Condition category
Cancer
Date applied
11/01/2016
Date assigned
14/01/2016
Last edited
14/01/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Chronic myeloid leukemia (CML) is a cancer in which the bone marrow makes too many white blood cells. These cells are called granulocytes or leukemia cells; they are abnormal and do not become healthy white blood cells. The leukemia cells can build up in the blood and bone marrow so there is less room for healthy white blood cells, red blood cells, and platelets. When this happens, infection, anemia, or easy bleeding may occur. Most people with CML have a gene mutation (BCR-ABL gene) called the Philadelphia chromosome. The goal of treatment is to eliminate the blood cells that contain the abnormal BCR-ABL gene. For most patients, it's not possible to get rid of all leukemia cells, but treatment can help achieve a long-term remission of the disease. Current treatment choices include: targeted drugs like Imatinib (Gleevec), blood stem cell transplant, chemotherapy, and biological therapy. Each treatment option has its own advantages and disadvantages. The prognosis for patients with advanced CML is usually poor, as the treatments available to these patients often do not work. Hydroxyurea is a type of chemotherapy drug called an antimetabolite. Antimetaboloites work by stopping cells making and repairing DNA; cancer cells need to do both these things in order grow and multiply. However, hydroxyurea may also cause the number of bone marrow blood cells to fall to a very low number. This increases the risk of serious bleeding and infection. It may also cause other cancers, including skin cancer. In light of how well hydroxyurea works and its side effects, it may be possible for patients to not take it for as long and still get the same amount of benefit from the treatment. Imatinib is a type of biological therapy called a tyrosine kinase inhibitor. Tyrosine kinases are proteins that act as chemical messengers that cells use to signal to each other to grow. Imatinib works by blocking certain types of tyrosine kinases. This stops the cancer cells from growing. The dose (amount) of Imatinib given to CML patients is usually high and given for the rest of the patients life. Side effects can include swelling or puffiness of the skin, nausea, muscle cramps, rash, fatigue, diarrhea, and skin rashes. In addition to this, patients may not respond or become resistant to the drug. This study looks at treating CML patients with hydroxyurea for a very short period of time (usually 3 to 7 days) to stop the growth of leukemia cells and then a much reduced dose of Imatinib. It is hoped that the combined function of these two drugs will significantly reduce the dose that patients need to take, improve the patients quality of life, improve both liver and kidney function, reduce drug side effects and decrease the risk of drug resistance.

Who can participate?
Patients diagnosed with CML.

What does the study involve?
All participants are treated with hydroxyurea combined with imatinib. Samples of blood and bone marrow are taken and tested every 6 months to test for progression of the disease. All participants are given the treatment for the rest of their lives and are followed up every 6 months for at least 5 years or until their death.

What are the possible benefits and risks of participating?
Not provided at time of registration

Where is the study run from?
First Affiliated Hospital of Harbin Medical University (China)

When is the study starting and how long is it expected to run for?
May 2003 to December 2024

Who is funding the study?
National Natural Science Foundation of China

Who is the main contact?
Professor Jin Zhou
zhoujin1111@126.com

Trial website

Contact information

Type

Scientific

Primary contact

Prof Jin Zhou

ORCID ID

Contact details

Department of Hematology
First Affiliated Hospital
Harbin Medical University
Harbin
150001
China
+86 (0) 451 53641824
zhoujin1111@126.com

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

2004-08-CHN

Study information

Scientific title

Prospective study on an effective treatment for chronic myeloid leukemia with hydroxyurea and imatinib

Acronym

Study hypothesis

Short period use of hydroxyurea combined with low-dose imatinib function cooperatively will improve the clinical outcome for chronic myeloid leukemia (CML) patients during treatment at accelerated phase and blastic phase.

Ethics approval

Harbin Medical University Ethics Committee, 3/20/2002, ref: HM011502.

Study design

Interventional

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

The patient information sheets are available at the First Affiliated Hospital at Harbin Medical University

Condition

Chronic myeloid leukemia (CML)

Intervention

Chronic myeloid leukemia (CML) patients who give written consent are enrolled. First stage is to control leukocytosis, which includes daily oral hydroxyurea 1-3 g for 3-7 days. A total of three treatment cycles are repeated with 2-week intervals until leukocytosis is well controlled. For CML cell elimination therapy, oral imatinib of 200-600 mg/day is maintained for life. Blood and bone marrow cell study, biopsy, and cytogenetics are tested once every 6 months. The total duration of treatment is life time, and follow-up for all treatment arms is from diagnosis, then once every 6 months, until death or 5 years and beyond.

Intervention type

Mixed

Phase

Drug names

Primary outcome measures

1. Overall survival (OS): It is calculated from the start of the treatment until the last follow up or death
2. Disease-free survival (DFS): It is calculated as time of MR until the last follow-up, relapse, death from any cause, or occurrence of severe side effects.

Assessed with an interval of every 6 months clinical follow up.

Secondary outcome measures

1. Complete hematologic remission (CHR) ―Normal complete blood count and normal physical examination
2. Complete cytogenetic remission (CCR) ―Normal chromosome examination with no Ph positive cells detectable on metaphase cytogenetic of bone marrow with 20-25 cells analyzed
3. Molecular remission (MR) ―Negative RT-PCR evidence of the BCR-ABL mRNA

All measured with clinical examination, peripheral blood test, bone marrow cell count, cytogenetic study, FISH, and QRT-PCR at an interval of 3 months

4. Quality of life (QOL) – Using “Professional Quality of Life Scale” at each 6 month clinical follow up visit

Overall trial start date

01/05/2003

Overall trial end date

31/12/2024

Reason abandoned

Eligibility

Participant inclusion criteria

1. Any age CML patients at different disease stages, who are responsive or non-responsive to conventional treatments are all included in this trial
2. Patients agreed to receive the treatment

Participant type

Patient

Age group

All

Gender

Both

Target number of participants

2000

Participant exclusion criteria

1. Previous history of severe cardiovascular disease (coronary arterial disease, stroke, etc.)
2. Severe chronic disease with poor prognosis (liver disease, kidney disease, etc.)
3. Illegal drug use or chronic alcoholism
4. Physical limitations, mental or intellectual disabilities
5. Any condition that may affect the development of this trial

Recruitment start date

01/05/2003

Recruitment end date

30/01/2024

Locations

Countries of recruitment

China

Trial participating centre

First Affiliated Hospital of Harbin Medical University
Department of Hematology First Affiliated Hospital Harbin Medical University
Harbin
150001
China

Sponsor information

Organisation

Heilongjiang Institute for Hematology and Oncology Research

Sponsor details

c/o Zhuo Zhang
100 Longjiang St.
Bldg 5
Harbin
150001
China
+86 (0) 451 53670428
zhuobenz0@gmail.com

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Research organisation

Funder name

National Natural Science Foundation of China

Alternative name(s)

National Science Foundation of China, Natural Science Foundation of China, NSFC

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

China

Funder name

China 863 Projects Foundation, No. 2012AA020903 (China)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Data are collected and analyzed on a yearly basis, from which two articles are expected to be published in English in peer-reviewed SCI journal(s) in 2016 and 2026.

Intention to publish date

Participant level data

Available on request

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes