High Risk Acute Myeloid LeukemiaPhase 3NCT03384225
CBA Versus FBA Conditioning Followed by Haploidentical Allogeneic HSCT in Treatment of High Risk and Refractory AML
A Phase 3 study testing Cladribine, Fludarabine and Busulfan in people with High Risk Acute Myeloid Leukemia and Allogeneic Hematopoeitic Stem Cell Transplantation, run by Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine at 1 site in China.
Trial summary
Aim: To evaluated if cladribine based conditioning (CBA) could decrease relapse after haploidentical allogeneic HSCT in high risk and refractory AML patients as compared with fludarabine based conditioning regimen(FBA). Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- High Risk Acute Myeloid Leukemia, Allogeneic Hematopoeitic Stem Cell Transplantation
- What is being tested?
- Cladribine, Fludarabine and Busulfan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteChina
- Study dates
- 1 Aug 2016to 31 Jul 2022
- Phase
- Phase 3
- 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 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Diagnosis of AML confirmed by bone marrow cell morphology, immunology, cytogenetics and molecular biology (MICM). Blast crisis of chronic myeloid leukemia (CML) and AML transferred from myelodysplastic syndrome(MDS) or other diseases are also included.
- AML with high risk cytogenetic abnormals, such as FLT3- ITD, et al.
- Patients fulfilled at least one of the following criteria defining refractory AML:(1) primary induction failure (PIF) after 2 or more cycles of chemotherapy; (2) first early relapse after a remission duration of fewer than 12 months and refractory to salvage combination chemotherapy; (3) second or subsequent relapse .
- Have no HLA matched siblings or unrelated donors, but have haploidentical donor. The donor must match the health conditions of hematopoietic stem cell donation (criteria of China Marrow Donor Program) and be willing to donate.
- Performance status score no more than 2 (ECOG criteria).
- Adequate organ function as defined by the following criteria:ALT, AST and total serum bilirubin <2×ULN (upper limit of normal), Serum creatinine and BUN <1.25×ULN.
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- Adequate cardiac function without acute myocardial infarction, arrhythmia or atrioventricular block, heart failure, active rheumatic heart disease and cardiac dilatation.
- Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment.
- Willingness and ability to comly with scheduled visits, treatment plans, laboratory tests, and other study procedures.
Who cannot join
- Presence of any condition inappropriate for HSCT.
- Presence of any fatal disease, including respiratory failure, heart failure, liver or kidney function failure et al.
- Have no suitable donor.
- Pregnancy or breast feeding.
- Current treatment on another clinical trail.
- Any other condition the investigator judged the patient inappropriate for entry into this study
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Shanghai general hospital, Shanghai Jiaotong university school of medicine
Shanghai, Shanghai Municipality, 200080
Xingpeng Wang, M.D.,Ph. D., 86-21-63069298, sfph_edu2@163.com
Yanhong Zhu, 86-21-63240090 ext. 6213, sfph_edu2@shumu.edu.cn
About this study
Aim: To evaluated if cladribine based conditioning (CBA) could decrease relapse after haploidentical allogeneic HSCT in high risk and refractory AML patients as compared with fludarabine based conditioning regimen(FBA).
Study design: open-labed, prospective, multicenter, randomized control study Number of subjects: 60 each group
Treatment:
CBA group: CBA as HSCT conditioning which including cladribine 5mg/m2 day
-6 to day -2 , busulfan(iv) 3.2mg/kg day-6 to day -3 and cytarabine 2g/m2 day-6 to day -2. FBA group: FBA as HSCT conditioning which including fludarabine 30mg/m2 day -6 to day -2, busulfan(iv) 3.2mg/kg day-6 to day -3 and cytarabine 2g/m2 day-6 to day -2.
Read the detailed description
Relapse is still the main reason of death for patients with acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (HSCT), especially for those with high risk and refractory disease. Cladribine and fludarabine are both purine analogs used in treatment of AML. Two studies by the Polish Adult Leukemia Group (PALG) demonstrated that the addition of cladribine to DA (DAC) was associated with an increased complete remission (CR) rate and prolonged overall survival (OS) in the general AML population, with the most prominent effect in patients with unfavorable cytogenetics. Therefore we presume cladribine may more effective in eliminating leukemic cells so that reduce relapse after HSCT. Haploidentical HSCT was the main option for those without HLA matched donors and the number of haploidentical transplants has covered over fifty percent of all allogeneic transplants in China. We designed this study to evaluated if cladribine based conditioning (CBA) could decrease relapse after haploidentical HSCT in high risk and refractory AML patients as compared with fludarabine based conditioning regimen(FBA).
