Newly-diagnosed Pediatric Ph-positive B-ALL Protocol
CAMS-Ph+ B-ALL
A Phase 3, Multicenter Trial for Pediatric Philadelphia Chromosome-positive B-Acute Lymphoblastic Leukemia -2025 Project
1 other identifier
interventional
150
2 countries
24
Brief Summary
This prospective clinical trial evaluates the effectiveness and safety of "chemotherapy-light" regimen incorporating the third-generation TKI olverembatinib, the bi-specific CD3/CD19 T cell engager blinatumomab, and the BCL-2 selective inhibitor venetoclax for newly diagnosed pediatric/adolescent patients with Ph+ ALL. The CCCG-Ph+ B-ALL-2025 protocol will be modified as following compared to the CCCG-ALL-2020 protocol
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Mar 2025
Longer than P75 for phase_3
24 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 28, 2025
CompletedStudy Start
First participant enrolled
March 28, 2025
CompletedFirst Posted
Study publicly available on registry
September 3, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 1, 2030
September 3, 2025
August 1, 2025
4.7 years
March 28, 2025
August 28, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Day 48 end-of-induction measurable residual diseases (MRD48) after induction remission with olverembatinib and blinatumomab, compared to MRD46 of those treated with dasatinib plus chemotherapy induction (CCCG-ALL-2015 /2020) or from historical cohorts .
Primary analysis will be performed by one-sided (Monte-Carlo-) exact chi-square test because the objective calls for testing if the proportion of patients in the \<0.01% Day 48 MRD group is higher than the historical control. The historical control of Day 46 MRD of dasatinib combination with intensive chemotherapy is 80%. It is estimated that VPO+Blinatumomab can increase the negative rate of Day 48 MRD by 10%. a total sample size of 135 provides sufficient power for the planned analyses outlined above if the true D48 MRD negativity probability is 0.90 or higher based on a one-sided alpha of 0.05.
Up to approximately 4.5 years.
Secondary Outcomes (4)
Day 19 measurable residual diseases (MRD19) during induction remission with olverembatinib plus VP (VOP), compared to MRD19 of those treated with dasatinib plus 4-drug chemotherapy induction (CCCG-ALL-2015 /2020) or from historical cohorts
Approximately 4.5 years.
Event-free survival (EFS) of patients treated with this therapy, in comparison to historical regimens.
Approximately 7 years.
Overall survival (OS) of patients treated with this therapy, in comparison to historical regimens
Approximately 7 years.
Cumulative incidence of relapse (CIR) of this therapy, in comparison to historical regimens.
Approximately 7 years.
Other Outcomes (10)
To correlate measurable residual diseases (MRD) during remission induction and after consolidation by Ig-NGS, qPCR of BCR::ABL1 and FCM-MRD with cumulative incidence of event-free survival (EFS)
Approximately 7 years
To correlate measurable residual diseases (MRD) during remission induction and after consolidation by Ig-NGS, qPCR of BCR::ABL1 and FCM-MRD with cumulative incidence of relapse(CIR)
Approximately 7 years
To correlate measurable residual diseases (MRD) during remission induction and after consolidation by Ig-NGS, qPCR of BCR::ABL1 and FCM-MRD with overall survival (OS)
Approximately 7 years
- +7 more other outcomes
Study Arms (1)
OVB+Blina+VEN+Chemo-light regimen
EXPERIMENTALAll Ph+-ALL patients will uniformly use the 3rd generation of TKI olverembatinib (OVB) instead of dasatinib throughout the regimen. Cyclophosphamide and asparaginase are totally omitted from the entire treatment to mitigate toxicities. OVB is combined with Vincristine and Prednisone (VP) during the first 2 weeks and with blinatumomab during the last 4 weeks of remission induction in this protocol. Patients will receive blinatumomab for 28 days as induction instead of CAT to improve induction response and avoid toxicity. All patients will receive two cycles of HDMTX+Blina-14 and 4 times of triple intrathecal therapy (TIT) throughout the consolidation 1 phase. The dosage of AraC will be reduced to 1 g/m2 in the consolidation 2 phase. Throughout the early Maintenance Therapy, dexamethasone and vincristine combination will be added with either venetoclax or daunorubicin alternatively for five cycles, given after MTX and 6-MP.
