LeukemiaPhase 1/2NCT00582816
Haploidentical Transplant With NK Cell Infusion for Pediatric Acute Leukemia and Solid Tumors
A Phase 1/2 study testing Clinimacs Cell Separation System, conditioning chemotherapy and DLI in people with Leukemia and Solid Tumors, run by University of Wisconsin, Madison at 1 site in United States.
Trial summary
This study will assess the feasibility of utilizing a reduced intensity conditioning regimen, in the setting of haploidentical transplantation, for patients with recurrent acute lymphoblastic leukemia (ALL), AML and high risk or refractory solid tumors. Read more about this study
- Who is it for?
- Ages 6 months to 25 years
- Conditions the study is for
- Leukemia, Solid Tumors
- What is being tested?
- Clinimacs Cell Separation System, conditioning chemotherapy and DLI
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2008to Aug 2015
- 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 6 months to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Solid tumors that have failed auto transplant or are ineligible to receive auto transplant
- Relapsed AML in 1st relapse or 2nd or 3rd CR
- Relapsed ALL if they fail to attain an initial remission or if they relapse within 1 year following the discontinuation of chemotherapy.
- Greater than or equal to 6 months and <26 years old
- Suitable haploidentical donor available
Who cannot join
- Leukemia with >25% blasts in bone marrow at the time of admission to the HSCT unit.
- Serum bilirubin >3 mg/dl
- GFR <40 ml/min/1.73 mw
- Cardiac left ventricular ejection fraction <40%
- HIV+
- Pregnant
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Reduced Intensity Haploidentical Transplantation With NK Cell Infusion for Pediatric Acute Leukemia and High Risk Solid Tumors, BMT06407
This study will assess the feasibility of utilizing a reduced intensity conditioning regimen, in the setting of haploidentical transplantation, for patients with recurrent acute lymphoblastic leukemia (ALL), AML and high risk or refractory solid tumors. In addition, the feasibility and safety of administering post-transplant NK cell infusions will be evaluated. Data obtained from this study will help determine the efficacy of allogeneic HSCT in the treatment of pediatric sarcomas and add to the small body of literature utilizing haploidentical HSCT to treat acute leukemia in pediatric patients. This study will also further elucidate the role of NK cells in mediating a graft vs. tumor effect in allogeneic HSCT. The main benefit to society is that this study will explore a novel therapy for children with highly refractory cancer who are felt to be incurable with conventional approaches. If feasibility is demonstrated, and there is evidence of anti-tumor activity, then this will open up a new area of clinical research to better define the efficacy of this approach for specific childhood malignancies.
- Conditions
- Leukemia, Solid Tumors
- Being tested
- Clinimacs Cell Separation System, conditioning chemotherapy, DLI
- Keywords
- Recurrent or Refractory Leukemia or Solid Tumors in Pediatrics
- Medical subject headings
- Leukemia, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Clinimacs Cell Separation SystemDevice
Depletion of T-cells
conditioning chemotherapyDrug
Methylprednisolone, Equine ATG, Cyclosporine, Fludarabine, Melphalan, Thiotepa and Rituximab.
DLIOther
NK Cell selected DLI
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | patients will undergo a standard pre-transplant evaluation, but will also have blood drawn to evaluate their HLA class I killer immunoglobulin-like receptor (KIR) ligand typing. Parents will undergo KIR genotyping and phenotyping, and a donor will be selected based on which parent shows the greatest degree of KIR receptor-ligand mismatching. Once the donor has been selected he/she will undergo a peripheral blood stem cell (PBSC) collection utilizing G-CSF and GM-CSF for stem cell mobilization. The PBSC collection will be performed utilizing standard procedures. The PBSC will then be processed in the UW BMT Laboratory in order to deplete the graft of T cells. This will be accomplished using the CliniMACS cell separation system. T cell depletion is a standard procedure for patients receiving haploidentical stem cell grafts. The resulting stem cell product will be analyzed for T cell, stem cell and NK cell content. Receives: Device: Clinimacs Cell Separation System; Drug: conditioning chemotherapy; Other: DLI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Grade III or IV GVHD
Skin Grade III: Stage 0-4 GVHD, where 0 is no rash and 4 is generalized erythroderma with bullous formation and/or with desquamation Grade IV: Stage 4 GVHD, generalized erythroderma with bullous formation and/or with desquamation
GI (diarrhea) Grade III: Stage 2-4 GVHD, where 2 is > 1000 mL/day but ≤ 1500 mL/day or 556-833 mL/m2, and 4 is severe abdominal pain +/- ileus or stool with frank blood or melena Grade IV: Stage 0-4 GVHD, where 0 is < 500 mL/day or 280 mL/m2, and 4 is severe abdominal pain +/- ileus or stool with frank blood or melena
Overall:
Grade III: Grade III Skin and/or GI as well as bilirubin 3.1-15 mg/dl Grade IV: Grade IV Skin and/or GI as well as bilirubin > 15 mg/dl
Measured: Day 100
Engraftment Failure
Utilize non-myeloablative conditioning regimen in the haploidentical transplant setting.
