Hemophagocytic LymphohistiocytosisPhase 2/3NCT00176826
T-Cell Depletion and Stem Cell Transplant for Immune Deficiencies and Histiocytic Disorders
A Phase 2/3 study testing Stem Cell Transplant and Myeloablative conditioning regimen in people with Hemophagocytic Lymphohistiocytosis and X-Linked Lymphoproliferative Disorders, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
Trial summary
The hypothesis is to determine if a preparative regimen of busulfan, cyclophosphamide, and antithymocyte globulin (ATG) plus allogeneic stem cell transplantation will be effective in the treatment of immune deficiencies and histiocytic disorders. Read more about this study
- Who is it for?
- Ages Up to 55 years
- Conditions the study is for
- Hemophagocytic Lymphohistiocytosis, X-Linked Lymphoproliferative Disorders, Chediak-Higashi Syndrome
- What is being tested?
- Stem Cell Transplant and Myeloablative conditioning regimen
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2000to Aug 2015
- Phase
- Phase 2/3
- 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
- Any patient from birth to < 55 years of age fulfilling the following criteria will be eligible for this study.
- Patients meeting clinical diagnostic criteria for Hemophagocytic Lymphohistiocytosis (HLH)
- Patients meeting clinical diagnostic criteria or genetic diagnosis of X-linked lymphoproliferative disorder (XLP) and whose disease is ACTIVE but STABLE, or NON-ACTIVE/QUIESCENT.
- Patients with Chediak-Higashi Syndrome who meet the following diagnostic criteria and whose disease is ACTIVE but STABLE, or NON-ACTIVE/QUIESCENT as defined in Appendix V of the study protocol.
- Patients with Viral Associated Hemophagocytic Syndrome (VAHS) - if relapsed after other therapy or supportive care. Diagnostic criteria as above for HLH. Disease status must be ACTIVE but STABLE, or NON-ACTIVE/QUIESCENT as defined in Appendix V. It is cautioned that many patients with HLH or familial hemophagocytic lymphohistiocytosis (FHL) will have a viral infection at time of initial presentation and may therefore be misdiagnosed as having VAHS.
- Griscelli Syndrome
Show all 21Show fewer
- Primary immune deficiencies with non-genotypic identical donors only.
- Progressive Langerhans cell histiocytosis unresponsive to standard therapy.
- Other non-malignant hematological disorders in which stem cell transplant with a myeloablative regimen is indicated.
- Diamond Blackfan Anemia if transfusion dependent
- Schwachman Diamond Syndrome: with cytopenias or transformation to myelodysplastic syndrome (MDS)
- Kostman's Syndrome (if ANC <500 without GCSF support, or transformation to MDS)
- Congenital dyserythropoietic anemia if transfusion dependent
- Amegakaryocytic thrombocytopenia if baseline platelet counts <20,000 or requiring transfusions.
- Cardiac, hepatic, renal and pulmonary function deemed adequate for high dose chemotherapy with stem cell rescue as per institutional standards. General guidelines are as follows:
- Cardiac: Asymptomatic or, if symptomatic, then left ventricular ejection fraction at rest must be > 40% and must improve with exercise, or shortening fraction by echocardiogram must be within institutional normals
- Hepatic: < 3 x normal SGOT and < 2.5 mg/dL serum bilirubin
- Renal: Serum creatinine within normal range, or if serum creatinine outside normal range then creatinine clearance or glomerular filtration study should be > 50% of normal.
- Pulmonary: Asymptomatic or, if symptomatic, diffusing capacity of the lung for carbon monoxide (DLCO) > 45% of predicted (corrected for hemoglobin). For children unable to perform pulmonary function testing, then oxygen saturation should be >95%.
- Availability of a suitable allogeneic bone marrow donor as per current institutional guidelines for non-T cell depleted hematopoietic stem cell transplant (HSCT).
- Patients who have undergone previous stem cell transplant (SCT) and failed engraftment or who had relapse of their disease are considered eligible if they meet other eligibility criteria and if the second SCT would occur 6 months or more after the first. If the first SCT preparative regimen was of a non-myeloablative intensity then the second SCT could be performed earlier when the acute toxicity from that procedure was resolved.
Who cannot join
- Patients who are moribund or whose life expectancy is severely limited by disease other than their underlying disorder. Karnofsky performance status < 70% or Lansky < 50% for patients < 16 years.
- Patients with hemophagocytic disorders secondary to underlying malignancy.
- Patients who have ACTIVE/UNSTABLE disease as defined in Appendix V.
- Significant active infections, including Human Immunodeficiency Virus (HIV).
- Age > 55 years.
- Not providing informed consent.
Trial locations and contacts
1 site in 1 country.
