Histiocytosis, Langerhans-cellPhase 2NCT00618540
Reduced Intensity Hematopoietic Cell Transplantation for Patients With Resistant Langerhans Cell Histiocytosis
A Phase 2 study testing alemtuzumab, fludarabine phosphate and melphalan in people with Histiocytosis, Langerhans-cell, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
Trial summary
RATIONALE: Giving a monoclonal antibody, such as alemtuzumab, and chemotherapy drugs, such as fludarabine and melphalan, before a donor stem cell transplant helps stop the patient's immune system from rejecting the donor's stem cells and helps stop the growth of abnormal cells. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Histiocytosis, Langerhans-cell
- What is being tested?
- alemtuzumab, fludarabine phosphate and melphalan
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2007to May 2013
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Histologically confirmed Langerhans cell histiocytosis (LCH) by demonstration of CD1a positivity or Birbeck granules in lesions
- Considered poor-risk, defined as multisystem disease with involvement of one or more risk organs (i.e., liver, spleen, lungs, and/or hematopoietic system)
- No isolated "lung only" LCH
- Progressive disease after one of the following treatments:
- LCH-III protocol or other standard LCH-directed therapies
- At least 1 course of the current salvage protocol (i.e., LCH-2 2005) or similar therapy (e.g., cytosine arabinoside or cladribine-based regimens)
Show all 17Show fewer
- HLA-matched related or unrelated donor OR unrelated umbilical cord blood (UCB) available
- 1 locus mismatch for donor allowed
- Up to 2 loci mismatch for unrelated UCB allowed
- Any hematologic status (transfusion support allowed)
- Adequate hepatic, renal, cardiac, and pulmonary function to undergo reduced-intensity hematopoietic cell transplantation (RI-HCT) including the following:
- Transaminases < 5 times upper limit of normal (ULN)
- Bilirubin < 3 times ULN (unless secondary to hepatic LCH)
- Creatinine ≤ 2 mg/dL (adults) (if creatinine > 1.2 OR history of renal dysfunction, must have estimated creatinine clearance > 40 mL/min)
- Creatinine clearance > 40 mL/min (pediatrics)
- Glomerular filtration rate ≥ 50mL/min
- Negative pregnancy test
Who cannot join
- Decompensated congestive heart failure, uncontrolled arrhythmia, or left ventricular ejection fraction ≥ 35%
- Pulmonary failure (i.e., requiring mechanical ventilation) unless secondary to active underlying LCH
- Isolated liver sclerosis or pulmonary fibrosis unless secondary to active underlying LCH
- Uncontrolled active life-threatening infection
- Pregnant or nursing
- Less than 4 weeks after last attempted salvage chemotherapy treatment
- Other concurrent chemotherapy agents (e.g., methotrexate) during entire transplantation period up to day 100 post-transplantation
Trial locations and contacts
1 site in 1 country.
United States1 site
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, 55455
About this study
RATIONALE: Giving a monoclonal antibody, such as alemtuzumab, and chemotherapy drugs, such as fludarabine and melphalan, before a donor stem cell transplant helps stop the patient's immune system from rejecting the donor's stem cells and helps stop the growth of abnormal cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil before and after transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well giving alemtuzumab together with fludarabine and melphalan followed by a donor stem cell transplant works in treating young patients with resistant Langerhans cell histiocytosis.
Read the detailed description
OBJECTIVES:
Primary
- To determine the overall and disease-free survival of poor-risk pediatric patients with Langerhans cell histiocytosis at 1 and 3 years after reduced-intensity hematopoietic cell transplantation (RI-HCT).
Secondary
- To determine day 100 transplantation-related mortality.
- To determine the incidence of hematopoietic recovery and chimerism at day 100 and at 1 year post RI-HCT.
- To determine the incidence of grades II-IV and III-IV acute graft-versus-host disease (GVHD).
- To determine the incidence of chronic GVHD.
OUTLINE: This is a multicenter study.
- Non-myeloablative conditioning: Patients receive alemtuzumab intravenously (IV) over 2 hours on days -8 to -4, fludarabine phosphate IV over 30-60 minutes on days -7 to -3, and melphalan IV over 15-30 minutes on day -2. Some patients may receive anti-thymocyte globulin IV on days -6 to -2 instead of alemtuzumab.
