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Langerhans Cell HistiocytosisPhase 3NCT04773366

A Prospective Study for the Treatment of Children With Newly Diagnosed LCH Using a Cytarabine Contained Protocol

A Phase 3 study testing Prednisone+Cytarabine+vincristine, Prednisone+Cytarabine+vincristine+Mercaptopurine and Prednisone+vincristine+Mercaptopurine in people with Langerhans Cell Histiocytosis, run by Shanghai Children's Medical Center at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

From January 2010 to December 2014, 150 children with MS-LCH were treated in our hospital following a LCH II (Arm B) based protocol. Treatment was based on a modification of the LCH-II (Arm B) based protocol. Read more about this study

Who is it for?
Ages 1 day to 18 years
Conditions the study is for
Langerhans Cell Histiocytosis
What is being tested?
Prednisone+Cytarabine+vincristine, Prednisone+Cytarabine+vincristine+Mercaptopurine and Prednisone+vincristine+Mercaptopurine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
200 participants
Where
1 siteChina
Study dates
1 Jul 2018to 30 Jun 2026
Phase
Phase 3
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 1 day to 18 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Age under 18 years
  • Newly diagnosed LCH：Morphologic identification of the characteristic LCH cells, positive staining of the lesional cells with CD1α and/or Langerin
  • No congenital immunodeficiency, HIV infection, or prior organ transplant
  • No previous chemotherapy/target therapy/radiation, if any steroid applied, total prior steroids dosage < prednisone 280 mg/m2

Who cannot join

  • Patients have overwhelming infection, and a life expectancy of < 2 weeks

Trial locations and contacts

1 site in 1 country.

Meng Su, MD contact

0086-18817821853

sumeng@scmc.com.cn

Ya-Li Han, MD contact

0086-21-38626288

hanyali@scmc.com.cn

China1 site, 1 recruiting

  • Shanghai Children's Medical Center

    Shanghai

    Yi-Jin Gao, 021-38626161, gaoyijin@scmc.com.cn

    Recruiting

Other trials in China

About this study

Official title: A Prospective Institutional Study for the Treatment of Children With Newly Diagnosed Langerhans Cell Histiocytosis Using a Cytarabine Contained Protocol

From January 2010 to December 2014, 150 children with MS-LCH were treated in our hospital following a LCH II (Arm B) based protocol. Treatment was based on a modification of the LCH-II (Arm B) based protocol. However, the continuation treatment was extended to 56 weeks and etoposide was omitted from the continuation treatment.

For the 59 patients with RO involvement (RO+) (the lungs are not considered a RO in the current study), the rapid response rate (week 6) was 61.0% and the 3-year overall survival (OS) 73.4±5.9%. Rapid responders had a better 3-year survival rate than poor responders (90.9±5.0% vs. 45.7±11.0%, P<0.001). The 3-year OS in the current study is 10~20% lower than the rates reported by Gadner et al. and Morimoto et al.. We have not yet adopted effective salvage therapies for RO+ patients with recurrent disease. During the time of this study, cladribine was unavailable. Second-line therapy for non-responders or patients with disease reactivation was individualized treatment based on the physician's experience. An effective salvage therapy is essential for this high-risk group.

For 91without RO involvement (RO-), 78 patients (85.7%) were rapid responders at week 6. The 3-year cumulative reactivation rate was 10.7% for RO- patients. No death occurred in this subgroup, with a 3-year OS of 100% in RO- patients. Compared to the LCH II and LCH III trials, the current study had a more intensive initial treatment regimen for RO- patients. However, the addition of etoposide to prednisone and vincristine in the initial therapy did not increase the 6-week response rate for RO- patients (85.7% in this study compared to 83% in the LCH II study and 86% in the LCH III study). Surprisingly, with a relatively intense initial treatment, a relatively low 3-year cumulative reactivation rate was observed in RO- patients in the current study. This result suggests that the initial treatment intensity and duration of continuation therapy both impact disease reactivation. The intensity of induction can affect the degree of disease resolution. Insufficient treatment intensity might lead to late relapse. Similarity to that observed has been in other childhood hematological malignancies. This finding deserves to be tested in prospective clinical trials with long-term follow-up. Cytarabine has been applied for patients with LCH but has never been evaluated in our hospital prospectively. In this study, we administer a cytarabine contained protocol to patients with multisystem involvement with or without risk organs involvement. The treatment results will be compared with our historical studies.