United States1 site
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, 55455
About this study
Official title: In-vivo T-cell Depletion and Hematopoietic Stem Cell Transplantation for Life-Threatening Immune Deficiencies and Histiocytic Disorders
The hypothesis is to determine if a preparative regimen of busulfan, cyclophosphamide, and antithymocyte globulin (ATG) plus allogeneic stem cell transplantation will be effective in the treatment of immune deficiencies and histiocytic disorders.
Read the detailed description
Subjects will begin chemotherapy as a preparative regimen, which is intended to completely eliminate their defective immune system and bone marrow. The preparative regimen consists of the chemotherapy drugs (busulfan, cyclophosphamide, and antithymocyte globulin (ATG)).
Transplantation: subjects will then have a source of blood stem cells (bone marrow) from their donor administered into their catheter. Medication will be given to help prevent Graft-Versus Host Disease (GVHD). The ATG will help to deplete the donor stem cells of the type of cells that can cause GVHD and will also help to promote engraftment of the new stem cells.
Recovery Phase: The second phase of treatment consists of a period after transplantation during which we wait for the return of bone marrow function. This usually takes two to four weeks. Subjects will be given a blood cell growth factor, G-CSF, to help speed recovery of the white blood cells and potentially decrease the risk of infection and decrease the time until the bone marrow recovers.
- Conditions
- Hemophagocytic Lymphohistiocytosis, X-Linked Lymphoproliferative Disorders, Chediak-Higashi Syndrome, Griscelli Syndrome, Immunologic Diseases, Langerhans-Cell Histiocytosis
- Being tested
- Stem Cell Transplant, Myeloablative conditioning regimen
- Keywords
- Stem Cell Transplant, T-cell depletion, immune deficiencies, Busulfan pharmacokinetics, Non-Malignant Hematological Disorders
- Medical subject headings
- Lymphohistiocytosis, Hemophagocytic, Lymphoproliferative Disorders, Chediak-Higashi Syndrome, Immune System Diseases, Histiocytosis, Langerhans-Cell, Hematologic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stem Cell TransplantProcedure or surgery
Also called HSCT
Infusion of hematopoietic stem cells (bone marrow, cord blood, peripheral blood stem cells) following myeloablative conditioning regimen.
Myeloablative conditioning regimenDrug
Also called Busulfex, Cytoxan, ATG
Busulfan intravenously for 4 days followed by cyclophosphamide intravenously for 4 days. Rabbit ATG is given intravenously for 4 doses pre-transplant.
| Study group | Role | What they receive |
|---|---|---|
| Intent-To-Treat | Experimental | Patients who were treated with chemotherapies (myeloablative conditioning regimen) and stem cell transplant. Busulfan intravenously for 4 days followed by cyclophosphamide intravenously for 4 days. Rabbit ATG is given intravenously for 4 doses pre-transplant. Receives: Procedure: Stem Cell Transplant; Drug: Myeloablative conditioning regimen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Transplant Engraftment
Measured: Day 100 Post Transplant
Secondary outcomes (6)
Number of Patients With Treatment Related Mortality.
Measured: Day 100 Post Transplant
Number of Patients Surviving (Disease-free)
Measured: 1 year
Number of Patients With Grade II-IV Graft-Versus-Host Disease (GVHD)
Measured: Day 100 Post Transplant
Number of Patients With Graft Failure
Measured: Day 100 Post transplant
Number of Patients With III-IV Graft-Versus-Host Disease (GVHD)
Measured: Day 100 Post Transplant
Number of Patients Surviving (Disease-free)
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2005 (estimated)
- Study startSep 2000
- Primary completionAug 2012
- Study completionAug 2015
Why it stopped: Replaced by another protocol
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 Hemophagocytic LymphohistiocytosisStudies of the same condition, open and under way.
- More trials run by Masonic Cancer Center, University of MinnesotaThe 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 2/3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Masonic Cancer Center, University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Angela Smith, MD, Principal investigator, University of Minnesota Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00176826
- Sponsor's protocol ID
- UMN-MT2000-21
- Other IDs
- 0010M66781
- Status last verified
- May 2015
- First submitted
- 12 Sep 2005
- Last updated
- 23 Jan 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- In-vivo T-cell Depletion and Hematopoietic Stem Cell Transplantation for Life-Threatening Immune Deficiencies and Histiocytic Disorders
- ClinicalTrials.gov ID
- NCT00176826
- Acronym / sponsor ID
- UMN-MT2000-21
- Conditions
- Hemophagocytic Lymphohistiocytosis, X-Linked Lymphoproliferative Disorders, Chediak-Higashi Syndrome, Griscelli Syndrome, Immunologic Diseases, Langerhans-Cell Histiocytosis
- Keywords
- Stem Cell Transplant, T-cell depletion, immune deficiencies, Busulfan pharmacokinetics, Non-Malignant Hematological Disorders
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Replaced by another protocol
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Masonic Cancer Center, University of MinnesotaUniversity, hospital or other
- Study start
- Sep 2000
- Primary completion
- Aug 2012 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 15 Sep 2005 (estimated)
- Results
- Posted 28 Apr 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The hypothesis is to determine if a preparative regimen of busulfan, cyclophosphamide, and antithymocyte globulin (ATG) plus allogeneic stem cell transplantation will be effective in the treatment of immune deficiencies and histiocytic disorders.