Interventions
All Ph+-ALL patients will uniformly use the 3rd generation of TKI olverembatinib (OVB) instead of dasatinib throughout the regimen. OVB is combined with Vincristine and Prednisone (VP) during the first 2 weeks and with blinatumomab during the last 4 weeks of remission induction in this protocol. Patients will receive blinatumomab for 28 days as induction instead of CAT to improve induction response and avoid toxicity. All patients will receive two cycles of HDMTX+Blina-14 and 4 times of triple intrathecal therapy (TIT) throughout the consolidation 1 phase. To decrease the toxicities of high-dose AraC, the dosage will be reduced to 1 g/m2 in the consolidation 2 phase in contrast to 2 g/m2 in 2020 protocol. Throughout the early Maintenance Therapy, dexamethasone and vincristine combination will be added with either venetoclax or daunorubicin alternatively for five cycles, given after MTX and 6-MP.
Eligibility Criteria
You may qualify if:
- Must meet all items below:
- Age older than 1 month to younger 18 years.
- Newly diagnosed Philadelphia chromosome-positive or BCR::ABL1-positive B-ALL.
- Written informed consent of the parents or other legally authorized guardian of the patient according to local law and regulations.
You may not qualify if:
- Should be excluded if had any item below:
- ALL evolved from CML.
- Known underlying congenital immunodeficiency or metabolic disease.
- Congenital heart disease with cardiac insufficiency.
- Gastrointestinal dysfunction or gastrointestinal diseases that may significantly alter the absorption of study drug.
- Severe malnutrition, uncontrolled active infections, or serious cardiovascular diseases.
- Subjects with significant CNS disorder (e.g., uncontrolled seizure disorder, autoimmune disease involving CNS).
- Treated with glucocorticoids for ≥14 days, or targeted inhibitor for \> 7 days within one month before enrollment, or any chemotherapy or any systemic anticancer therapy (including but not limited to any TKI) or radiotherapy within 3 months before enrollment (except for emergency radiotherapy to relieve airway compression).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (24)
Anhui Medical University Second Affiliated Hospita
Hefei, Anhui, China
Chongqing Medical University Affiliated Children's Hospital
Chongqing, Chongqing Municipality, China
Fujian Medical University Union Hospital
Fuzhou, Fujian, China
Guangzhou Women and Children's Medical Center
Guangzhou, Guangdong, China
Nanfang Hospital, Southern Medical University
Guangzhou, Guangdong, China
The First Affiliated Hospital, Sun Yat-sen University
Guangzhou, Guangdong, China
The Affiliated Hospital of Guizhou Medical University
Guiyang, Guizhou, China
Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, China
Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, China
Wuhan Children's Hospital
Wuhan, Hubei, China
Hunan Children's Hospital
Changsha, Hunan, China
The Third Xiangya Hospital of the Central South University
Changsha, Hunan, China
Nanjing Children's Hospital Affiliated to Nanjing Medical University
Nanjin, Jiangsu, China
Children's Hospital of Soochow University
Suzhou, Jiangsu, China
Jiangxi Provincial Children's Hospital
Nanchang, Jiangxi, China
Qilu Hospital of Shandong University
Jinan, Shandong, China
Affiliated Hospital of Qingdao University
Qingdao, Shandong, China
Children's Hospital of Fudan University
Shanghai, Shanghai Municipality, China
Shanghai Children's Hospital
Shanghai, Shanghai Municipality, China
Shenzhen Children's Hospital
Shenzhen, Shenzhen, China
West China Second University Hospita
Chengdu, Sichuan, China
Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC
Tianjin, Tianjin Municipality, China
Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC
Tianjin, Tianjin Municipality, China
Hong Kong Children's Hospital, The Chinese University of Hong Kong
Hong Kong, Hong Kong
Related Publications (6)
Manabe A, Kawasaki H, Shimada H, Kato I, Kodama Y, Sato A, Matsumoto K, Kato K, Yabe H, Kudo K, Kato M, Saito T, Saito AM, Tsurusawa M, Horibe K. Imatinib use immediately before stem cell transplantation in children with Philadelphia chromosome-positive acute lymphoblastic leukemia: Results from Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) Study Ph(+) ALL04. Cancer Med. 2015 May;4(5):682-9. doi: 10.1002/cam4.383. Epub 2015 Jan 31.
