Chidamide Combined With Clad/Gem/Bu With AutoSCT in R/R Diffuse Large B Cell Lymphoma

Lymphoma Clinical Trial

Official title:

Chidamide Combined With Cladribine/Gemcitabine/Busulfan (ChiCGB) With Autologous Stem-Cell Transplantation in Relapsed and Refractory Diffuse Large B Cell Lymphoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03151876
• Other study ID #: ChiCGB-DLBCL
• Status: Recruiting
• Phase: Phase 2
• Start date: June 12, 2017
• Est. completion date: December 2021

Study information

• Verified date: July 2018
• Source: Sichuan University
• Contact: Jie Ji, MD
• Phone: 86-28-85422370
• Email: JieJi[@]scu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical research study is to evaluate effectiveness and safety of ChiCGB regimen( chidamide, cladribine, gemcitabine and busulfan).

Busulfan are designed to kill cancer cells by binding to DNA (the genetic material of cells), which may cause cancer cells to die.

Gemcitabine and cladribine are designed to disrupt the growth of cancer cells, which may cause cancer cells to die. It may help to increase the effect of busulfan on cancer cells by not allowing these cells to repair the DNA damage caused by busulfan.

Chidamide is designed to open up the DNA and allow greater access to drugs that bind to DNA, such as cladribine, gemcitabine, busulfan.

Description:

Study Groups:

If you are found to be eligible to take part in this study, you will be enrolled in a group of at least 3 participants to begin receiving the study drugs.

The dose of the study drugs you receive will depend on when you enrolled in this study. If no intolerable side effects occur in your group, researchers will continue to enroll participants at the next dose level until either the vorinostat reaches the dose level currently used alone without stem cell transplant, or the highest tolerable dose of this drug is found. The dose that you receive will remain the same throughout this study.

You will be admitted to the hospital on Day -6.

Study Drug Administration (for all patients):

In stem cell transplant, the days before you receive your stem cells are called minus days. The day you receive the stem cells is called Day 0. The days after you receive your stem cells are called plus days.

On Day -7, -4, 0, +3 , you will take chidamide by mouth.

On Days -6, -5, -4, -3, and -2 you will receive cladribine by vein over 1/2 hours.

On Day -6, -2, you will receive gemcitabine by vein over 3 1/2 - 4 1/2 hours.

On Days -6, -5, -4, and -3, you will receive busulfan by vein over 3 hours.

On Day -1, you will rest.

On Day 0, you will receive your stem cells by vein over about 30-60 minutes.

As part of standard care, you will receive G-CSF (filgrastim) as an injection just under your skin twice a day starting on Day +5 until your blood cell levels return to normal.

Study Tests:

On Day -1, you will have an electrocardiogram (ECG) to check your heart function.

About 30-100 days after the transplant, you will have lung function tests.

About 100 days after the transplant:

Blood (about 4 teaspoons) will be drawn for routine tests. If the doctor thinks it is needed, you may have a bone marrow aspiration and biopsy to check the status of the disease.

You will have a PET/CT scan of your whole body to check the status of the disease.

Length of Study:

As part of standard care, you will remain in the hospital for about 3-4 weeks after the transplant. After you are released from the hospital, you will continue as an outpatient for infections and transplant-related complications.

You will be taken off study about 100 days after the transplant. You may be taken off study early if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

This is an investigational study. Chidamide, gemcitabine, busulfan, melphalan, and rituximab are all FDA approved and commercially available. The use of these study drugs in combination is investigational.

Up to 93 patients will take part in this study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 93
• Est. completion date: December 2021
• Est. primary completion date: December 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

1. Patients with primary refractory or recurrent diffuse large B cell lymphoma that do not qualify for treatment protocols of higher priority.

2. Relapsed patients should respond to 2nd or 3rd line salvage chemotherapy and attain at least PR before recruitment.

3. Adequate renal function, as defined by estimated serum creatinine clearance >/=50 ml/min and/or serum creatinine </= 1.8 mg/dL.

6. Adequate hepatic function, as defined by serum glutamate oxaloacetate transaminase (SGOT) and/or serum glutamate pyruvate transaminase (SGPT) </= 3 x upper limit of normal; serum bilirubin and alkaline phosphatase </= 2 x upper limit of normal.

7. Adequate pulmonary function with forced expiratory volume at one second (FEV1), forced vital capacity (FVC) and diffusing capacity of lung for carbon monoxide (DLCO) >/= 50% of expected corrected for hemoglobin.

8. Adequate cardiac function with left ventricular ejection fraction >/= 50%. No uncontrolled arrhythmias or symptomatic cardiac disease.

9. Performance status 0-1. 10. Negative Beta diffusing capacity of lung for carbon monoxide (HCG) text in a woman with child-bearing potential, defined as not post-menopausal for 12 months or no previous surgical sterilization

Exclusion Criteria:

1. Central nervous system lymphoma

2. Patients relapsed after ASCT

3. Bone marrow was involved by lymphoma

4. Patients with active hepatitis B or C(HBV DNA >/=10,000 copies/mL).

5. Active infection requiring parenteral antibiotics

6. HIV infection, unless the patient is receiving effective antiretroviral therapy with undetectable viral load and normal cluster of differentiation 4 (CD4) counts

7. Evidence of either cirrhosis or stage 3-4 liver fibrosis in patients with chronic hepatitis C or positive hepatitis C serology.

8. Patients with a cQT longer than 500 ms

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• Chidamide
30 mg oral twice weekly for 2 weeks
• Cladribine
6 mg/m2 intravenously daily for 5 days
• gemcitabine
2500 mg/m2 intravenously twice weekly for 1 week
• Busulfan
3.2 mg/kg intravenously daily for 4 days

Procedure:
• Autologous hematopoietic stem cell transplantation
autologous hematopoietic stem cells infusion after ChiCGB chemotherapy

Locations

Country	Name	City	State
China	Beijing cancer hospital	Beijing	Beijing
China	Peking university third hospital	Beijing	Beijing
China	West China Hospital of Sichuan University	Chengdu	Sichuan
China	Southwest Hospital	Chongqing	Chongqing
China	The first affiliated hospital of Chongqing medical university	Chongqing	Chongqing
China	Kunming General Hospital of Chengdu Military Area	Kunming	Yunnan
China	General Hospital of Lanzhou military command	Lanzhou	Gansu
China	Affiliated Hospital of Southwest Medical University	Nanchong	Sichuan
China	Jiangsu province hospital	Nanjing	Jiangsu
China	Rui jin hospital Shanghai jiao tong University	Shanghai	Shanghai
China	Tong Ren Hospital	Shanghai	Shanghai
China	Shan Xi Da Yi Hospital	Taiyuan	Shanxi
China	Blood diseases hospital, Chinese academy of medica	Tianjin	Tianjing
China	The first affiliated hospital of Xinjiang medical Universtiy	Ürümqi	Xinjiang
China	Tongji Hospital	Wuhan	Hubei
China	Tangdu Hospital	Xi'an	Shanxi
China	Henan cancer hospital	Zhengzhou	Henan
China	The first affiliated hospital of Zhengzhou university	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Sichuan University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event free survival		2 years
Secondary	Overall survival		2 years
Secondary	Complete remission		3 month after autologous hematopoietic stem cell transplantation
Secondary	Adverse events		2 years