Philadelphia Chromosome Positive Acute Lymphocytic LeukemiaPhase 2NCT01883219
TKI Therapy Based on Molecular Monitoring in Allogeneic-HSCT Recipients With Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia
A Phase 2 study testing TKIs in people with Philadelphia Chromosome Positive Acute Lymphocytic Leukemia and Stem Cell Transplantation, run by Nanfang Hospital, Southern Medical University at 1 site in China.
Trial summary
The purpose of this study is to evaluate the efficacy of tyrosine kinase inhibitor(TKI) therapy based on molecular monitoring of BCR/ABL levels in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL)undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT). Read more about this study
- Who is it for?
- Ages 14 to 65 years
- Conditions the study is for
- Philadelphia Chromosome Positive Acute Lymphocytic Leukemia, Stem Cell Transplantation, Minimal Residual Disease
- What is being tested?
- TKIs
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteChina
- Study dates
- Jun 2013to Nov 2017
- Phase
- Phase 2
- 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 14 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- A patient age of 14-65 years
- Allo-HSCT recipient with ph+ ALL
- Subjects (or their legally acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.
Who cannot join
- Any abnormality in a vital sign (e.g., heart rate, respiratory rate, or blood pressure)
- patients with hematological relapse, extramedullary involvement of leukemia
- Patients with any conditions not suitable for the trial (investigators' decision)
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Department of Hematology,Nanfang Hospital, Southern Medical University
Guangzhou, Guangdong, 510515
Ren Lin, MD, +86-020-61641613, lansinglinren@hotmail.com
About this study
Official title: Tyrosine Kinase Inhibitor Therapy Based on Molecular Monitoring of BCR/ABL Transcript Levels in Allogeneic Hematopoietic Stem Cell Transplant Recipients With Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia
The purpose of this study is to evaluate the efficacy of tyrosine kinase inhibitor(TKI) therapy based on molecular monitoring of BCR/ABL levels in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL)undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT).
Read the detailed description
Philadelphia chromosome (Ph) is a reciprocal chromosomal translocation t(9;22）(q34;q11), which leads to the formation of the BCR/ABL oncogene. Ph is the most frequent cytogenetic abnormality in ALL characterized by poor outcome. With the BCR/ABL protein TKI, imatinib, in the combination chemotherapy regimes for newly diagnosed Ph+ ALL, more than 95% of patients can achieve complete remission(CR). Several studies have shown decreased relapse rates and improved disease-free survival for patients with imatinib-based treatment prior to allo-HSCT. However, the efficacy of maintenance therapy with imatinib after transplant for Ph+ ALL patients is still uncertain. In addition, acquired resistance to imatinib is frequently caused by point mutations in BCR/ABL that inactivate imatinib.
Detection of minimal residual disease (MRD) after transplant is associated with an increased risk of relapse. Reverse transcription-polymerase chain reaction (RT-PCR) is a sensitive method for detecting low-level BCR/ABL transcripts to assess MRD in Ph+ ALL. It has been corroborated by several reports that detection of MRD after SCT was predictive of imminent relapse.
In this study, we will evaluate the safety and efficacy of TKI therapy, when initiating treatment based on BCR-ABL transcript levels after allo-HSCT.
- Conditions
- Philadelphia Chromosome Positive Acute Lymphocytic Leukemia, Stem Cell Transplantation, Minimal Residual Disease
- Being tested
- TKIs
- Keywords
- Philadelphia chromosome, Acute lymphoblastic leukemia, Allogeneic hematopoietic cell transplantation, Minimal residual disease, Tyrosine kinase inhibitor
- Medical subject headings
- Neoplasm, Residual, Philadelphia Chromosome, Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TKIsDrug
Imatinib was given at a dose of 400mg/d or 600mg/d, dasatinib at a dose of 100mg/d or 140mg/d, and nilotinib at a dose of 400mg twice daily. If the patients had T315I mutations, ponatinib will be given. If the BCR/ABL levels increased or did not decrease after one month's use of TKI, donor lymphocyte infusion will be given and the TKI drugs will be modulated. If the patients experienced hematologic relapse, they will withdraw from the study.
| Study group | Role | What they receive |
|---|---|---|
| TKI therapy | Experimental | Treatment with TKI will be initiated if the level of BCR-ABL transcript in the bone marrow is detectable and transcript levels increased for two consecutive tests. TKIs will be given for patients without BCR/ABL mutations and sensitive TKIs will be given for those with mutations. Receives: Drug: TKIs |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival(OS)
OS is defined as continuous survival until death from any cause after HSCT.
Measured: 2 years
Secondary outcomes (3)
Relapse rate
A post-transplant relapse is defined as hematological relapse, extramedullary involvement of leukemia and cytogenetic relapse.