Read the detailed description

All patients with de novo pathological confirmed LCH enrolled in this study will be classified into 4 groups. Group 1: Multisystem patients (≥2 organs/systems) with involvement of one or more "Risk" organs" (hematopoietic system, liver or spleen);Group 2:Multisystem patients, but without involvement of "Risk" organs; Group 3: Single system, Multifocal+ Single system, unifocal and special site@ (Isolated lesion of special site)+ Single system, unifocal and CNS risk+Single system, unifocal i.e. thyroid, lung, thymus, hypothalamic-pituitary+Single system, unifocal and other functionally critical anatomical sites; Group 4: Single system, unifocal i.e. bone, skin or lymph node (not the draining lymph node of another LCH lesion). For patients in Group 1, a 6-week initial treatment, a 16-week consolidation continuation treatment and a 26-week maintenance continuation treatment containing cytarabine is applied. For patients in Group 2, a 6-week initial treatment containing cytarabine and a 46-week continuation treatment (without cytarabine) is applied. For patients in Group 3,a 6-week initial treatment and a 46-week continuation treatment (without cytarabine) is applied. For patients in Group 4, only local therapy followed by wait-and-see strategy is applied.

Being tested
Prednisone+Cytarabine+vincristine, Prednisone+Cytarabine+vincristine+Mercaptopurine, Prednisone+vincristine+Mercaptopurine, Prednisone+vincristine, Local therapy
Keywords
Langerhans cell histiocytosis, pediatric patients, cytarabine, treatment outcome
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.

  • Prednisone+Cytarabine+vincristineDrug

    Group 1 initial treatment (W1~W6). Prednisone 40mg/m2×4w, taper 2w; Vincristine 1.5mg/m2 iv d1 of w1,2,3,4,5,6; Cytarabine 100mg/m2 iv/IH d1-4 q2w (w1,3,5)

  • Prednisone+Cytarabine+vincristine+MercaptopurineDrug

    Group 1 Consolidation continuation treatment (W7~W22) . Prednisone 40mg/m2 d1-5 q3w (w7,10,13,16,19,22); VCR 1.5/m2 iv d1 q3w (w7,10,13,16,19,22); Cytarabine 100mg/m2 iv/IH d1-4 q3w (w7,10,13,16,19,22); 6-MP 50mg/m2/d,po,qn

  • Prednisone+Cytarabine+vincristine+MercaptopurineDrug

    Group 1 Maintenance continuation treatment (W25~52) . Prednisone 40mg/m2 d1-5 q3w; Vincristine 1.5/m2 iv d1 q3w; Cytarabine 100mg/m2 iv/IH d1-4 q6w ×3 times (w25,31,37); 6-MP 50mg/m2/d,po,qn

  • Prednisone+Cytarabine+vincristineDrug

    Group 2 Initial treatment (W1~W6) . Prednisone 40mg/m2×4w, taper 2w; Vincristine 1.5mg/m2 iv d1 of w1,2,3,4,5,6; Cytarabine 100mg/m2 iv/IH d1-4 q2w (w1,3,5)

  • Prednisone+vincristine+MercaptopurineDrug

    Group 2 continuation treatment (W7~W52) . Prednisone 40mg/m2 d1-5 q3w; VCR 1.5/m2 iv d1 q3w; 6-MP 50mg/m2/d,po,qn

  • Prednisone+vincristineDrug

    Group 3 Initial treatment (W1~W6) . Prednisone 40mg/m2×4w, taper 2w; Vincristine 1.5mg/m2 iv d1 of w1,2,3,4,5,6

  • Prednisone+vincristineDrug

    . Group 3 Continuation treatment (W7~W52)Prednisone 40mg/m2 d1-5 q3w; Vincristine 1.5/m2 iv d1 q3w