Eligible patients in this study should between 18 to 60 years old with confirmed AML and fulfilled at least one criteria defining high risk or refractory disease.Patients have no HLA matched sibling or unrelated donors but have haploidentical donor. Patients will be excluded if they present any contraindication for HSCT, including respiratory failure, heart failure, liver or kidney function failure et al.
To evaluate if CBA could decrease relapse after haploidentical HSCT in high risk and refractory AML patients as compared with FBA, 120 eligible patients will be randomized to two groups, the CBA group and the FBA group. Patients in the CBA group receive conditioning including cladribine 5mg/m2 day -6 to day -2 , busulfan(iv) 3.2mg/kg day-6 to day -3 and cytarabine 2g/m2 day-6 to day -2. While patients in the FBA group receive conditioning including fludarabine 30mg/m2 day -6 to day -2 , busulfan(iv) 3.2mg/kg day-6 to day-3 and cytarabine 2g/m2 day-6 to day -2. Graft versus host disease(GVHD) prophylactic regimen include ATG 2.5mg/kg d-4 to d-1, cyclosporine A and short term MTX.
Patients will be followed up for 2 years and the primary end point is the cumulative relapse rate at 2 years. The second end points of the study include the overall survival, disease free survival and non-relapse mortality at 2 years.
- Being tested
- Cladribine, Fludarabine, Busulfan, Cytarabine
- Keywords
- cladribine, fludarabine, relapse
- Medical subject headings
- Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CladribineDrug
Also called chlorodeoxyadenosine
FludarabineDrug
BusulfanDrug
Also called busulphan
CytarabineDrug
Also called cytosine arabinoside
| Study group | Role | What they receive |
|---|---|---|
| CBA group | Experimental | CBA as HSCT conditioning:
cladribine 5mg/m2 day -6 to day -2 busulfan(iv) 3.2mg/kg day-6 to day -3 cytarabine 2g/m2 day-6 to day -2 Receives: Drug: Cladribine; Drug: Busulfan; Drug: Cytarabine |
| FBA group | Active comparator | FBA as HSCT conditioning:
fludarabine 30mg/m2 day -6 to day -2 busulfan(iv) 3.2mg/kg day-6 to day -3 cytarabine 2g/m2 day-6 to day -2 Receives: Drug: Fludarabine; Drug: Busulfan; Drug: Cytarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
cumulative relapse rate at 2 year
The percentage of all patients who are relapsed within 2 years after allogeneic HSCT.
Measured: 2 years
Secondary outcomes (4)
overall survival at 2 year
The percentage of all patients who are still alive 2 years after allogeneic HSCT.
Measured: 2 years
disease free survival at 2year
The percentage of all patients who are leukemia free 2 years after allogeneic HSCT.
Measured: 2 years
non-relapse mortality at 2year
The percentage of patients who are dead within 2 years of all reasons except relapse.
Measured: 2 years
non-relapse mortality at 100days
The percentage of patients who are dead within 100days of all reasons except relapse.
Measured: 100 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Dec 2017
- Study start1 Aug 2016
- Primary completion31 Jul 2022 (estimated)
- Study completion31 Jul 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for High Risk Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by Shanghai General Hospital, Shanghai Jiao Tong University School of MedicineThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Parallel Assignment open labled randomized controlled study
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Changhai Hospital, Xiangya Hospital of Central South University, Tongji Hospital, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Chengdu PLA General Hospital, Tang-Du Hospital, Fujian Medical University Union Hospital
- Responsible party
- Principal investigator, Chun Wang, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
- Investigators
- Chun Wang, M.D.,Ph. D., Study chair, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03384225
- Sponsor's protocol ID
- 2016-221
- Status last verified
- Oct 2021
- First submitted
- 5 Nov 2017
- Last updated
- 12 Oct 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Holowiecki J, Grosicki S, Robak T, Kyrcz-Krzemien S, Giebel S, Hellmann A, Skotnicki A, Jedrzejczak WW, Konopka L, Kuliczkowski K, Zdziarska B, Dmoszynska A, Marianska B, Pluta A, Zawilska K, Komarnicki M, Kloczko J, Sulek K, Haus O, Stella-Holowiecka B, Baran W, Jakubas B, Paluszewska M, Wierzbowska A, Kielbinski M, Jagoda K; Polish Adult Leukemia Group (PALG). Addition of cladribine to daunorubicin and cytarabine increases complete remission rate after a single course of induction treatment in acute myeloid leukemia. Multicenter, phase III study. Leukemia. 2004 May;18(5):989-97. doi: 10.1038/sj.leu.2403336.