- Graft-versus-host disease prophylaxis and immunosuppression: Patients receive cyclosporine A (CSA) IV or orally 2-3 times daily beginning on day -3 and continuing until day 50 post transplantation, followed by a taper over 8 weeks in the absence of GVHD or donor lymphocyte infusion given for decreasing donor chimerism. Patients with mismatched donors (any source) and those receiving peripheral blood stem cells also receive mycophenolate mofetil (MMF) IV or orally 2-3 times daily beginning on day -3 and continuing to day 30 or 7 days after engraftment, whichever day is later, in the absence of GVHD. In patients with acute GVHD requiring systemic therapy, Mycophenolate mofetil (MMF) may be stopped 7 days after initiation of systemic therapy.
- Allogeneic hematopoietic stem cell infusion: Patients undergo infusion of bone marrow (preferred) or peripheral blood stem cells on day 0. Patients also receive filgrastim (G-CSF) subcutaneously or IV beginning on day 8 and continuing until blood counts recover for 2 consecutive days.
- Donor lymphocyte infusion (DLI): Patients with mixed chimerism (i.e., < 95% donor) and those with < 50% donor T-cell engraftment at any engraftment assessment time point are eligible for DLI, in the absence of GVHD. If mixed chimerism persists, escalating doses of CD3-positive lymphocytes are administered every 3-4 weeks, in the absence of GVHD.
After completion of study therapy, patients are followed from engraftment through day 100, and then at 6 months, 1 year, and annually thereafter for 2-5 years.
- Conditions
- Histiocytosis, Langerhans-cell
- Being tested
- alemtuzumab, fludarabine phosphate, melphalan, stem cell transplantation
- Keywords
- childhood Langerhans cell histiocytosis
- Medical subject headings
- Histiocytosis, Langerhans-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
alemtuzumabBiological
Also called Campath(R)
Administered intravenously (IV) 0.2 mg/kg on Days -8 through -4.
Also called Fludara(R)
Administered 30 mg/m2 intravenously (IV) over 30-60 min on Days -7 through -3. (dose adjust if age <12 months)
melphalanDrug
Also called Alkeran
Administered 140 mg/m2 intravenously (IV) over 30 min on Day -2 (dose adjust if age <12 months)
stem cell transplantationProcedure or surgery
Also called Stem cell transplant
Administered as allogeneic hematopoietic, peripheral blood or umbilical cord blood transplantation
| Study group | Role | What they receive |
|---|---|---|
| Alemtuzumab | Experimental | Patients administered with alemtuzumab, fludarabine phosphate, melphalan and donor stem cell transplantation in children with resistant Langerhans cell histiocytosis. Receives: Biological: alemtuzumab; Drug: fludarabine phosphate; Drug: melphalan; Procedure: stem cell transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival
Count of patients alive at 1 and 3 years. Deaths from any cause are events. Surviving patients are censored at the date of last contact.
Measured: Year 1, Year 3
Disease-free Survival at 12 Months Post Transplantation
This outcome is defined as survival with resolution of LCH at 12 months post transplant.
Unresolved disease for over 12 months post-transplant, progressive disease after this time period, recurrence of disease and death from any cause are considered events.
Those who survive with resolution of disease are censored at the date of last contact.
Measured: Year 1
Secondary outcomes (6)
Transplantation-related Death
Count of patients who died by day 100 related to the transplantation.
Measured: Day 100
Neutrophil Engraftment
Incidence of neutrophil recovery and donor chimerism at Day 100.
Measured: Day 100
Incidence of Grade II-IV Acute Graft-versus-host-disease (GVHD)
The occurrence of skin, gastrointestinal or liver abnormalities fulfilling the criteria of Grades II, III and/or IV acute GVHD are considered events (Appendix II). Patients without acute GvHD will be censored at the time of death or last follow-up. Patients that survive <21 days and listed as not evaluable will be excluded. Patients receiving a second transplant will be censored at the time of second transplant.
