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

Sponsor

Mingzhi Zhang (Other)

Overall Status

Unknown status

CT.gov ID

NCT03707847

Collaborator

(none)

Enrollment

Location

Arm

28.1

Anticipated Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
ALK-Positive Anaplastic Large Cell Lymphoma	Drug: Crizotinib Drug: Etoposide Capsule Procedure: Auto-HSCT	Phase 4

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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)

Actual Study Start Date :

Oct 1, 2018

Anticipated Primary Completion Date :

Feb 1, 2020

Anticipated Study Completion Date :

Feb 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Crizotinib + etoposide capsule+Auto-HSCT 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 250mg, BID, PO Drug: Etoposide Capsule 50mg, QD, PO, d1-10，21days for one cycle Procedure: Auto-HSCT Auto-HSCT will be performed with patients who have achieved CR or VGPR.

Arm

Intervention/Treatment

Experimental: Crizotinib + etoposide capsule+Auto-HSCT

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

250mg, BID, PO

Drug: Etoposide Capsule

50mg, QD, PO, d1-10，21days for one cycle

Procedure: Auto-HSCT

Auto-HSCT will be performed with patients who have achieved CR or VGPR.

Outcome Measures

Primary Outcome Measures

ORR [up to 24 months]
Objective Responder Rate
PFS [up to 24 months]
Progression Free Survival

Secondary Outcome Measures

OS [up to 24 months]
Overall Survival
adverse events [up to 24 months]
Number of patients with adverse events

Eligibility Criteria

Criteria

Ages Eligible for Study:

14 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.