Acute Myeloid LeukemiaPhase 2NCT00145626
HLA-Nonidentical Stem Cell and Natural Killer Cell Transplantation for Children Less the Two Years of Age With Hematologic Malignancies
A Phase 2 study testing Chemotherapy and antibodies, Miltenyi Biotec CliniMACS and Allogeneic stem cell transplantation in people with Acute Myeloid Leukemia and Acute Lymphocytic Leukemia, run by St. Jude Children's Research Hospital at 1 site in United States.
Trial summary
Recent studies of conventional chemotherapy for infants with high-risk hematologic malignancies show that the long-term disease-free survival is low. Although blood and marrow stem cell transplantation using an HLA identical sibling has improved the outcome for these children, less than 25% have this donor source… Read more about this study
- Who is it for?
- Ages Up to 24 months
- Conditions the study is for
- Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, Myelodysplasia
- What is being tested?
- Chemotherapy and antibodies, Miltenyi Biotec CliniMACS and Allogeneic stem cell transplantation
- 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
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- May 2004to Jul 2016
- 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 Up to 24 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Must have one of the following diagnosis:
- AML in remission or relapse (e.g., FAB M7 or biphenotypic leukemia)
- High-risk ALL in first remission (e.g., poor responder to prednisone, Ph+ ALL)
- ALL beyond first remission
- Secondary leukemia
- Primary myelodysplasia (including RAEB, RAEB-T, CMML, JCML, and JMML)
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- Chronic myeloid leukemia
- Histiocytoses (including multi-system Langerhans' cell histiocytosis and hemophagocytic lymphohistiocytosis
- HIV negative (date).
- Hepatitis B surface antigen negative (date).
- Hepatitis C antibody negative (date).
- Syphilis negative (date).
- Donor is equal to or greater than 3 on 6 HLA match (date).
- Not pregnant (negative pregnancy test).
- Not lactating.
- At least 18 years of age.
Who cannot join
- Patients greater than 24 months of age at the time of transplant.
- HLA-identical sibling donor is available.
- Cardiac function: shortening fraction <25%.
- Pulse oximetry oxygen saturation <92% on room air.
- Glomerular filtration rate less than 40 ml/min/1.73 m2 (may use Technetium-99 result for GFR).
- Direct bilirubin > 3 mg/dl.
Show all 10Show fewer
- SGPT > 500 U/L.
- Patients with previous allergy to mouse proteins.
- Patients with previous allergy to rabbit serum products.
- Patients with Down's syndrome
Trial locations and contacts
1 site in 1 country.
United States1 site
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
About this study
Recent studies of conventional chemotherapy for infants with high-risk hematologic malignancies show that the long-term disease-free survival is low. Although blood and marrow stem cell transplantation using an HLA identical sibling has improved the outcome for these children, less than 25% have this donor source available. Another option is haploidentical transplantation using a partially matched family member donor (i.e. parental donor).
Although haploidentical transplantation has proven curative for some patients, this procedure has been hindered by significant complications, primarily regimen-related toxicity including infection and graft versus host disease (GVHD). Building on prior institutional trials, this study will provide patients a haploidentical graft depleted of T lymphocytes using the investigational device, CliniMACS selection system. One week after the transplant procedure, patients will also receive an infusion of additional donor derived white blood cells called Natural Killer (NK) cells in an effort to decrease risks for rejection of the graft, disease relapse, and regimen related toxicity. The primary objective of the study is to evaluate 1 year survival in infants with high risk hematologic malignancies who receive this study treatment.
Read the detailed description
Secondary objectives for this study include the following:
- To estimate the incidence of three transplant-related adverse outcomes (i.e., regimen-related mortality, engraftment failure, and fatal acute GVHD) in the first 100 days after transplantation.
- To estimate the incidence of chronic graft-versus-host disease.
- To evaluate those factors that affect one-year survival.
- To assess the kinetics of lymphohematopoietic reconstitution.
- To assess the frequency and clinical relevance of minimal residual disease (MRD) before and after transplantation.
- To evaluate the incidence of and risk factors for long-term neurocognitive deficit and organ dysfunction.