Measured: Day 100 and Month 6
Incidence of Chronic GVHD
Occurrence of symptoms in any organ system fulfilling the criteria of limited or extensive chronic GvHD (Appendix III), among patients surviving > 90 days with evidence of engraftment. Patients without chronic GvHD will be censored at time of death or last follow-up.
Measured: Day 100 and Month 6
Platelet Engraftment
Incidence of platelet recovery and donor chimerism at Day 100.
Measured: Day 100
Incidence of Grade III-IV Acute Graft-versus-host-disease (GVHD)
The occurrence of skin, gastrointestinal or liver abnormalities fulfilling the criteria of Grades II, III and/or IV acute GVHD are considered events (Appendix II). Patients without acute GvHD will be censored at the time of death or last follow-up. Patients that survive <21 days and listed as not evaluable will be excluded. Patients receiving a second transplant will be censored at the time of second transplant.
Measured: Day 100 and Month 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2008 (estimated)
- Study startJan 2007
- Primary completionMay 2013
- Study completionMay 2013
Why it stopped: Slow accrual
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 Histiocytosis, Langerhans-cellStudies 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 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, Principal investigator, Masonic Cancer Center, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00618540
- Sponsor's protocol ID
- 2007UC002
- Other IDs
- UMN-0612M98407, LCH-HCT-2006, UMN-MT2006-07
- Status last verified
- Dec 2017
- First submitted
- 19 Feb 2008
- Last updated
- 28 Dec 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reduced Intensity Hematopoietic Cell Transplantation for Patients With Resistant Langerhans Cell Histiocytosis
- ClinicalTrials.gov ID
- NCT00618540
- Acronym / sponsor ID
- 2007UC002
- Conditions
- Histiocytosis, Langerhans-cell
- Keywords
- childhood Langerhans cell histiocytosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow accrual
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Masonic Cancer Center, University of MinnesotaUniversity, hospital or other
- Study start
- Jan 2007
- Primary completion
- May 2013 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 20 Feb 2008 (estimated)
- Results
- Posted 3 Nov 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Giving a monoclonal antibody, such as alemtuzumab, and chemotherapy drugs, such as fludarabine and melphalan, before a donor stem cell transplant helps stop the patient's immune system from rejecting the donor's stem cells and helps stop the growth of abnormal cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil before and after transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well giving alemtuzumab together with fludarabine and melphalan followed by a donor stem cell transplant works in treating young patients with resistant Langerhans cell histiocytosis.
Detailed description
OBJECTIVES:
Primary
- To determine the overall and disease-free survival of poor-risk pediatric patients with Langerhans cell histiocytosis at 1 and 3 years after reduced-intensity hematopoietic cell transplantation (RI-HCT).
Secondary
- To determine day 100 transplantation-related mortality.
- To determine the incidence of hematopoietic recovery and chimerism at day 100 and at 1 year post RI-HCT.
- To determine the incidence of grades II-IV and III-IV acute graft-versus-host disease (GVHD).
- To determine the incidence of chronic GVHD.
OUTLINE: This is a multicenter study.
- Non-myeloablative conditioning: Patients receive alemtuzumab intravenously (IV) over 2 hours on days -8 to -4, fludarabine phosphate IV over 30-60 minutes on days -7 to -3, and melphalan IV over 15-30 minutes on day -2. Some patients may receive anti-thymocyte globulin IV on days -6 to -2 instead of alemtuzumab.
- Graft-versus-host disease prophylaxis and immunosuppression: Patients receive cyclosporine A (CSA) IV or orally 2-3 times daily beginning on day -3 and continuing until day 50 post transplantation, followed by a taper over 8 weeks in the absence of GVHD or donor lymphocyte infusion given for decreasing donor chimerism. Patients with mismatched donors (any source) and those receiving peripheral blood stem cells also receive mycophenolate mofetil (MMF) IV or orally 2-3 times daily beginning on day -3 and continuing to day 30 or 7 days after engraftment, whichever day is later, in the absence of GVHD. In patients with acute GVHD requiring systemic therapy, Mycophenolate mofetil (MMF) may be stopped 7 days after initiation of systemic therapy.
