- Or patients who have undergone prior allogeneic HSCT or who have a co-morbid condition that in the medical opinion of the Transplant Faculty makes standard myeloablation prohibited
- At least 2 and less than or equal to 21 years of age
- Lacks suitable HLA-identical sibling or matched available unrelated donor and has a mismatched family member donor that is available, HIV negative and at least 18 years old
- Cardiac shortening fraction ≥ 25%
- Creatinine clearance ≥ 40 cc/min/1.73m^2
- FVC ≥ 40% of predicted or pulse oximetry ≥ 92% on room air
- Direct bilirubin ≤ 3 mg/dL or SGPT ≤ 500 U/L
- Karnofsky or Lansky (age dependent) performance score of ≥ 50
Who cannot join
- Known allergy to murine products
- Lactating (female patient)
- Pregnancy (female patient)
- Active central nervous system (CNS) leukemia
Trial locations and contacts
1 site in 1 country.
United States1 site
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
About this study
Official title: Haploidentical Hematopoietic Stem Cell Transplantation Utilizing Partial T-Cell Depletion as Immunotherapy for Hematologic Malignancies
Blood and marrow stem cell transplant has improved the outcome for patients with high-risk hematologic malignancies. However, most patients do not have an appropriate HLA (immune type) matched sibling donor available and/or are unable to identify an acceptable unrelated HLA matched donor through the registries in a timely manner. Another option is haploidentical transplant using a partially matched family member donor.
Although haploidentical transplant has proven curative in many patients, this procedure has been hindered by significant complications, primarily regimen-related toxicity including GVHD and infection due to delayed immune reconstitution. These can, in part, be due to certain white blood cells in the graft called T cells. GVHD happens when the donor T cells recognize the body tissues of the patient (the host) are different and attack these cells. Although too many T cells increase the possibility of GVHD, too few may cause the recipient's immune system to reconstitute slowly or the graft to fail to grow, leaving the patient at high-risk for significant infection.
Read more
For these reasons, a primary focus for researchers is to engineer the graft to provide a T cell dose that will reduce the risk for GVHD, yet provide a sufficient number of cells to facilitate immune reconstitution and graft integrity. Building on prior institutional trials, this study will provide patients with a haploidentical graft engineered to specific T cell target values using the CliniMACS system. A reduced intensity, preparative regimen will be used in an effort to reduce regimen-related toxicity and mortality.
Two groups of patients were enrolled on this study. One group included those with high-risk hematologic malignancies and the second group included participants with refractory hematologic malignancies or undergoing a second transplant. The primary aim of the study was to estimate the relapse rate in the one group of research participants with refractory hematologic malignancies or those undergoing second allogeneic transplant. Both groups will be followed and analyzed separately in regards to the secondary objectives.
This study was closed to accrual on April 2006 as it met the specific safety stopping rules regarding occurrence of severe graft vs. host disease. Although this study is no longer open to accrual, the treated participants continue to be followed as directed by the protocol.
Read the detailed description
Secondary outcome evaluations for this clinical study included the following:
- To estimate one-year overall survival for research participants with high risk malignancies who receive a haploidentical HSCT
- To compare overall survival and cumulative incidence of relapse for the two groups of patients with their corresponding historical controls
- To estimate disease-free survival and event-free survival in participants with hematologic malignancies who receive a haploidentical HSCT
- To estimate the incidence of overall grade 3-4 acute GvHD in research participants with hematologic malignancies who receive a haploidentical HSCT
- To estimate the incidence of chronic GvHD and graft failure in research participants with hematologic malignancies who receive a haploidentical HSCT
- To estimate the incidence of non-hematologic regimen-related toxicity and regimen-related mortality in the first 100 days post-transplant in research participants with hematologic malignancies who receive a haploidentical HSCT
- To estimate the number of research participants who develop evidence of EBV reactivation or post-transplant lymphoproliferative disease (PTLPD)
- To describe disease-free survival, GvHD and engraftment in research participants receiving grafts from Killer immunoglobulin-like receptor (KIR) mismatched and KIR matched haploidentical donors
- Conditions
- Leukemia, Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Chronic Myeloid Leukemia, Juvenile Myelomonocytic Leukemia, Myelodysplastic Syndrome
- Being tested
- Systematic chemotherapy and antibodies, Allogeneic stem cell transplantation, Miltenyi CliniMACS
- Keywords