- Conditions
- Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, Myelodysplasia, Chronic Myeloid Leukemia, Histiocytosis
- Being tested
- Chemotherapy and antibodies, Miltenyi Biotec CliniMACS, Allogeneic stem cell transplantation
- Keywords
- Stem cell transplantation, Stem cell transplant, Haploidentical transplant
- Medical subject headings
- Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Anemia, Refractory, with Excess of Blasts, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Histiocytosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Chemotherapy and antibodiesDrug
Also called Cyclophosphamide, Fludarabine, Thiotepa, Melphalan
Study participants will receive a non-TBI based preparative regimen consisting of Cyclophosphamide, fludarabine, thiotepa, melphalan, and muromonab-CD3 (OKT3) followed by an infusion of a T-lymphocyte depleted haploidentical hematopoietic stem cell graft. Seven days posttransplant, participants will receive an infusion of additional donor derived cells called NK cells.
Miltenyi Biotec CliniMACSDevice
Stem cell selection device
Allogeneic stem cell transplantationProcedure or surgery
Also called Haploidentical stem cell transplantation, Allogeneic stem cell transplant, Immunotherapy, Mismatched family member donor transplant
Allogeneic natural killer (NK)cell infusion
| Study group | Role | What they receive |
|---|---|---|
| Study Participants | Experimental | Participants who meet the eligibility criteria for this study. Donor cells will be obtained using the Miltenyi Biotec CliniMACS device.
Interventions: Chemotherapy and antibodies, allogeneic stem cell transplantation. Receives: Drug: Chemotherapy and antibodies; Device: Miltenyi Biotec CliniMACS; Procedure: Allogeneic stem cell transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
One-year Survival
The one-year survival of infants with high-risk hematologic malignancies who receive a haploidentical transplant procedure using a total body irradiation (TBI)-excluding conditioning regimen followed by an HLA-nonidentical family donor hematopoietic stem cell (HSC) graft depleted of T cells ex vivo using the CliniMACS CD34+ selection system, with a subsequent infusion of donor NK cells purified ex vivo using the CliniMACS CD3+ depletion and CD56+ enrichment system.
The Kaplan-Meier estimate for one-year survival is reported.
Measured: One year after transplant
Secondary outcomes (15)
Number of Transplant-Related Adverse Outcomes: Regimen-Related Mortality
The cumulative incidences of regimen-related mortality will be estimated using method of Kalbfleisch and Prentice.
Measured: 100 days post-transplantation
Number of Transplant-Related Adverse Outcomes: Engraftment Failure
Engraftment failure is defined as <10% donor cell chimerism at any time point between 28 and 100 days after transplant with no evidence of disease relapse or requiring stem cell boost.
Measured: 100 days post-transplantation
Number of Transplant-Related Adverse Outcomes: Fatal Acute Graft-Versus Host Disease (GVHD)
The cumulative incidence estimate for occurrence of fatal acute GVHD by the end of the first 100 days post-transplant was calculated using method of Kalbfleisch and Prentice.
Measured: 100 days post-transplantation
Number of Incidences of Chronic GVHD.
Chronic GVHD was graded according to Seattle Criteria: limited or extensive. Limited is defined as localized skin and/or hepatic dysfunction. Extensive is defined as one or more of the following:
- generalized skin involvement
- liver histology showing chronic aggressive hepatitis, bridging necrosis or cirrhosis
- eye dryness with Schirmer's test <5 mm wetting
- oral: involvement of salivary glands or oral mucosa
- other: another target organ involvement
Measured: Up to 5 years after transplant
Factors Affecting One-year Survival: Median Age of Donor at HSCT
Due to small sample size (n=14) and total number of events (n=7), the analysis to check the various factors that affect the one-year survival was not performed (using logistic and cox model).
Measured: Up to one year after transplant
Factors Affecting One-year Survival: Median Dose of CD34
Due to small sample size (n=14) and total number of events (n=7), the analysis to check the various factors that affect the one-year survival was not performed (using logistic and cox model).
Measured: Up to one year after transplant
Factors Affecting One-year Survival: Median Dose of NK Cells
Due to small sample size (n=14) and total number of events (n=7), the analysis to check the various factors that affect the one-year survival was not performed (using logistic and cox model).
Measured: Up to one year after transplant
Factors Affecting One-year Survival: Disease Status at HSCT
Due to small sample size (n=14) and total number of events (n=7), the analysis to check the various factors that affect the one-year survival was not performed (using logistic and cox model).
Measured: Up to one year after transplant
Factors Affecting One-year Survival: Donor Type
Due to small sample size (n=14) and total number of events (n=7), the analysis to check the various factors that affect the one-year survival was not performed (using logistic and cox model).
Measured: Up to one year after transplant
Factors Affecting One-year Survival: Match N/6 HLA Loci
HLA typing determined the degree of match by looking at 6 different HLA loci. The results indicate the number of the 6 loci that matched for each participant. Due to small sample size (n=14) and total number of events (n=7), the analysis to check the various factors that affect the one-year survival was not performed (using logistic and cox model).