- Allogeneic hematopoietic stem cell infusion: Patients undergo infusion of bone marrow (preferred) or peripheral blood stem cells on day 0. Patients also receive filgrastim (G-CSF) subcutaneously or IV beginning on day 8 and continuing until blood counts recover for 2 consecutive days.
- Donor lymphocyte infusion (DLI): Patients with mixed chimerism (i.e., < 95% donor) and those with < 50% donor T-cell engraftment at any engraftment assessment time point are eligible for DLI, in the absence of GVHD. If mixed chimerism persists, escalating doses of CD3-positive lymphocytes are administered every 3-4 weeks, in the absence of GVHD.
After completion of study therapy, patients are followed from engraftment through day 100, and then at 6 months, 1 year, and annually thereafter for 2-5 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Alemtuzumab | Experimental | Biological: alemtuzumab, Drug: fludarabine phosphate, Drug: melphalan, Procedure: stem cell transplantationPatients administered with alemtuzumab, fludarabine phosphate, melphalan and donor stem cell transplantation in children with resistant Langerhans cell histiocytosis. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (17 listed)
- Histologically confirmed Langerhans cell histiocytosis (LCH) by demonstration of CD1a positivity or Birbeck granules in lesions
- Considered poor-risk, defined as multisystem disease with involvement of one or more risk organs (i.e., liver, spleen, lungs, and/or hematopoietic system)
- Progressive disease after one of the following treatments:
- HLA-matched related or unrelated donor OR unrelated umbilical cord blood (UCB) available
- Any hematologic status (transfusion support allowed)
Key exclusion criteria (7 listed)
- Decompensated congestive heart failure, uncontrolled arrhythmia, or left ventricular ejection fraction ≥ 35%
- Pulmonary failure (i.e., requiring mechanical ventilation) unless secondary to active underlying LCH
- Isolated liver sclerosis or pulmonary fibrosis unless secondary to active underlying LCH
- Uncontrolled active life-threatening infection
- Pregnant or nursing
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 |
|---|---|---|
| alemtuzumabAlso: Campath(R)Administered intravenously (IV) 0.2 mg/kg on Days -8 through -4. | Biological | Alemtuzumab |
| fludarabine phosphateAlso: Fludara(R)Administered 30 mg/m2 intravenously (IV) over 30-60 min on Days -7 through -3. (dose adjust if age <12 months) | Drug | Alemtuzumab |
| melphalanAlso: AlkeranAdministered 140 mg/m2 intravenously (IV) over 30 min on Day -2 (dose adjust if age <12 months) | Drug | Alemtuzumab |
| stem cell transplantationAlso: Stem cell transplantAdministered as allogeneic hematopoietic, peripheral blood or umbilical cord blood transplantation | Procedure or surgery | Alemtuzumab |
Primary outcome
Overall Survival
Time frame: Year 1, Year 3
Count of patients alive at 1 and 3 years. Deaths from any cause are events. Surviving patients are censored at the date of last contact.
Disease-free Survival at 12 Months Post Transplantation
Time frame: Year 1
This outcome is defined as survival with resolution of LCH at 12 months post transplant. Unresolved disease for over 12 months post-transplant, progressive disease after this time period, recurrence of disease and death from any cause are considered events. Those who survive with resolution of disease are censored at the date of last contact.
6 secondary outcomes
Transplantation-related Death
Time frame: Day 100
Neutrophil Engraftment
Time frame: Day 100
Incidence of Grade II-IV Acute Graft-versus-host-disease (GVHD)
Time frame: Day 100 and Month 6
Incidence of Chronic GVHD
Time frame: Day 100 and Month 6
Platelet Engraftment
Time frame: Day 100
Incidence of Grade III-IV Acute Graft-versus-host-disease (GVHD)
Time frame: Day 100 and Month 6
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Dec 2017.
- 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 principal investigator
Masonic Cancer Center, University of Minnesota
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 alemtuzumab, fludarabine phosphate and melphalan in people with Histiocytosis, Langerhans-cell, 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 17 inclusion and 7 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 28 Dec 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 3 Nov 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?
Overall Survival (time frame: Year 1, Year 3). The study lists 2 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 28 Dec 2017.