Clinical trial NCT03687463: Modified Post-Transplant Cyclophosphamide Regimen for Children With Juvenile Myelomonocytic Leukemia
Official title: 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
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Hematopoietic System--Cancer
Keywords: HSCT
PT/Cy
Decitabine
JMML
Lead sponsor: Capital Research Institute of Pediatrics
Sponsor class: OTHER_GOV
First posted: 2018-09-27
Enrollment: 6
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: JMML patients are urgent to transplant, but this group of patients without suitable donor.

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: disease statue
timeFrame: one months
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
References:
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citation: 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.
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