Measured: Up to one year after transplant
Factors Affecting One-year Survival: Minimal Residual Disease (MRD)
Detection of leukemia blasts in bone marrow by flow cytometry
Measured: Up to one year after transplant
Incidence of and Risk Factors for Organ Dysfunction.
The organ dysfunction will be summarized using summary statistics and assessed in a longitudinal manner and analyzed accordingly.
Measured: Up to 5 Years after transplant
Incidence of and Risk Factors for Long-term Neurocognitive Deficit.
The long-term neurocognitive deficit will be summarized using summary statistics and assessed in a longitudinal manner and analyzed accordingly.
Measured: Up to 5 Years after transplant
Frequency of and Clinical Relevance of Minimal Residual Disease (MRD) Before and After Transplantation
The presence or absence of MRD before and after the bone marrow transplant (BMT) and its frequency distribution will be obtained for each time point separately.
Measured: Baseline before HSCT, 1 year post HSCT, and up to 5 years post HSCT
Kinetics of Lymphohematopoietic Reconstitution
The lymphohematopoietic reconstitution will be summarized using summary statistics and assessed in a longitudinal manner and analyzed accordingly.
Measured: From 0-3 months after HSCT through 4-5 years after HSCT
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2005 (estimated)
- Study startMay 2004
- Primary completionMar 2015
- Study completionJul 2016
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 Acute Myeloid 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Jude Children's Research Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Assisi Foundation
- Responsible party
- Sponsor
- Investigators
- Brandon Triplett, MD, Principal investigator, St. Jude Children's Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00145626
- Sponsor's protocol ID
- INFT2
- Other IDs
- NCI-2011-03671
- Status last verified
- May 2017
- First submitted
- 1 Sep 2005
- Last updated
- 19 Jun 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- HLA-Nonidentical Stem Cell and Natural Killer Cell Transplantation for Children Less the Two Years of Age With Hematologic Malignancies
- ClinicalTrials.gov ID
- NCT00145626
- Acronym / sponsor ID
- INFT2
- Conditions
- Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, Myelodysplasia, Chronic Myeloid Leukemia, Histiocytosis
- Keywords
- Stem cell transplantation, Stem cell transplant, Haploidentical transplant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- St. Jude Children's Research HospitalUniversity, hospital or other
- Collaborators
- Assisi Foundation
- Study start
- May 2004
- Primary completion
- Mar 2015 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 5 Sep 2005 (estimated)
- Results
- Posted 14 Dec 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Recent studies of conventional chemotherapy for infants with high-risk hematologic malignancies show that the long-term disease-free survival is low. Although blood and marrow stem cell transplantation using an HLA identical sibling has improved the outcome for these children, less than 25% have this donor source available. Another option is haploidentical transplantation using a partially matched family member donor (i.e. parental donor).
Although haploidentical transplantation has proven curative for some patients, this procedure has been hindered by significant complications, primarily regimen-related toxicity including infection and graft versus host disease (GVHD). Building on prior institutional trials, this study will provide patients a haploidentical graft depleted of T lymphocytes using the investigational device, CliniMACS selection system. One week after the transplant procedure, patients will also receive an infusion of additional donor derived white blood cells called Natural Killer (NK) cells in an effort to decrease risks for rejection of the graft, disease relapse, and regimen related toxicity. The primary objective of the study is to evaluate 1 year survival in infants with high risk hematologic malignancies who receive this study treatment.
Detailed description
Secondary objectives for this study include the following:
- To estimate the incidence of three transplant-related adverse outcomes (i.e., regimen-related mortality, engraftment failure, and fatal acute GVHD) in the first 100 days after transplantation.
- To estimate the incidence of chronic graft-versus-host disease.
- To evaluate those factors that affect one-year survival.
- To assess the kinetics of lymphohematopoietic reconstitution.
- To assess the frequency and clinical relevance of minimal residual disease (MRD) before and after transplantation.
