- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03687463
Modified Post-Transplant Cyclophosphamide Regimen for Children With Juvenile Myelomonocytic Leukemia
September 30, 2018 updated by: Yan Yue, Capital Research Institute of Pediatrics
Modified Post-Transplant Cyclophosphamide Combined With DCAG as a Bridge Followed by Busulfan, Fludarabine and Melphalan Based Conditioning Regimen for Children With Juvenile Myelomonocytic Leukemia
Hematopoietic stem cell transplantation (HSCT) is the only curative option for most of juvenile myelomonocytic leukemia (JMML).
However, relapse after HSCT severely influence the long-term overall survival (OS).
Researches demonstrate that these malignant myeloid disorders is a particular responsiveness to epigenetic therapy with the DNA-hypomethylating agents decitabine.
However, hypomethylating therapy does not eradicate the malignant clone in JMML and an emerging concept with intriguing potential is the combination of hypomethylating therapy and HSCT.
Graft-versus-host disease (GVHD) is major complication after HSCT as a threshold of the quality of patient life.
Many data indicate that post -transplant cyclophosphamide (PT/Cy) is an effective method to control the occurrence of GVHD.
Study Overview
Detailed Description
Hematopoietic stem cell transplantation (HSCT) is the only curative option for most of juvenile myelomonocytic leukemia (JMML).
However, persistent disease statute and relapse after HSCT severely influence the long-term overall survival (OS).
Researches demonstrate that JMML is an aggressive myeloproliferative neoplasm occurring in young children.
The common denominator of these malignant myeloid disorders is a particular responsiveness to epigenetic therapy with the DNA-hypomethylating agents 5-azacytidine (azacitidine) or decitabine.
However, hypomethylating therapy does not eradicate the malignant clone in JMML and an emerging concept with intriguing potential is the combination of hypomethylating therapy and HSCT.
Graft-versus-host disease (GVHD) is severe complication after HSCT.
Post -transplant cyclophosphamide (PT/Cy) is an effective method to control the occurrence of GVHD.
Based on these encouraging results, investigators launched a noval method for patients diagnosed as JMML and treated in our institution.
They modified PT/Cy conditioning regimens.
Patients all subsequently received modified DCAG regimen as the induction chemotherapy including decitabine of 20 mg/m2 intravenously over 4 h for five consecutive days (Day -15 to -11) followed by cytarabine of 10 mg/m2 q12 h for 7 days (Day -15 to -9), aclarubicin of 10 mg/day for 4 days (Day -12 to -9), and G-CSF 5µg/kg per day for priming until white blood count was >20 x109/L and immediately followed by myeloablative conditioning regimen (MAC) consisted with thymoglobulin (2.5mg/kg/day) which was administered for 3 days (Day -8 to -6), iv Bu (4 mg/kg in divided doses daily for 4 days) on days -5, -4, -3, and -2, iv Flu (30 mg/m2 once daily for 4 days, total dose 120 mg/m2) on days -5, -4, -3, and -2 and iv Melphlan (70 mg/m2 once daily for 3 days, total dose210 mg/m2) was performed on days -4 and -2.
Study Type
Observational
Enrollment (Actual)
6
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
1 year to 18 years (Child, Adult)
Accepts Healthy Volunteers
N/A
Genders Eligible for Study
All
Sampling Method
Probability Sample
Study Population
JMML patients are urgent to transplant, but this group of patients without suitable donor.
Description
Inclusion Criteria:
- JMML patients diagnosed in our center and with the indications of transplant without the suitable donor.
Exclusion Criteria:
- JMML patients do not need to transplant.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
disease statue
Time Frame: one months
|
Disease status can be measured by test the of (minimal residual disease) MRD, MRD<0,01% as negative.
The quantitative of gene mutation is "0" as negative.
|
one months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Dvorak CC, Satwani P, Stieglitz E, Cairo MS, Dang H, Pei Q, Gao Y, Wall D, Mazor T, Olshen AB, Parker JS, Kahwash S, Hirsch B, Raimondi S, Patel N, Skeens M, Cooper T, Mehta PA, Grupp SA, Loh ML. Disease burden and conditioning regimens in ASCT1221, a randomized phase II trial in children with juvenile myelomonocytic leukemia: A Children's Oncology Group study. Pediatr Blood Cancer. 2018 Jul;65(7):e27034. doi: 10.1002/pbc.27034. Epub 2018 Mar 12.
- Zaucha-Prazmo A, Gozdzik J, Debski R, Drabko K, Sadurska E, Kowalczyk JR. Transplant-related mortality and survival in children with malignancies treated with allogeneic hematopoietic stem cell transplantation. A multicenter analysis. Pediatr Transplant. 2018 May;22(3):e13158. doi: 10.1111/petr.13158. Epub 2018 Feb 3.
- Flotho C, Sommer S, Lubbert M. DNA-hypomethylating agents as epigenetic therapy before and after allogeneic hematopoietic stem cell transplantation in myelodysplastic syndromes and juvenile myelomonocytic leukemia. Semin Cancer Biol. 2018 Aug;51:68-79. doi: 10.1016/j.semcancer.2017.10.011. Epub 2017 Nov 9.
- Locatelli F, Niemeyer CM. How I treat juvenile myelomonocytic leukemia. Blood. 2015 Feb 12;125(7):1083-90. doi: 10.1182/blood-2014-08-550483. Epub 2015 Jan 6.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
April 10, 2015
Primary Completion (Actual)
July 10, 2018
Study Completion (Anticipated)
April 10, 2020
Study Registration Dates
First Submitted
September 25, 2018
First Submitted That Met QC Criteria
September 25, 2018
First Posted (Actual)
September 27, 2018
Study Record Updates
Last Update Posted (Actual)
October 2, 2018
Last Update Submitted That Met QC Criteria
September 30, 2018
Last Verified
September 1, 2018
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Bone Marrow Diseases
- Hematologic Diseases
- Myelodysplastic-Myeloproliferative Diseases
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myelomonocytic, Juvenile
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Decitabine
Other Study ID Numbers
- CIP-2015-JMML
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Undecided
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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