- Allogeneic stem cell transplantation, Haploidentical stem cell transplant, Mismatched family member stem cell donor transplant, Bone marrow transplant, High risk hematological malignancies, T-cell depletion methodology, Miltenyi Biotec CliniMACS stem cell selection device
- Medical subject headings
- Leukemia, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia, Myelomonocytic, Juvenile, Myelodysplastic Syndromes, Hemoglobinuria, Paroxysmal, Hodgkin Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Systematic chemotherapy and antibodiesDrug
Systemic chemotherapy and antibodies as follows:
Transplant recipients received a reduced intensity conditioning regimen consisting of OKT-3, fludarabine, thiotepa, and melphalan followed by an infusion of a T-cell depleted haploidentical hematopoietic stem cell graft. The antibody Rituximab was administered within 24 hours of the infusion in an effort to prevent PTLPD. In addition to T -cell depletion of the donor product, Mycophenylate mofetil was provided over several months as prophylaxis for GVHD
Allogeneic stem cell transplantationProcedure or surgery
An infusion of HLA mismatched family member donor stem cells processed through the use of the investigational Miltenyi Biotec CliniMACS device
Miltenyi CliniMACSDevice
Also called Haploidentical donor stem cell transplant, Mismatched family member transplant, Allogeneic stem cell transplant, Reduced intensity conditioning regimen
Miltenyi Biotec CliniMACS stem cell selection device
| Study group | Role | What they receive |
|---|---|---|
| 1 | Other | Not described Receives: Drug: Systematic chemotherapy and antibodies; Procedure: Allogeneic stem cell transplantation; Device: Miltenyi CliniMACS |
What is being measured
The primary outcome is the main question the study is designed to answer.
To measure the rate of disease relapse by six months posttransplant in children and young adults with refractory hematologic malignancies who receive a haploidentical stem cell graft processed using the investigational CliniMACS cell sorting device.
Measured: September 2006
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Sep 2005 (estimated)
- Study startAug 2005
- Primary completionJul 2006
- Study completionJan 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by St. Jude Children's Research HospitalThe 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Jude Children's Research Hospital
- Sponsor type
- University, hospital or other
- Investigators
- Gregory Hale, M.D., Principal investigator, St. Jude Children's Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00143559
- Sponsor's protocol ID
- HAPREF
- Status last verified
- Jan 2009
- First submitted
- 1 Sep 2005
- Last updated
- 29 Jan 2009
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 29 Jan 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Haploidentical Hematopoietic Stem Cell Transplantation Utilizing Partial T-Cell Depletion as Immunotherapy for Hematologic Malignancies
- ClinicalTrials.gov ID
- NCT00143559
- Acronym / sponsor ID
- HAPREF
- Conditions
- Leukemia, Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Chronic Myeloid Leukemia, Juvenile Myelomonocytic Leukemia, Myelodysplastic Syndrome
- Keywords
- Allogeneic stem cell transplantation, Haploidentical stem cell transplant, Mismatched family member stem cell donor transplant, Bone marrow transplant, High risk hematological malignancies, T-cell depletion methodology, Miltenyi Biotec CliniMACS stem cell selection device
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- St. Jude Children's Research HospitalUniversity, hospital or other
- Study start
- Aug 2005
- Primary completion
- Jul 2006 (actual)
- Study completion
- Jan 2009 (actual)
- First posted
- 2 Sep 2005 (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.
Blood and marrow stem cell transplant has improved the outcome for patients with high-risk hematologic malignancies. However, most patients do not have an appropriate HLA (immune type) matched sibling donor available and/or are unable to identify an acceptable unrelated HLA matched donor through the registries in a timely manner. Another option is haploidentical transplant using a partially matched family member donor.
Although haploidentical transplant has proven curative in many patients, this procedure has been hindered by significant complications, primarily regimen-related toxicity including GVHD and infection due to delayed immune reconstitution. These can, in part, be due to certain white blood cells in the graft called T cells. GVHD happens when the donor T cells recognize the body tissues of the patient (the host) are different and attack these cells. Although too many T cells increase the possibility of GVHD, too few may cause the recipient's immune system to reconstitute slowly or the graft to fail to grow, leaving the patient at high-risk for significant infection.
For these reasons, a primary focus for researchers is to engineer the graft to provide a T cell dose that will reduce the risk for GVHD, yet provide a sufficient number of cells to facilitate immune reconstitution and graft integrity. Building on prior institutional trials, this study will provide patients with a haploidentical graft engineered to specific T cell target values using the CliniMACS system. A reduced intensity, preparative regimen will be used in an effort to reduce regimen-related toxicity and mortality.
