Crizotinib Combined With Etoposide Capsule Followed by Auto-HSCT for Relapsed and Refractory ALK+ ALCL

Study Overview
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Brief Summary
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To observe the safety, tolerability and clinical effects of crizotinib combined with etoposide capsule followed by autologous hematopoietic stem cell transplantation (Auto-HSCT) for patients with relapsed and refractory ALK-positive Anaplastic Large Cell Lymphoma.

Detailed Description
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This is a prospective, open-label, one-arm, multicenter clinical trial, aimed to evaluate the safety, tolerability, and efficacy of crizotinib combined with etoposide followed by autologous hematopoietic stem cell transplantation for relapsed and refractory ALK-positive ALCL. A total of 20 patients are planned to be enrolled into the study. Patients with diagnosis of relapsed and refractory ALK-positive ALCL will be treated with crizotinib plus etoposide capsules followed by autologous hematopoietic stem cell transplantation. The primary end points are objective responder rate (ORR) and progression free survival(PFS) and the secondary end points include overall survival(OS) , and adverse events.

Official Title
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Single-arm, Multi-center Clinical Study of Crizotinib Combined With Etoposide Capsule Followed by Auto-HSCT for Relapsed and Refractory Anaplastic Lymphoma Kinase (ALK)-Positive Anaplastic Large Cell Lymphoma (ALCL)

Conditions
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ALK-Positive Anaplastic Large Cell Lymphoma

Intervention / Treatment
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* Drug: Crizotinib
* Drug: Etoposide Capsule
* Procedure: Auto-HSCT


Participation Criteria
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Eligibility Criteria
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Criteria: Inclusion Criteria: age:14-65 years;Eastern Cooperative Oncology Group (ECOG)score≤3;expected survival≥3 months patients with ALK-positive Anaplastic Large Cell Lymphoma diagnosed by immuno-histochemistry (IHC) or fluorescence in situ hybridization (FISH); Refractory or relapse after at least 4 cycles of CHOP（cyclophosphamide, hydroxydaunomycin, Oncovin, and prednisone）regimen acceptable hematological indicators, no chemotherapy contraindications; total bilirubin ≤ 1.5 times the upper limit of normal (ULN), alanine aminotransferase (ALT) ≤ 2.5 x upper age limit (ULN), if the abnormal laboratory parameters are considered to be caused by lymphoma, patients Eligible conditions should be adjusted to be incorporated into the group; At least one measurable lesion by CT or PET-CT（Positron Emission Tomography-Computed Tomography）; exclude other major diseases, normal heart and lung function; Female patients of childbearing age are negative for pregnancy test; Cooperate with follow-up; There are no other related treatments including traditional Chinese medicine, immunotherapy, and biologic therapy (except for the treatment of anti-bone metastases and other symptoms); Signing informed consent *: Pathological histology must be consulted by a pathologist at a provincial hospital. Exclusion Criteria: rejecting providing blood preparation; allergic to drug in this study and with metabolic block; rejecting adopting reliable contraceptive method in pregnancy or lactation period; uncontrolled internal medicine disease(including uncontrolled diabetes,severe incompetence cardiac,lung,liver and pancreas）； with severe infection; with primary or secondary central nervous system tumor invasion; with immunotherapy or radiotherapy contraindication; ever suffered with malignant tumor; having peripheral nervous system disorder or dysphrenia; with no legal capacity,medical or ethical reasons affecting research proceeding; participating other clinical trials simultaneously; adopting other anti-tumor medicine excluding this research; Patients with immunodeficiency, such as primary immunodeficiency syndrome or organ transplant recipients Human immunodeficiency virus (HIV)-positive patients the researchers considering it inappropriate to participate in the study.

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Crizotinib + etoposide capsule+Auto-HSCT<br>Crizotinib and etoposide capsule followed by autologous hematopoietic stem cell transplantation. Crizotinib: 250mg, bis in die （BID）, PO. Etoposide capsule:50mg, quaque die （QD）, PO, d1-10，21days for one cycle. Patients will receive the treatment of crizotinib and etoposide capsule, and those who have achieved CR（complete response）or VGPR（very good partial response）will undergo the Auto-HSCT. | Drug: Crizotinib<br>* 250mg, BID, PO<br>Drug: Etoposide Capsule<br>* 50mg, QD, PO, d1-10，21days for one cycle<br>Procedure: Auto-HSCT<br>* Auto-HSCT will be performed with patients who have achieved CR or VGPR.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | Objective Responder Rate | up to 24 months | 
| PFS | Progression Free Survival | up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OS | Overall Survival | up to 24 months | 
| adverse events | Number of patients with adverse events | up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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crizotinib, etoposide, autologous hematopoietic stem cell transplantation, ORR, OS, PFS, adverse events