Primary engraftment failure: failure to achieve ANC of ≥500/uL prior to day +28 Late engraftment failure: Initial engraftment achieved with ANC ≥500/uL by day +28 followed by loss of graft Autologous Cells Infused: achieved hematologic recovery following infusions of autologous stem cells Second Haploidentical Transplant: re-transplantation utilizing an alternative haploidentical donor
Measured: 28 days
Number of Days Until Engraftment Criteria Were Met
Utilize non-myeloablative conditioning regimen in the haploidentical transplant setting. Engraftment is defined as achieving an absolute neutrophil count ≥ 500 by 28 days post-transplant; platelets and red blood cells will also be measured up to 28 days:
- Neutrophils: ≥500/uL for 3 days
- Platelets: ≥20 K/uL for 3 days without transfusion
- Red blood cells: the date of the last RBC transfusion after achieving transfusion independence Results are reported as number of days until engraftment criteria was met, per neutrophil, platelet and red blood cell measurements, above.
Measured: 28 days
Mortality Rate
Mortality rate at 100 days post-transplant.
Measured: 100 days post-transplant
Secondary outcomes (3)
NK Expression Levels
Natural Killer (NK) cell expression levels will be explored. Blood samples will be collected at months 1, 2, 3, 6, 9, and 12.
Measured: Up to 12 months
Association Between Parental KIR Genotypes and NK Cell Cytotoxicities
NK cells express killer-cell immunoglobulin-like receptors (KIR) and have cytotoxic activity. The association between NK cell cytotoxicity over time and KIR genotypes will be examined. Blood samples will be collected at months 1, 2, 3, 6, 9, and 12.
Measured: Day 60
Analysis of NK Cell KIR Expression Over Time
NK cell KIR expression over time will be examined. Blood samples will be collected at months 1, 2, 3, 6, 9, and 12.
Measured: Up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Dec 2007 (estimated)
- Study startAug 2008
- Primary completionAug 2015
- Study completionAug 2015
Why it stopped: toxicity
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by University of Wisconsin, MadisonThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Collaborators
- Miltenyi Biomedicine GmbH
- Responsible party
- Sponsor
- Investigators
- Kenneth DeSantes, M.D., Principal investigator, University of Wisconsin, Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00582816
- Sponsor's protocol ID
- BMT06407
- Other IDs
- H-2006-0297, 2012-0661, A536700, SMPH\PEDIATRICS\PEDIATRICS, NCI-2011-00687
- Status last verified
- Jul 2017
- First submitted
- 19 Dec 2007
- Last updated
- 9 Dec 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reduced Intensity Haploidentical Transplantation With NK Cell Infusion for Pediatric Acute Leukemia and High Risk Solid Tumors, BMT06407
- ClinicalTrials.gov ID
- NCT00582816
- Acronym / sponsor ID
- BMT06407
- Conditions
- Leukemia, Solid Tumors
- Keywords
- Recurrent or Refractory Leukemia or Solid Tumors in Pediatrics
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: toxicity
- Enrolment
- 9 participants (actual)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Collaborators
- Miltenyi Biomedicine GmbH
- Study start
- Aug 2008
- Primary completion
- Aug 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 28 Dec 2007 (estimated)
- Results
- Posted 19 Jul 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will assess the feasibility of utilizing a reduced intensity conditioning regimen, in the setting of haploidentical transplantation, for patients with recurrent acute lymphoblastic leukemia (ALL), AML and high risk or refractory solid tumors. In addition, the feasibility and safety of administering post-transplant NK cell infusions will be evaluated. Data obtained from this study will help determine the efficacy of allogeneic HSCT in the treatment of pediatric sarcomas and add to the small body of literature utilizing haploidentical HSCT to treat acute leukemia in pediatric patients. This study will also further elucidate the role of NK cells in mediating a graft vs. tumor effect in allogeneic HSCT. The main benefit to society is that this study will explore a novel therapy for children with highly refractory cancer who are felt to be incurable with conventional approaches. If feasibility is demonstrated, and there is evidence of anti-tumor activity, then this will open up a new area of clinical research to better define the efficacy of this approach for specific childhood malignancies.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Device: Clinimacs Cell Separation System, Drug: conditioning chemotherapy, Other: DLIpatients will undergo a standard pre-transplant evaluation, but will also have blood drawn to evaluate their HLA class I killer immunoglobulin-like receptor (KIR) ligand typing. Parents will undergo KIR genotyping and phenotyping, and a donor will be selected based on which parent shows the greatest degree of KIR receptor-ligand mismatching. Once the donor has been selected he/she will undergo a peripheral blood stem cell (PBSC) collection utilizing G-CSF and GM-CSF for stem cell mobilization. The PBSC collection will be performed utilizing standard procedures. The PBSC will then be processed in the UW BMT Laboratory in order to deplete the graft of T cells. This will be accomplished using the CliniMACS cell separation system. T cell depletion is a standard procedure for patients receiving haploidentical stem cell grafts. The resulting stem cell product will be analyzed for T cell, stem cell and NK cell content. |
Who may qualify
- Ages
- 6 months to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- Solid tumors that have failed auto transplant or are ineligible to receive auto transplant
- Relapsed AML in 1st relapse or 2nd or 3rd CR
- Relapsed ALL if they fail to attain an initial remission or if they relapse within 1 year following the discontinuation of chemotherapy.
