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

NCT ID: NCT04773366

Last Updated: 2022-07-26

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-01
• Study Completion Date: 2026-06-30

Brief 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. 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.

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.

Conditions

Langerhans Cell Histiocytosis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

Prednisone+Cytarabine+vincristine

Intervention Type: DRUG

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+Mercaptopurine

Intervention Type: DRUG

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+Mercaptopurine

Intervention Type: DRUG

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

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).

Group Type: EXPERIMENTAL

Prednisone+Cytarabine+vincristine

Intervention Type: DRUG

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+Mercaptopurine

Intervention Type: DRUG

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

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).

Group Type: EXPERIMENTAL

Prednisone+vincristine

Intervention Type: DRUG

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+vincristine

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Local therapy

Intervention Type: OTHER

Local therapy/wait and see. Group 4

Interventions

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)

Intervention Type: 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

Intervention Type: 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

Intervention Type: 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)

Intervention Type: 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

Intervention Type: 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

Intervention Type: DRUG

Prednisone+vincristine

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

Intervention Type: DRUG

Local therapy

Local therapy/wait and see. Group 4

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Children's Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yi-Jin Gao, MD

Role: PRINCIPAL_INVESTIGATOR

Shanghai Children's Medical Center

Locations

Shanghai Children's Medical Center

Shanghai, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Meng Su, MD

Role: CONTACT

sumeng@scmc.com.cn

0086-18817821853

Ya-Li Han, MD

Role: CONTACT

hanyali@scmc.com.cn

0086-21-38626288

Facility Contacts

Yi-Jin Gao

Role: primary

gaoyijin@scmc.com.cn

021-38626161

References

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Other Identifiers

SCMC-LCH-2018

Identifier Type: -

Identifier Source: org_study_id