Trial of FFP+HDMP+Rituximab for Ultra-high Risk Chronic Lymphocytic Leukemia

Chronic Lymphocytic Leukemia Clinical Trial

Official title:

Clinical Study of Chemoimmunotherapy With Fresh Frozen Plasma, High Dose Methylprednisolone and Rituximab for Ultra-high Risk Chronic Lymphocytic Leukemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01670812
• Other study ID #: JSPH-CLL-001
• Status: Recruiting
• Phase: Phase 3
• First received: August 19, 2012
• Last updated: August 19, 2012
• Start date: January 2012
• Est. completion date: June 2014

Study information

• Verified date: August 2012
• Source: The First Affiliated Hospital with Nanjing Medical University
• Contact: LEI FAN, M.D., Ph.D.
• Phone: +86 25 6813 6034
• Email: fanlei_fl[@]yahoo.com.cn
• Is FDA regulated: No
• Health authority: China: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to investigate efficacy and safety of fresh frozen plasma(FFP), high dose methylprednisolone(HDMP) and rituximab for ultra-high risk chronic lymphocytic leukemia.

Description:

Chronic lymphocytic leukemia remains incurable and particularly in ultra-high risk subgroup, and the prognosis of these patients is still dismal.

This is a phase III, multicenter perspective clinical trial of combination of fresh frozen plasma(FFP), high dose methylprednisolone(HDMP) and rituximab for ultra-high risk chronic lymphocytic leukemiaThe. The main purpose of this study is to investigate efficacy and safety of this combinated regimen in subgroup of CLL patients.

All the enrolled patients will be followed during and after the treatment period up to one year. Interim and final evaluation will be done after each cycle of treatment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: June 2014
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Aged 18-80 years old.

2. Diagnosis of chronic lymphocytic leukemia.

3. Active disease meeting at least one of the International Workshop on Chronic Lymphocytic Leukemia 2008 criteria for requiring treatment.

4. Ultra-high risk CLL(Meets at least one of the following criteria) (1)ultra high-risk genetics (17p deletion and/or TP53 mutation) (2)short PFS(<24 months)after intense immunochemotherapy treatment(i.e. FCR, FR, PCR, BR etc) (3)fludarabine-refractory

5. Understand and voluntarily sign an informed consent form, able to adhere to the study visit schedule and other protocol requirements

Exclusion Criteria:

1. Severe allergic constitution or asthma.

2. Recent myocardial infarction or hypotension.

3. ECOG performance status of = 2 at study entry.

4. Active hepatitis B(DNA >1×103/ml)

5. Severe and uncontrolled diabetes mellitus.

6. Severe and uncontrolled hypertension(BP> 150/90 mmHg after treatment).

7. Active and uncontrolled systematic infection which need treatment of antibiotics.

8. Clinical symptoms of dysfunction of central nervous system.

9. Unstable and severe gastrorrhagia and peptic ulcer.

10. Major surgery within three weeks.

11. Any potential drug abuse, medical, psychological or social conditions which may disturb this investigation and assessment.

12. In any conditions which investigator considered ineligible for this study

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

Drug:
• FFP+HDMP+Rituximab
This is a single arm, multicenter clinical trial, and the regimen including Fresh frozen plasma 400ml IV day0, Rituximab: 375 mg/m2 IV day0(after infusion of FFP), methylprednisolone 1g/m2(up to 1.5g) IV day1-day5

Locations

Country	Name	City	State
China	ChangZhou First People's Hospital	ChangZhou	Jiangsu
China	ChangZhou No.2 People's Hospital	ChangZhou	Jiangsu
China	West China School of Medicine, West China Hospital, Sichuan University	Chendu	Sichuan
China	The First affiliated Hospital of AnHui Medical Universtiy	Hefei	Anhui
China	HuaiAn First People's Hospital	HuaiAn	Jiangsu
China	Shandong Provincial Hospital	Jinan	Shandong
China	JiangSu Province Hospital	NanJing	Jiangsu
China	JiangSu Province Hospital of TCM	Nanjing	Jiangsu
China	NanJing First People's Hospital	NanJing	Jiangsu
China	TongJi Medical University affiliated TongJi Hospital	Shanghai	Shanghai
China	Institute of Hematology & Blood Diseases Hospital	TianJin	Tianjin
China	TongJi Hospital	Wuhan	Hubei
China	WuXi People's Hospital	WuXi	Jiangsu
China	ZhenJiang First People's Hospital	ZhenJiang	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
The First Affiliated Hospital with Nanjing Medical University

Country where clinical trial is conducted

China, 

References & Publications (4)

Dungarwalla M, Evans SO, Riley U, Catovsky D, Dearden CE, Matutes E. High dose methylprednisolone and rituximab is an effective therapy in advanced refractory chronic lymphocytic leukemia resistant to fludarabine therapy. Haematologica. 2008 Mar;93(3):475-6. doi: 10.3324/haematol.11903. — View Citation

Klepfish A, Gilles L, Ioannis K, Rachmilewitz EA, Schattner A. Enhancing the action of rituximab in chronic lymphocytic leukemia by adding fresh frozen plasma: complement/rituximab interactions & clinical results in refractory CLL. Ann N Y Acad Sci. 2009 Sep;1173:865-73. doi: 10.1111/j.1749-6632.2009.04803.x. Erratum in: Ann N Y Acad Sci. 2010 Aug;1204:198. Eliezer, Rachmilewitz [corrected to Rachmilewitz, Eliezer A]; Ami, Schattner [corrected to Schattner, Ami]. — View Citation

Xu W, Miao KR, Hong M, Zhu DX, Fang C, Dong HJ, Wang DM, Cao X, Li JY. High-dose methylprednisolone can induce remissions in patients with fludarabine-refractory chronic lymphocytic leukaemia. Eur J Cancer. 2010 Aug;46(12):2145-9. doi: 10.1016/j.ejca.2010.04.021. Epub 2010 Jun 4. — View Citation

Xu W, Miao KR, Zhu DX, Fang C, Zhu HY, Dong HJ, Wang DM, Wu YJ, Qiao C, Li JY. Enhancing the action of rituximab by adding fresh frozen plasma for the treatment of fludarabine refractory chronic lymphocytic leukemia. Int J Cancer. 2011 May 1;128(9):2192-201. doi: 10.1002/ijc.25560. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	overall response rate	overall response rate after treated by FFP+HDMP+Rituximab regimen	one year	No
Secondary	progression free survival	progression free survival after treatment of FFP+HDMP+Rituximab for ultra-high risk CLL patients.	one year	No
Secondary	overall survival	overall survival after treatment of FFP+HDMP+Rituximab for ultra-high risk CLL patients	one year	No
Secondary	Number of Participants with Adverse Events	Number of Participants with Adverse Events, and evaluated standard is according to common terminology criteria adverse events(CTCAE) version 4.0	up to 30 days after last dose of treatment	Yes