- To evaluate the incidence of and risk factors for long-term neurocognitive deficit and organ dysfunction.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Study Participants | Experimental | Drug: Chemotherapy and antibodies, Device: Miltenyi Biotec CliniMACS, Procedure: Allogeneic stem cell transplantationParticipants who meet the eligibility criteria for this study. Donor cells will be obtained using the Miltenyi Biotec CliniMACS device. Interventions: Chemotherapy and antibodies, allogeneic stem cell transplantation. |
Who may qualify
- Ages
- Up to 24 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (16 listed)
- AML in remission or relapse (e.g., FAB M7 or biphenotypic leukemia)
- High-risk ALL in first remission (e.g., poor responder to prednisone, Ph+ ALL)
- ALL beyond first remission
- Secondary leukemia
- Primary myelodysplasia (including RAEB, RAEB-T, CMML, JCML, and JMML)
Key exclusion criteria (10 listed)
- Patients greater than 24 months of age at the time of transplant.
- HLA-identical sibling donor is available.
- Cardiac function: shortening fraction <25%.
- Pulse oximetry oxygen saturation <92% on room air.
- Glomerular filtration rate less than 40 ml/min/1.73 m2 (may use Technetium-99 result for GFR).
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 |
|---|---|---|
| Chemotherapy and antibodiesAlso: Cyclophosphamide, Fludarabine, Thiotepa, MelphalanStudy participants will receive a non-TBI based preparative regimen consisting of Cyclophosphamide, fludarabine, thiotepa, melphalan, and muromonab-CD3 (OKT3) followed by an infusion of a T-lymphocyte depleted haploidentical hematopoietic stem cell graft. Seven days posttransplant, participants will receive an infusion of additional donor derived cells called NK cells. | Drug | Study Participants |
| Miltenyi Biotec CliniMACSStem cell selection device | Device | Study Participants |
| Allogeneic stem cell transplantationAlso: Haploidentical stem cell transplantation, Allogeneic stem cell transplant, Immunotherapy, Mismatched family member donor transplantAllogeneic natural killer (NK)cell infusion | Procedure or surgery | Study Participants |
Primary outcome
One-year Survival
Time frame: One year after transplant
The one-year survival of infants with high-risk hematologic malignancies who receive a haploidentical transplant procedure using a total body irradiation (TBI)-excluding conditioning regimen followed by an HLA-nonidentical family donor hematopoietic stem cell (HSC) graft depleted of T cells ex vivo using the CliniMACS CD34+ selection system, with a subsequent infusion of donor NK cells purified ex vivo using the CliniMACS CD3+ depletion and CD56+ enrichment system. The Kaplan-Meier estimate for one-year survival is reported.
15 secondary outcomes
Number of Transplant-Related Adverse Outcomes: Regimen-Related Mortality
Time frame: 100 days post-transplantation
Number of Transplant-Related Adverse Outcomes: Engraftment Failure
Time frame: 100 days post-transplantation
Number of Transplant-Related Adverse Outcomes: Fatal Acute Graft-Versus Host Disease (GVHD)
Time frame: 100 days post-transplantation
Number of Incidences of Chronic GVHD.
Time frame: Up to 5 years after transplant
Factors Affecting One-year Survival: Median Age of Donor at HSCT
Time frame: Up to one year after transplant
Factors Affecting One-year Survival: Median Dose of CD34
Time frame: Up to one year after transplant
Factors Affecting One-year Survival: Median Dose of NK Cells
Time frame: Up to one year after transplant
Factors Affecting One-year Survival: Disease Status at HSCT
Time frame: Up to one year after transplant
Factors Affecting One-year Survival: Donor Type
Time frame: Up to one year after transplant
Factors Affecting One-year Survival: Match N/6 HLA Loci
Time frame: Up to one year after transplant
Factors Affecting One-year Survival: Minimal Residual Disease (MRD)
Time frame: Up to one year after transplant
Incidence of and Risk Factors for Organ Dysfunction.
Time frame: Up to 5 Years after transplant
Incidence of and Risk Factors for Long-term Neurocognitive Deficit.
Time frame: Up to 5 Years after transplant
Frequency of and Clinical Relevance of Minimal Residual Disease (MRD) Before and After Transplantation
Time frame: Baseline before HSCT, 1 year post HSCT, and up to 5 years post HSCT
Kinetics of Lymphohematopoietic Reconstitution
Time frame: From 0-3 months after HSCT through 4-5 years after HSCT
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jun 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- St. Jude Children's Research HospitalLink provided by the sponsor.
- Clinical Trials Open at St. JudeLink 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.
Brandon Triplett, MD 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 Chemotherapy and antibodies, Miltenyi Biotec CliniMACS and Allogeneic stem cell transplantation in people with Acute Myeloid Leukemia and Acute Lymphocytic 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 16 inclusion and 10 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 19 Jun 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 14 Dec 2015). 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?
One-year Survival (time frame: One year after transplant). 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 19 Jun 2017.