Two groups of patients were enrolled on this study. One group included those with high-risk hematologic malignancies and the second group included participants with refractory hematologic malignancies or undergoing a second transplant. The primary aim of the study was to estimate the relapse rate in the one group of research participants with refractory hematologic malignancies or those undergoing second allogeneic transplant. Both groups will be followed and analyzed separately in regards to the secondary objectives.
This study was closed to accrual on April 2006 as it met the specific safety stopping rules regarding occurrence of severe graft vs. host disease. Although this study is no longer open to accrual, the treated participants continue to be followed as directed by the protocol.
Detailed description
Secondary outcome evaluations for this clinical study included the following:
- To estimate one-year overall survival for research participants with high risk malignancies who receive a haploidentical HSCT
- To compare overall survival and cumulative incidence of relapse for the two groups of patients with their corresponding historical controls
- To estimate disease-free survival and event-free survival in participants with hematologic malignancies who receive a haploidentical HSCT
- To estimate the incidence of overall grade 3-4 acute GvHD in research participants with hematologic malignancies who receive a haploidentical HSCT
- To estimate the incidence of chronic GvHD and graft failure in research participants with hematologic malignancies who receive a haploidentical HSCT
- To estimate the incidence of non-hematologic regimen-related toxicity and regimen-related mortality in the first 100 days post-transplant in research participants with hematologic malignancies who receive a haploidentical HSCT
- To estimate the number of research participants who develop evidence of EBV reactivation or post-transplant lymphoproliferative disease (PTLPD)
- To describe disease-free survival, GvHD and engraftment in research participants receiving grafts from Killer immunoglobulin-like receptor (KIR) mismatched and KIR matched haploidentical donors
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Other | Drug: Systematic chemotherapy and antibodies, Procedure: Allogeneic stem cell transplantation, Device: Miltenyi CliniMACS |
Who may qualify
- Ages
- 2 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (25 listed)
- Eligible participants were assigned to one of two different strata dependent on diagnosis, disease status and/or past transplant experience. Both strata received the same intervention but will be followed and analyzed separately.
- Group A must have one of the following diagnosis
- Group B must have one of the following refractory diagnosis (chemoresistant relapse or primary induction failure)
- At least 2 and less than or equal to 21 years of age
- Lacks suitable HLA-identical sibling or matched available unrelated donor and has a mismatched family member donor that is available, HIV negative and at least 18 years old
Key exclusion criteria (4 listed)
- Known allergy to murine products
- Lactating (female patient)
- Pregnancy (female patient)
- Active central nervous system (CNS) leukemia
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 |
|---|---|---|
| Systematic chemotherapy and antibodiesSystemic chemotherapy and antibodies as follows: Transplant recipients received a reduced intensity conditioning regimen consisting of OKT-3, fludarabine, thiotepa, and melphalan followed by an infusion of a T-cell depleted haploidentical hematopoietic stem cell graft. The antibody Rituximab was administered within 24 hours of the infusion in an effort to prevent PTLPD. In addition to T -cell depletion of the donor product, Mycophenylate mofetil was provided over several months as prophylaxis for GVHD | Drug | 1 |
| Allogeneic stem cell transplantationAn infusion of HLA mismatched family member donor stem cells processed through the use of the investigational Miltenyi Biotec CliniMACS device | Procedure or surgery | 1 |
| Miltenyi CliniMACSAlso: Haploidentical donor stem cell transplant, Mismatched family member transplant, Allogeneic stem cell transplant, Reduced intensity conditioning regimenMiltenyi Biotec CliniMACS stem cell selection device | Device | 1 |
Primary outcome
To measure the rate of disease relapse by six months posttransplant in children and young adults with refractory hematologic malignancies who receive a haploidentical stem cell graft processed using the investigational CliniMACS cell sorting device.
Time frame: September 2006
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 29 Jan 2009.
- St. Jude Children's Research HospitalLink provided by the sponsor.
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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.
Gregory Hale, M.D. principal investigator
St. Jude Children's Research Hospital
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 Systematic chemotherapy and antibodies, Allogeneic stem cell transplantation and Miltenyi CliniMACS in people with Leukemia and Acute Lymphoblastic Leukemia, run by St. Jude Children's Research Hospital 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 4 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 29 Jan 2009. 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?
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?
To measure the rate of disease relapse by six months posttransplant in children and young adults with refractory hematologic malignancies who receive a haploidentical stem cell graft processed using the investigational CliniMACS cell sorting device. (time frame: September 2006). 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 29 Jan 2009.