Measured: 2 years
Disease-free survival(DFS)
DFS is defined as continuous survival without relapse or death from any cause after HSCT.
Measured: 2 years
Safety of TKI therapy
The toxicity of TKI is assessed according to the Common Toxicity Criteria, version 3.0.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2013 (estimated)
- Study startJun 2013
- Primary completionJun 2016
- Study completionNov 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Philadelphia Chromosome Positive Acute Lymphocytic LeukemiaStudies of the same condition, open and under way.
- More trials run by Nanfang Hospital, Southern Medical UniversityThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nanfang Hospital, Southern Medical University
- Sponsor type
- University, hospital or other
- Collaborators
- Peking University People's Hospital, Guangxi Medical University, Guangdong Provincial People's Hospital, Guangzhou General Hospital of Guangzhou Military Command, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Third Affiliated Hospital, Sun Yat-Sen University
- Responsible party
- Principal investigator, Qifa Liu, Nanfang Hospital, Southern Medical University
- Investigators
- Qifa Liu, MD, Principal investigator, Nanfang Hospital, Southern Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01883219
- Sponsor's protocol ID
- NFEC-201304-K2
- Status last verified
- Jun 2013
- First submitted
- 14 Jun 2013
- Last updated
- 8 Nov 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Yanada M, Sugiura I, Takeuchi J, Akiyama H, Maruta A, Ueda Y, Usui N, Yagasaki F, Yujiri T, Takeuchi M, Nishii K, Kimura Y, Miyawaki S, Narimatsu H, Miyazaki Y, Ohtake S, Jinnai I, Matsuo K, Naoe T, Ohno R; Japan Adult Leukemia Study Group. Prospective monitoring of BCR-ABL1 transcript levels in patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia undergoing imatinib-combined chemotherapy. Br J Haematol. 2008 Nov;143(4):503-10. doi: 10.1111/j.1365-2141.2008.07377.x.
PubMed 18986386Wassmann B, Pfeifer H, Stadler M, Bornhauser M, Bug G, Scheuring UJ, Bruck P, Stelljes M, Schwerdtfeger R, Basara N, Perz J, Bunjes D, Ledderose G, Mahlberg R, Binckebanck A, Gschaidmeier H, Hoelzer D, Ottmann OG. Early molecular response to posttransplantation imatinib determines outcome in MRD+ Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Blood. 2005 Jul 15;106(2):458-63. doi: 10.1182/blood-2004-05-1746. Epub 2005 Apr 7.
PubMed 15817679Liu H, Xuan L, Lin R, Deng L, Fan Z, Nie D, Li X, Liang X, Xu D, Zhang Y, Xu N, Ye J, Jin H, Lin D, Ma L, Sun J, Huang F, Liu Q. A new pre-emptive TKIs strategy for preventing relapse based on BCR/ABL monitoring for Ph+ALL undergoing allo-HCT: a prospective clinical cohort study. Leukemia. 2021 Jul;35(7):2054-2063. doi: 10.1038/s41375-020-01090-4. Epub 2020 Nov 17.
PubMed 33204013
Study at a glance
From the registry record, last updated by the sponsor on 8 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tyrosine Kinase Inhibitor Therapy Based on Molecular Monitoring of BCR/ABL Transcript Levels in Allogeneic Hematopoietic Stem Cell Transplant Recipients With Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia
- ClinicalTrials.gov ID
- NCT01883219
- Acronym / sponsor ID
- NFEC-201304-K2
- Conditions
- Philadelphia Chromosome Positive Acute Lymphocytic Leukemia, Stem Cell Transplantation, Minimal Residual Disease
- Keywords
- Philadelphia chromosome, Acute lymphoblastic leukemia, Allogeneic hematopoietic cell transplantation, Minimal residual disease, Tyrosine kinase inhibitor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Nanfang Hospital, Southern Medical UniversityUniversity, hospital or other
- Collaborators
- Peking University People's Hospital, Guangxi Medical University, Guangdong Provincial People's Hospital, Guangzhou General Hospital of Guangzhou Military Command, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Third Affiliated Hospital, Sun Yat-Sen University
- Study start
- Jun 2013
- Primary completion
- Jun 2016 (actual)
- Study completion
- Nov 2017 (estimated)
- First posted
- 21 Jun 2013 (estimated)
- 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.
The purpose of this study is to evaluate the efficacy of tyrosine kinase inhibitor(TKI) therapy based on molecular monitoring of BCR/ABL levels in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL)undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT).
