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

July 23, 2022 updated by: Shanghai Children's Medical Center

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

200

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
      • Shanghai, China
        • Recruiting
        • Shanghai Children's Medical Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 day to 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

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

Exclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group 1

Multisystem 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).
Drug: Prednisone+Cytarabine+vincristine
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)
Drug: Prednisone+Cytarabine+vincristine+Mercaptopurine
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
Drug: Prednisone+Cytarabine+vincristine+Mercaptopurine
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
Drug: Prednisone+Cytarabine+vincristine
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)
Experimental: Group 2

Multisystem 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).
Drug: Prednisone+Cytarabine+vincristine
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)
Drug: Prednisone+Cytarabine+vincristine
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)
Drug: Prednisone+vincristine+Mercaptopurine
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
Experimental: Group 3

Includes 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).
Drug: Prednisone+vincristine
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
Drug: Prednisone+vincristine
. Group 3 Continuation treatment (W7~W52)Prednisone 40mg/m2 d1-5 q3w; Vincristine 1.5/m2 iv d1 q3w
Experimental: Group 4

Patients 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.
Other: Local therapy
Local therapy/wait and see. Group 4

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of responders after initial treatment for patients with risk organ involvement
Time Frame: Evaluation at week 6 or 12
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.
Evaluation at week 6 or 12
Reactivation rate for all patients
Time Frame: Up to 5 years
Reactivation is defined as progression or relapse in any organ or system after disease complete resolution (no evidence of active disease).
Up to 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival for patients with risk organ involvement
Time Frame: Up to 5 years
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.
Up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shanghai Children's Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2018

Primary Completion (Anticipated)

June 30, 2023

Study Completion (Anticipated)

June 30, 2026

Study Registration Dates

First Submitted

February 18, 2021

First Submitted That Met QC Criteria

February 25, 2021

First Posted (Actual)

February 26, 2021

Study Record Updates

Last Update Posted (Actual)

July 26, 2022

Last Update Submitted That Met QC Criteria

July 23, 2022

Last Verified

July 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SCMC-LCH-2018

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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