Modified Post-Transplant Cyclophosphamide Regimen for Children With Juvenile Myelomonocytic Leukemia

NCT ID: NCT03687463

Last Updated: 2018-10-02

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 6 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2015-04-10
• Study Completion Date: 2020-04-10

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.

Conditions

Hematopoietic System--Cancer

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Interventions

Decitabine

Decitabine for injection

Intervention Type: DRUG

Other Intervention Names

Dacogen

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.

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Capital Research Institute of Pediatrics

OTHER_GOV

Sponsor Role: lead

Responsible Party

Yan Yue

Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

References

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.

Reference Type: RESULT

PMID: 29528181 (View on PubMed)

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.

Reference Type: RESULT

PMID: 29396905 (View on PubMed)

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.

Reference Type: RESULT

PMID: 29129488 (View on PubMed)

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.

Reference Type: RESULT

PMID: 25564399 (View on PubMed)

Other Identifiers

CIP-2015-JMML

Identifier Type: -

Identifier Source: org_study_id