Detailed description
Subjects will begin chemotherapy as a preparative regimen, which is intended to completely eliminate their defective immune system and bone marrow. The preparative regimen consists of the chemotherapy drugs (busulfan, cyclophosphamide, and antithymocyte globulin (ATG)).
Transplantation: subjects will then have a source of blood stem cells (bone marrow) from their donor administered into their catheter. Medication will be given to help prevent Graft-Versus Host Disease (GVHD). The ATG will help to deplete the donor stem cells of the type of cells that can cause GVHD and will also help to promote engraftment of the new stem cells.
Recovery Phase: The second phase of treatment consists of a period after transplantation during which we wait for the return of bone marrow function. This usually takes two to four weeks. Subjects will be given a blood cell growth factor, G-CSF, to help speed recovery of the white blood cells and potentially decrease the risk of infection and decrease the time until the bone marrow recovers.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intent-To-Treat | Experimental | Procedure: Stem Cell Transplant, Drug: Myeloablative conditioning regimenPatients who were treated with chemotherapies (myeloablative conditioning regimen) and stem cell transplant. Busulfan intravenously for 4 days followed by cyclophosphamide intravenously for 4 days. Rabbit ATG is given intravenously for 4 doses pre-transplant. |
Who may qualify
- Ages
- Up to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (21 listed)
- Any patient from birth to < 55 years of age fulfilling the following criteria will be eligible for this study.
- Patients meeting clinical diagnostic criteria for Hemophagocytic Lymphohistiocytosis (HLH)
- Patients meeting clinical diagnostic criteria or genetic diagnosis of X-linked lymphoproliferative disorder (XLP) and whose disease is ACTIVE but STABLE, or NON-ACTIVE/QUIESCENT.
- Patients with Chediak-Higashi Syndrome who meet the following diagnostic criteria and whose disease is ACTIVE but STABLE, or NON-ACTIVE/QUIESCENT as defined in Appendix V of the study protocol.
- Patients with Viral Associated Hemophagocytic Syndrome (VAHS) - if relapsed after other therapy or supportive care. Diagnostic criteria as above for HLH. Disease status must be ACTIVE but STABLE, or NON-ACTIVE/QUIESCENT as defined in Appendix V. It is cautioned that many patients with HLH or familial hemophagocytic lymphohistiocytosis (FHL) will have a viral infection at time of initial presentation and may therefore be misdiagnosed as having VAHS.
Key exclusion criteria (6 listed)
- Patients who are moribund or whose life expectancy is severely limited by disease other than their underlying disorder. Karnofsky performance status < 70% or Lansky < 50% for patients < 16 years.
- Patients with hemophagocytic disorders secondary to underlying malignancy.
- Patients who have ACTIVE/UNSTABLE disease as defined in Appendix V.
- Significant active infections, including Human Immunodeficiency Virus (HIV).
- Age > 55 years.
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 |
|---|---|---|
| Stem Cell TransplantAlso: HSCTInfusion of hematopoietic stem cells (bone marrow, cord blood, peripheral blood stem cells) following myeloablative conditioning regimen. | Procedure or surgery | Intent-To-Treat |
| Myeloablative conditioning regimenAlso: Busulfex, Cytoxan, ATGBusulfan intravenously for 4 days followed by cyclophosphamide intravenously for 4 days. Rabbit ATG is given intravenously for 4 doses pre-transplant. | Drug | Intent-To-Treat |
Primary outcome
Time to Transplant Engraftment
Time frame: Day 100 Post Transplant
6 secondary outcomes
Number of Patients With Treatment Related Mortality.
Time frame: Day 100 Post Transplant
Number of Patients Surviving (Disease-free)
Time frame: 1 year
Number of Patients With Grade II-IV Graft-Versus-Host Disease (GVHD)
Time frame: Day 100 Post Transplant
Number of Patients With Graft Failure
Time frame: Day 100 Post transplant
Number of Patients With III-IV Graft-Versus-Host Disease (GVHD)
Time frame: Day 100 Post Transplant
Number of Patients Surviving (Disease-free)
Time frame: 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2018.
- 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.
Angela Smith, MD principal investigator
University of Minnesota Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Stem Cell Transplant and Myeloablative conditioning regimen in people with Hemophagocytic Lymphohistiocytosis and X-Linked Lymphoproliferative Disorders, run by Masonic Cancer Center, University of Minnesota 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 21 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 23 Jan 2018. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 28 Apr 2014). 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?
Time to Transplant Engraftment (time frame: Day 100 Post 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 23 Jan 2018; AzTrials last refreshed its copy on 7 Nov 2026.