  • Local therapyOther

    Local therapy/wait and see. Group 4

Study groups in NCT04773366
Study groupRoleWhat they receive
Group 1ExperimentalMultisystem patients (≥2 organs/systems) with involvement of one or more "Risk" organs, i.e. hematopoietic system, liver or spleen. All patients in this group receive an initial therapy (Week 1~6) followed by a consolidation continuation therapy (Week 7~22) and maintenance continuation therapy (Week 25~52).
Receives: Drug: Prednisone+Cytarabine+vincristine; Drug: Prednisone+Cytarabine+vincristine+Mercaptopurine
Group 2ExperimentalMultisystem patients, but without involvement of "Risk" organs. All patients in this group receive an initial therapy (Week 1~6) followed by continuation therapy (Week 7~52).
Receives: Drug: Prednisone+Cytarabine+vincristine; Drug: Prednisone+vincristine+Mercaptopurine
Group 3ExperimentalIncludes patients with single system, multifocal or with single system, unifocal and special site (Isolated lesion of special site) or with single system, unifocal and CNS risk or with single system, unifocal i.e. thyroid, lung, thymus, hypothalamic-pituitary or with single system, unifocal and other functionally critical anatomical sites. All patients in this group receive an initial therapy (Week 1~6) followed by continuation therapy (Week 7~52).
Receives: Drug: Prednisone+vincristine
Group 4ExperimentalPatients with single system, unifocal i.e. bone, skin or lymph node (not the draining lymph node of another LCH lesion). All patients in this group enter into observation after local therapy. Chemotherapy only apply to patients with disease reactivation during observation.
Receives: Other: Local therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Rate of responders after initial treatment for patients with risk organ involvement

    Rate of responders after initial treatment and consolidation continuation treatment. A good response is defined as complete resolution (no evidence of active disease) in risk organs.

    Measured: Evaluation at week 6 or 12

  2. Reactivation rate for all patients

    Reactivation is defined as progression or relapse in any organ or system after disease complete resolution (no evidence of active disease).

    Measured: Up to 5 years

Secondary outcomes (1)

  1. Overall survival for patients with risk organ involvement

    Overall survival is measured using the Kaplan-Meier method. From the day of diagnosis to death for any reason or to the date of the last follow-up contact.

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Feb 2021
  2. Study start1 Jul 2018
  3. Primary completion30 Jun 2023 (estimated)
  4. Study completion30 Jun 2026 (estimated)

Resources

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 3
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
All enrolled patients are stratified into 4 risk groups. Patients in each risk group are assigned to one treatment regimen.
Masking
None (open label)
Enrolment
200 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04773366
Sponsor's protocol ID
SCMC-LCH-2018
Status last verified
Jul 2022
First submitted
18 Feb 2021
Last updated
26 Jul 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Simko SJ, McClain KL, Allen CE. Up-front therapy for LCH: is it time to test an alternative to vinblastine/prednisone? Br J Haematol. 2015 Apr;169(2):299-301. doi: 10.1111/bjh.13208. Epub 2014 Nov 16. No abstract available.

    PubMed 25400231

  • Gadner H, Grois N, Potschger U, Minkov M, Arico M, Braier J, Broadbent V, Donadieu J, Henter JI, McCarter R, Ladisch S; Histiocyte Society. Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification. Blood. 2008 Mar 1;111(5):2556-62. doi: 10.1182/blood-2007-08-106211. Epub 2007 Dec 18.

    PubMed 18089850

  • Gadner H, Grois N, Arico M, Broadbent V, Ceci A, Jakobson A, Komp D, Michaelis J, Nicholson S, Potschger U, Pritchard J, Ladisch S; Histiocyte Society. A randomized trial of treatment for multisystem Langerhans' cell histiocytosis. J Pediatr. 2001 May;138(5):728-34. doi: 10.1067/mpd.2001.111331.