PubMed 14999298Holowiecki J, Grosicki S, Giebel S, Robak T, Kyrcz-Krzemien S, Kuliczkowski K, Skotnicki AB, Hellmann A, Sulek K, Dmoszynska A, Kloczko J, Jedrzejczak WW, Zdziarska B, Warzocha K, Zawilska K, Komarnicki M, Kielbinski M, Piatkowska-Jakubas B, Wierzbowska A, Wach M, Haus O. Cladribine, but not fludarabine, added to daunorubicin and cytarabine during induction prolongs survival of patients with acute myeloid leukemia: a multicenter, randomized phase III study. J Clin Oncol. 2012 Jul 10;30(20):2441-8. doi: 10.1200/JCO.2011.37.1286. Epub 2012 Apr 16.
PubMed 22508825
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CBA Versus FBA Conditioning Followed by Haploidentical Allogeneic HSCT in Treatment of High Risk and Refractory AML
- ClinicalTrials.gov ID
- NCT03384225
- Acronym / sponsor ID
- 2016-221
- Keywords
- cladribine, fludarabine, relapse
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Shanghai General Hospital, Shanghai Jiao Tong University School of MedicineUniversity, hospital or other
- Collaborators
- Changhai Hospital, Xiangya Hospital of Central South University, Tongji Hospital, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Chengdu PLA General Hospital, Tang-Du Hospital, Fujian Medical University Union Hospital
- Study start
- 1 Aug 2016 (actual)
- Primary completion
- 31 Jul 2022 (estimated)
- Study completion
- 31 Jul 2022 (estimated)
- First posted
- 27 Dec 2017 (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.
Aim: To evaluated if cladribine based conditioning (CBA) could decrease relapse after haploidentical allogeneic HSCT in high risk and refractory AML patients as compared with fludarabine based conditioning regimen(FBA).
Study design: open-labed, prospective, multicenter, randomized control study Number of subjects: 60 each group
Treatment:
CBA group: CBA as HSCT conditioning which including cladribine 5mg/m2 day
-6 to day -2 , busulfan(iv) 3.2mg/kg day-6 to day -3 and cytarabine 2g/m2 day-6 to day -2. FBA group: FBA as HSCT conditioning which including fludarabine 30mg/m2 day -6 to day -2, busulfan(iv) 3.2mg/kg day-6 to day -3 and cytarabine 2g/m2 day-6 to day -2.
Detailed description
Relapse is still the main reason of death for patients with acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (HSCT), especially for those with high risk and refractory disease. Cladribine and fludarabine are both purine analogs used in treatment of AML. Two studies by the Polish Adult Leukemia Group (PALG) demonstrated that the addition of cladribine to DA (DAC) was associated with an increased complete remission (CR) rate and prolonged overall survival (OS) in the general AML population, with the most prominent effect in patients with unfavorable cytogenetics. Therefore we presume cladribine may more effective in eliminating leukemic cells so that reduce relapse after HSCT. Haploidentical HSCT was the main option for those without HLA matched donors and the number of haploidentical transplants has covered over fifty percent of all allogeneic transplants in China. We designed this study to evaluated if cladribine based conditioning (CBA) could decrease relapse after haploidentical HSCT in high risk and refractory AML patients as compared with fludarabine based conditioning regimen(FBA).
Eligible patients in this study should between 18 to 60 years old with confirmed AML and fulfilled at least one criteria defining high risk or refractory disease.Patients have no HLA matched sibling or unrelated donors but have haploidentical donor. Patients will be excluded if they present any contraindication for HSCT, including respiratory failure, heart failure, liver or kidney function failure et al.
To evaluate if CBA could decrease relapse after haploidentical HSCT in high risk and refractory AML patients as compared with FBA, 120 eligible patients will be randomized to two groups, the CBA group and the FBA group. Patients in the CBA group receive conditioning including cladribine 5mg/m2 day -6 to day -2 , busulfan(iv) 3.2mg/kg day-6 to day -3 and cytarabine 2g/m2 day-6 to day -2. While patients in the FBA group receive conditioning including fludarabine 30mg/m2 day -6 to day -2 , busulfan(iv) 3.2mg/kg day-6 to day-3 and cytarabine 2g/m2 day-6 to day -2. Graft versus host disease(GVHD) prophylactic regimen include ATG 2.5mg/kg d-4 to d-1, cyclosporine A and short term MTX.