Detailed description
Philadelphia chromosome (Ph) is a reciprocal chromosomal translocation t(9;22）(q34;q11), which leads to the formation of the BCR/ABL oncogene. Ph is the most frequent cytogenetic abnormality in ALL characterized by poor outcome. With the BCR/ABL protein TKI, imatinib, in the combination chemotherapy regimes for newly diagnosed Ph+ ALL, more than 95% of patients can achieve complete remission(CR). Several studies have shown decreased relapse rates and improved disease-free survival for patients with imatinib-based treatment prior to allo-HSCT. However, the efficacy of maintenance therapy with imatinib after transplant for Ph+ ALL patients is still uncertain. In addition, acquired resistance to imatinib is frequently caused by point mutations in BCR/ABL that inactivate imatinib.
Detection of minimal residual disease (MRD) after transplant is associated with an increased risk of relapse. Reverse transcription-polymerase chain reaction (RT-PCR) is a sensitive method for detecting low-level BCR/ABL transcripts to assess MRD in Ph+ ALL. It has been corroborated by several reports that detection of MRD after SCT was predictive of imminent relapse.
In this study, we will evaluate the safety and efficacy of TKI therapy, when initiating treatment based on BCR-ABL transcript levels after allo-HSCT.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TKI therapy | Experimental | Drug: TKIsTreatment with TKI will be initiated if the level of BCR-ABL transcript in the bone marrow is detectable and transcript levels increased for two consecutive tests. TKIs will be given for patients without BCR/ABL mutations and sensitive TKIs will be given for those with mutations. |
Who may qualify
- Ages
- 14 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- A patient age of 14-65 years
- Allo-HSCT recipient with ph+ ALL
- Subjects (or their legally acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.
Key exclusion criteria (3 listed)
- Any abnormality in a vital sign (e.g., heart rate, respiratory rate, or blood pressure)
- patients with hematological relapse, extramedullary involvement of leukemia
- Patients with any conditions not suitable for the trial (investigators' decision)
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 |
|---|---|---|
| TKIsImatinib was given at a dose of 400mg/d or 600mg/d, dasatinib at a dose of 100mg/d or 140mg/d, and nilotinib at a dose of 400mg twice daily. If the patients had T315I mutations, ponatinib will be given. If the BCR/ABL levels increased or did not decrease after one month's use of TKI, donor lymphocyte infusion will be given and the TKI drugs will be modulated. If the patients experienced hematologic relapse, they will withdraw from the study. | Drug | TKI therapy |
Primary outcome
Overall survival(OS)
Time frame: 2 years
OS is defined as continuous survival until death from any cause after HSCT.
3 secondary outcomes
Relapse rate
Time frame: 2 years
Disease-free survival(DFS)
Time frame: 2 years
Safety of TKI therapy
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Nov 2017.
- Background: PubMed 18986386Yanada M, Sugiura I, Takeuchi J, Akiyama H, Maruta A, Ueda Y, Usui N, Yagasaki F, Yujiri T, Takeuchi M, Nishii K, Kimura Y, Miyawaki S, Narimatsu H, Miyazaki Y, Ohtake S, Jinnai I, Matsuo K, Naoe T, Ohno R; Japan Adult Leukemia Study Group. Prospective monitoring of BCR-ABL1 transcript levels in patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia undergoing imatinib-combined chemotherapy. Br J Haematol. 2008 Nov;143(4):503-10. doi: 10.1111/j.1365-2141.2008.07377.x.
- Background: PubMed 15817679Wassmann B, Pfeifer H, Stadler M, Bornhauser M, Bug G, Scheuring UJ, Bruck P, Stelljes M, Schwerdtfeger R, Basara N, Perz J, Bunjes D, Ledderose G, Mahlberg R, Binckebanck A, Gschaidmeier H, Hoelzer D, Ottmann OG. Early molecular response to posttransplantation imatinib determines outcome in MRD+ Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Blood. 2005 Jul 15;106(2):458-63. doi: 10.1182/blood-2004-05-1746. Epub 2005 Apr 7.
- Derived from this study: PubMed 33204013Liu H, Xuan L, Lin R, Deng L, Fan Z, Nie D, Li X, Liang X, Xu D, Zhang Y, Xu N, Ye J, Jin H, Lin D, Ma L, Sun J, Huang F, Liu Q. A new pre-emptive TKIs strategy for preventing relapse based on BCR/ABL monitoring for Ph+ALL undergoing allo-HCT: a prospective clinical cohort study. Leukemia. 2021 Jul;35(7):2054-2063. doi: 10.1038/s41375-020-01090-4. Epub 2020 Nov 17.
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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.
Qifa Liu, MD principal investigator
Nanfang Hospital, Southern Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TKIs in people with Philadelphia Chromosome Positive Acute Lymphocytic Leukemia and Stem Cell Transplantation, run by Nanfang Hospital, Southern Medical University 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 3 inclusion and 3 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 8 Nov 2017. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Ren Lin, MD (+86-020-61641613, lansinglinren@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall survival(OS) (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 NCT01883219, which also lists 3 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 8 Nov 2017.