Clinical trial NCT01670812: Trial of FFP+HDMP+Rituximab for Ultra-high Risk Chronic Lymphocytic Leukemia
Official title: Clinical Study of Chemoimmunotherapy With Fresh Frozen Plasma, High Dose Methylprednisolone and Rituximab for Ultra-high Risk Chronic Lymphocytic Leukemia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Chronic Lymphocytic Leukemia
Keywords: chronic lymphocytic leukemia
ultra-high risk
fresh frozen plasma
methylprednisolone
rituximab
Lead sponsor: The First Affiliated Hospital with Nanjing Medical University
Sponsor class: OTHER
First posted: 2012-08-22
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: overall response rate
timeFrame: one year
Secondary outcomes:
measure: progression free survival
timeFrame: one year
measure: overall survival
timeFrame: one year
measure: Number of Participants with Adverse Events
timeFrame: up to 30 days after last dose of treatment
Other outcomes:
Locations:
city: Hefei
country: China
facility: The First affiliated Hospital of AnHui Medical Universtiy
state: Anhui
city: Wuhan
country: China
facility: TongJi Hospital
state: Hubei
city: ChangZhou
country: China
facility: ChangZhou First People's Hospital
state: Jiangsu
city: ChangZhou
country: China
facility: ChangZhou No.2 People's Hospital
state: Jiangsu
city: HuaiAn
country: China
facility: HuaiAn First People's Hospital
state: Jiangsu
city: NanJing
country: China
facility: NanJing First People's Hospital
state: Jiangsu
city: NanJing
country: China
facility: JiangSu Province Hospital
state: Jiangsu
city: Nanjing
country: China
facility: JiangSu Province Hospital of TCM
state: Jiangsu
city: WuXi
country: China
facility: WuXi People's Hospital
state: Jiangsu
city: ZhenJiang
country: China
facility: ZhenJiang First People's Hospital
state: Jiangsu
city: Jinan
country: China
facility: Shandong Provincial Hospital
state: Shandong
city: Shanghai
country: China
facility: TongJi Medical University affiliated TongJi Hospital
state: Shanghai
city: Chendu
country: China
facility: West China School of Medicine, West China Hospital, Sichuan University
state: Sichuan
city: TianJin
country: China
facility: Institute of Hematology & Blood Diseases Hospital
state: Tianjin
Study officials:
affiliation: The First Affiliated Hospital with Nanjing Medical University
name: Wei Xu, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
citation: 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.
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.