Patients will be followed up for 2 years and the primary end point is the cumulative relapse rate at 2 years. The second end points of the study include the overall survival, disease free survival and non-relapse mortality at 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Parallel Assignment open labled randomized controlled study
| Arm | Type | Receives |
|---|---|---|
| CBA group | Experimental | Drug: Cladribine, Drug: Busulfan, Drug: CytarabineCBA as HSCT conditioning: cladribine 5mg/m2 day -6 to day -2 busulfan(iv) 3.2mg/kg day-6 to day -3 cytarabine 2g/m2 day-6 to day -2 |
| FBA group | Active comparator | Drug: Fludarabine, Drug: Busulfan, Drug: CytarabineFBA as HSCT conditioning: fludarabine 30mg/m2 day -6 to day -2 busulfan(iv) 3.2mg/kg day-6 to day -3 cytarabine 2g/m2 day-6 to day -2 |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Diagnosis of AML confirmed by bone marrow cell morphology, immunology, cytogenetics and molecular biology (MICM). Blast crisis of chronic myeloid leukemia (CML) and AML transferred from myelodysplastic syndrome(MDS) or other diseases are also included.
- AML with high risk cytogenetic abnormals, such as FLT3- ITD, et al.
- Patients fulfilled at least one of the following criteria defining refractory AML:(1) primary induction failure (PIF) after 2 or more cycles of chemotherapy; (2) first early relapse after a remission duration of fewer than 12 months and refractory to salvage combination chemotherapy; (3) second or subsequent relapse .
- Have no HLA matched siblings or unrelated donors, but have haploidentical donor. The donor must match the health conditions of hematopoietic stem cell donation (criteria of China Marrow Donor Program) and be willing to donate.
- Performance status score no more than 2 (ECOG criteria).
Key exclusion criteria (6 listed)
- Presence of any condition inappropriate for HSCT.
- Presence of any fatal disease, including respiratory failure, heart failure, liver or kidney function failure et al.
- Have no suitable donor.
- Pregnancy or breast feeding.
- Current treatment on another clinical trail.
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 |
|---|---|---|
| CladribineAlso: chlorodeoxyadenosine | Drug | CBA group |
| Fludarabine | Drug | FBA group |
| BusulfanAlso: busulphan | Drug | CBA group, FBA group |
| CytarabineAlso: cytosine arabinoside | Drug | CBA group, FBA group |
Primary outcome
cumulative relapse rate at 2 year
Time frame: 2 years
The percentage of all patients who are relapsed within 2 years after allogeneic HSCT.
4 secondary outcomes
overall survival at 2 year
Time frame: 2 years
disease free survival at 2year
Time frame: 2 years
non-relapse mortality at 2year
Time frame: 2 years
non-relapse mortality at 100days
Time frame: 100 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2021.
- Background: PubMed 14999298Holowiecki J, Grosicki S, Robak T, Kyrcz-Krzemien S, Giebel S, Hellmann A, Skotnicki A, Jedrzejczak WW, Konopka L, Kuliczkowski K, Zdziarska B, Dmoszynska A, Marianska B, Pluta A, Zawilska K, Komarnicki M, Kloczko J, Sulek K, Haus O, Stella-Holowiecka B, Baran W, Jakubas B, Paluszewska M, Wierzbowska A, Kielbinski M, Jagoda K; Polish Adult Leukemia Group (PALG). Addition of cladribine to daunorubicin and cytarabine increases complete remission rate after a single course of induction treatment in acute myeloid leukemia. Multicenter, phase III study. Leukemia. 2004 May;18(5):989-97. doi: 10.1038/sj.leu.2403336.
- Background: PubMed 22508825Holowiecki J, Grosicki S, Giebel S, Robak T, Kyrcz-Krzemien S, Kuliczkowski K, Skotnicki AB, Hellmann A, Sulek K, Dmoszynska A, Kloczko J, Jedrzejczak WW, Zdziarska B, Warzocha K, Zawilska K, Komarnicki M, Kielbinski M, Piatkowska-Jakubas B, Wierzbowska A, Wach M, Haus O. Cladribine, but not fludarabine, added to daunorubicin and cytarabine during induction prolongs survival of patients with acute myeloid leukemia: a multicenter, randomized phase III study. J Clin Oncol. 2012 Jul 10;30(20):2441-8. doi: 10.1200/JCO.2011.37.1286. Epub 2012 Apr 16.
- 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.
Chun Wang, M.D.,Ph. D. study chair
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cladribine, Fludarabine and Busulfan in people with High Risk Acute Myeloid Leukemia and Allogeneic Hematopoeitic Stem Cell Transplantation, run by Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine at 1 site in China.
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 9 inclusion and 6 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 12 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Contact Jieling Jiang, M.D. (86-21-37798987, jiangjieling66@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
cumulative relapse rate at 2 year (time frame: 2 years). 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 NCT03384225, which also lists 2 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 12 Oct 2021.