Hematopoietic System--CancerNCT03687463
Modified Post-Transplant Cyclophosphamide Regimen for Children With Juvenile Myelomonocytic Leukemia
An observational study of Hematopoietic System--Cancer, run by Capital Research Institute of Pediatrics.
Trial 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). Read more about this study
- Who is it for?
- Ages 1 year to 18 years
- Conditions the study is for
- Hematopoietic System--Cancer
- What is being tested?
- Decitabine
- Type of treatment
- Injection or infusion
- How many people
- 6 participants
- Where
- No sites listed yet
- Study dates
- 10 Apr 2015to 10 Apr 2020
- How long will I take part?
- 5 Years
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 18 years
- All sexes
- Child, Adult
Study population: JMML patients are urgent to transplant, but this group of patients without suitable donor.
Who may be able to join
- JMML patients diagnosed in our center and with the indications of transplant without the suitable donor.
Who cannot join
- JMML patients do not need to transplant.
About this study
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
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.
Read the 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
- Being tested
- Decitabine
- Keywords
- HSCT, PT/Cy, Decitabine, JMML
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DecitabineDrug
Also called Dacogen
Decitabine for injection
What is being measured
The primary outcome is the main question the study is designed to answer.
disease statue
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.
Measured: one months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Sep 2018
- Study start10 Apr 2015
- Primary completion10 Jul 2018
- Study completion10 Apr 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Hematopoietic System--CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 6 participants (actual)
- Target duration
- 5 Years
Sponsor and investigators
- Lead sponsor
- Capital Research Institute of Pediatrics
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Yan Yue, Capital Research Institute of Pediatrics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03687463
- Sponsor's protocol ID
- CIP-2015-JMML
- Status last verified
- Sep 2018
- First submitted
- 25 Sep 2018
- Last updated
- 2 Oct 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
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.
PubMed 29528181Zaucha-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.
PubMed 29396905Flotho 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.
PubMed 29129488Locatelli 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.
PubMed 25564399
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03687463
- Acronym / sponsor ID
- CIP-2015-JMML
- Conditions
- Hematopoietic System--Cancer
- Keywords
- HSCT, PT/Cy, Decitabine, JMML
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Capital Research Institute of PediatricsOther government
- Study start
- 10 Apr 2015 (actual)
- Primary completion
- 10 Jul 2018 (actual)
- Study completion
- 10 Apr 2020 (estimated)
- First posted
- 27 Sep 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 5 Years
Who may qualify
- Ages
- 1 year to 18 years
- Sex
- All
- Age groups
- Child, Adult
- Study population
- JMML patients are urgent to transplant, but this group of patients without suitable donor.
Key inclusion criteria (1 listed)
- JMML patients diagnosed in our center and with the indications of transplant without the suitable donor.
Key exclusion criteria (1 listed)
- JMML patients do not need to transplant.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DecitabineAlso: DacogenDecitabine for injection | Drug | – |
Primary outcome
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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2018.
- Results publication: PubMed 29528181Dvorak 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.
- Results publication: PubMed 29396905Zaucha-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.
- Results publication: PubMed 29129488Flotho 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.
- Results publication: PubMed 25564399Locatelli 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
An observational study of Hematopoietic System--Cancer, run by Capital Research Institute of Pediatrics.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 2 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
disease statue (time frame: one months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03687463, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2018.