- Greater than or equal to 6 months and <26 years old
- Suitable haploidentical donor available
Key exclusion criteria (6 listed)
- Leukemia with >25% blasts in bone marrow at the time of admission to the HSCT unit.
- Serum bilirubin >3 mg/dl
- GFR <40 ml/min/1.73 mw
- Cardiac left ventricular ejection fraction <40%
- HIV+
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 |
|---|---|---|
| Clinimacs Cell Separation SystemDepletion of T-cells | Device | 1 |
| conditioning chemotherapyMethylprednisolone, Equine ATG, Cyclosporine, Fludarabine, Melphalan, Thiotepa and Rituximab. | Drug | 1 |
| DLINK Cell selected DLI | Other | 1 |
Primary outcome
Grade III or IV GVHD
Time frame: Day 100
Skin Grade III: Stage 0-4 GVHD, where 0 is no rash and 4 is generalized erythroderma with bullous formation and/or with desquamation Grade IV: Stage 4 GVHD, generalized erythroderma with bullous formation and/or with desquamation GI (diarrhea) Grade III: Stage 2-4 GVHD, where 2 is > 1000 mL/day but ≤ 1500 mL/day or 556-833 mL/m2, and 4 is severe abdominal pain +/- ileus or stool with frank blood or melena Grade IV: Stage 0-4 GVHD, where 0 is < 500 mL/day or 280 mL/m2, and 4 is severe abdominal pain +/- ileus or stool with frank blood or melena Overall: Grade III: Grade III Skin and/or GI as well as bilirubin 3.1-15 mg/dl Grade IV: Grade IV Skin and/or GI as well as bilirubin > 15 mg/dl
Engraftment Failure
Time frame: 28 days
Utilize non-myeloablative conditioning regimen in the haploidentical transplant setting. Primary engraftment failure: failure to achieve ANC of ≥500/uL prior to day +28 Late engraftment failure: Initial engraftment achieved with ANC ≥500/uL by day +28 followed by loss of graft Autologous Cells Infused: achieved hematologic recovery following infusions of autologous stem cells Second Haploidentical Transplant: re-transplantation utilizing an alternative haploidentical donor
Number of Days Until Engraftment Criteria Were Met
Time frame: 28 days
Utilize non-myeloablative conditioning regimen in the haploidentical transplant setting. Engraftment is defined as achieving an absolute neutrophil count ≥ 500 by 28 days post-transplant; platelets and red blood cells will also be measured up to 28 days: * Neutrophils: ≥500/uL for 3 days * Platelets: ≥20 K/uL for 3 days without transfusion * Red blood cells: the date of the last RBC transfusion after achieving transfusion independence Results are reported as number of days until engraftment criteria was met, per neutrophil, platelet and red blood cell measurements, above.
Mortality Rate
Time frame: 100 days post-transplant
Mortality rate at 100 days post-transplant.
3 secondary outcomes
NK Expression Levels
Time frame: Up to 12 months
Association Between Parental KIR Genotypes and NK Cell Cytotoxicities
Time frame: Day 60
Analysis of NK Cell KIR Expression Over Time
Time frame: Up to 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- University of Wisconsin Carbone Cancer CenterLink 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.
Kenneth DeSantes, M.D. principal investigator
University of Wisconsin, Madison
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 Clinimacs Cell Separation System, conditioning chemotherapy and DLI in people with Leukemia and Solid Tumors, run by University of Wisconsin, Madison 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 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 Dec 2019. 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 19 Jul 2017). 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?
Grade III or IV GVHD (time frame: Day 100). The study lists 4 primary outcomes in all. 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 9 Dec 2019.