PMID: 25641907BACKGROUNDHum RM, Deambrosis D, Lum SH, Davies E, Bonney D, Guiver M, Turner A, Wynn RF, Hiwarkar P. Molecular monitoring of adenovirus reactivation in faeces after haematopoietic stem-cell transplantation to predict systemic infection: a retrospective cohort study. Lancet Haematol. 2018 Sep;5(9):e422-e429. doi: 10.1016/S2352-3026(18)30130-3.
PMID: 30172346BACKGROUNDBiondi A, Schrappe M, De Lorenzo P, Castor A, Lucchini G, Gandemer V, Pieters R, Stary J, Escherich G, Campbell M, Li CK, Vora A, Arico M, Rottgers S, Saha V, Valsecchi MG. Imatinib after induction for treatment of children and adolescents with Philadelphia-chromosome-positive acute lymphoblastic leukaemia (EsPhALL): a randomised, open-label, intergroup study. Lancet Oncol. 2012 Sep;13(9):936-45. doi: 10.1016/S1470-2045(12)70377-7. Epub 2012 Aug 14.
PMID: 22898679BACKGROUNDSchultz KR, Carroll A, Heerema NA, Bowman WP, Aledo A, Slayton WB, Sather H, Devidas M, Zheng HW, Davies SM, Gaynon PS, Trigg M, Rutledge R, Jorstad D, Winick N, Borowitz MJ, Hunger SP, Carroll WL, Camitta B; Children's Oncology Group. Long-term follow-up of imatinib in pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia: Children's Oncology Group study AALL0031. Leukemia. 2014 Jul;28(7):1467-71. doi: 10.1038/leu.2014.30. Epub 2014 Jan 20.
PMID: 24441288BACKGROUNDSchultz KR, Bowman WP, Aledo A, Slayton WB, Sather H, Devidas M, Wang C, Davies SM, Gaynon PS, Trigg M, Rutledge R, Burden L, Jorstad D, Carroll A, Heerema NA, Winick N, Borowitz MJ, Hunger SP, Carroll WL, Camitta B. Improved early event-free survival with imatinib in Philadelphia chromosome-positive acute lymphoblastic leukemia: a children's oncology group study. J Clin Oncol. 2009 Nov 1;27(31):5175-81. doi: 10.1200/JCO.2008.21.2514. Epub 2009 Oct 5.
PMID: 19805687BACKGROUNDArico M, Schrappe M, Hunger SP, Carroll WL, Conter V, Galimberti S, Manabe A, Saha V, Baruchel A, Vettenranta K, Horibe K, Benoit Y, Pieters R, Escherich G, Silverman LB, Pui CH, Valsecchi MG. Clinical outcome of children with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia treated between 1995 and 2005. J Clin Oncol. 2010 Nov 1;28(31):4755-61. doi: 10.1200/JCO.2010.30.1325. Epub 2010 Sep 27.
PMID: 20876426BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Xiaofan Zhu, MD
Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 28, 2025
First Posted
September 3, 2025
Study Start
March 28, 2025
Primary Completion (Estimated)
December 1, 2029
Study Completion (Estimated)
June 1, 2030
Last Updated
September 3, 2025
Record last verified: 2025-08
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
- Time Frame
- IPD will be made available upon publication of the primary trial results or after trial completion, whichever occurs first, starting on 2032, and will remain accessible for 5 years.
- Access Criteria
- Researchers, healthcare professionals who meet the criteria for access (e.g., academic researchers conducting secondary analyses or regulatory bodies reviewing safety data) will be able to request access to de-identified IPD and supporting information. Access will be facilitated through clinical trials.gov/emailing to PI, where users can submit a request and provide a research proposal. Data access will be granted after a formal review and approval process, subject to compliance with the data-sharing agreement and confidentiality terms.
1. Demographic Data: Age, sex, and other relevant baseline characteristics. 2. Treatment Information: Data on interventions received by participants, including dosage, treatment cycles, and duration. 3. Outcome Measures: Detailed information on primary and secondary outcome measures, such as response rates, survival rates, adverse events, and any the pre-specified endpoints. 4. Adverse Events: Data on all reported adverse events, including severity, duration, and outcome. 5. Laboratory Data: Results from laboratory tests, such as blood counts, biochemical markers, or molecular analysis. 6. Medical History: Pre-existing conditions, comorbidities, and prior treatments or interventions. 7. Vital Signs: relevant physiological data. 8. Efficacy and Safety Data: Any data relating to the efficacy (e.g., event-free survival) and safety (e.g., adverse effects) of the treatment.