    PubMed 11343051

  • Egeler RM, de Kraker J, Voute PA. Cytosine-arabinoside, vincristine, and prednisolone in the treatment of children with disseminated Langerhans cell histiocytosis with organ dysfunction: experience at a single institution. Med Pediatr Oncol. 1993;21(4):265-70. doi: 10.1002/mpo.2950210406.

    PubMed 8469221

  • Weitzman S, Braier J, Donadieu J, Egeler RM, Grois N, Ladisch S, Potschger U, Webb D, Whitlock J, Arceci RJ. 2'-Chlorodeoxyadenosine (2-CdA) as salvage therapy for Langerhans cell histiocytosis (LCH). results of the LCH-S-98 protocol of the Histiocyte Society. Pediatr Blood Cancer. 2009 Dec 15;53(7):1271-6. doi: 10.1002/pbc.22229.

    PubMed 19731321

  • Donadieu J, Bernard F, van Noesel M, Barkaoui M, Bardet O, Mura R, Arico M, Piguet C, Gandemer V, Armari Alla C, Clausen N, Jeziorski E, Lambilliote A, Weitzman S, Henter JI, Van Den Bos C; Salvage Group of the Histiocyte Society. Cladribine and cytarabine in refractory multisystem Langerhans cell histiocytosis: results of an international phase 2 study. Blood. 2015 Sep 17;126(12):1415-23. doi: 10.1182/blood-2015-03-635151. Epub 2015 Jul 20.

    PubMed 26194764

  • Braier J, Rosso D, Pollono D, Rey G, Lagomarsino E, Latella A, Zubizarreta P. Symptomatic bone langerhans cell histiocytosis treated at diagnosis or after reactivation with indomethacin alone. J Pediatr Hematol Oncol. 2014 Jul;36(5):e280-4. doi: 10.1097/MPH.0000000000000165001.

    PubMed 24977402

  • Heritier S, Jehanne M, Leverger G, Emile JF, Alvarez JC, Haroche J, Donadieu J. Vemurafenib Use in an Infant for High-Risk Langerhans Cell Histiocytosis. JAMA Oncol. 2015 Sep;1(6):836-8. doi: 10.1001/jamaoncol.2015.0736. No abstract available.

    PubMed 26180941

  • Gao YJ, Su M, Tang JY, Pan C, Chen J. Treatment Outcome of Children With Multisystem Langerhans Cell Histiocytosis: The Experience of a Single Children's Hospital in Shanghai, China. J Pediatr Hematol Oncol. 2018 Jan;40(1):e9-e12. doi: 10.1097/MPH.0000000000001016.

    PubMed 29200145

  • Su M, Gao YJ, Pan C, Chen J, Tang JY. Outcome of children with Langerhans cell histiocytosis and single-system involvement: A retrospective study at a single center in Shanghai, China. Pediatr Hematol Oncol. 2018 Oct-Nov;35(7-8):385-392. doi: 10.1080/08880018.2018.1545814. Epub 2019 Jan 29.

    PubMed 30693828

  • Gadner H, Minkov M, Grois N, Potschger U, Thiem E, Arico M, Astigarraga I, Braier J, Donadieu J, Henter JI, Janka-Schaub G, McClain KL, Weitzman S, Windebank K, Ladisch S; Histiocyte Society. Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis. Blood. 2013 Jun 20;121(25):5006-14. doi: 10.1182/blood-2012-09-455774. Epub 2013 Apr 15.

    PubMed 23589673

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Prednisone+Cytarabine+vincristine, Prednisone+Cytarabine+vincristine+Mercaptopurine and Prednisone+vincristine+Mercaptopurine in people with Langerhans Cell Histiocytosis, run by Shanghai Children's Medical Center at 1 site in China.

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 4 inclusion and 1 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: status not confirmed, as of the sponsor's last update on 26 Jul 2022. 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 China. 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 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?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Meng Su, MD (0086-18817821853, sumeng@scmc.com.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rate of responders after initial treatment for patients with risk organ involvement (time frame: Evaluation at week 6 or 12). 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?

On the ClinicalTrials.gov record for NCT04773366, which also lists 11 linked publications.

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 26 Jul 2022.

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