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Evaluate the Hematological Remission Rates and Survival Among Chinese Adult Patients With B-precursor ALL

Completed
Conditions
B-precursor Acute Lymphoblastic Leukemia
Interventions
Other: salvage therapy
Registration Number
NCT03123887
Lead Sponsor
Harbin Hematology and Oncology Institute
Brief Summary

Although the response rate by first-line treatment has been improved, most adult patients with relapsed or refractory ALL will eventually relapse with poor outcomes regardless of treatments. To further understand current status of the treatment of adult patients with relapsed or refractory ALL in China, the study retrospectively collected diagnosis and treatment data from ALL patients in 14 centers in China. Primary objective: to estimate the proportion of patients in overall response rate (ORR) for early relapsed or primary refractory Philadelphia chromosome negative (Ph-) B-precursor ALL patients following salvage treatment (i.e., proportion of patients in hematological complete remission \[CR\] and CR with partial recovery of blood cells \[CRh\*\]); Secondary objectives included: to estimate the proportion of patients in CR, CRh\* and CRi(CR/CRh\*/CRi) and the duration of CR/CRh\*/CRi, overall survival, duration of CR/CRh\*and the proportion of patients receiving allogeneic hematopoietic stem cell transplantation (AlloHSCT) for early relapsed/primary refractory Ph-B-precursor ALL patients following salvage treatment; Exploratory objectives included: to estimate the efficacy in late relapsed Ph- B-precursor ALL (first remission duration \> 12 months) patients and in Ph+ B-precursor ALL patients and specific subgroup patients following salvage treatment.

Detailed Description

Title A Retrospective Study to Evaluate the Hematological Remission Rates and Survival Among Chinese Adult Patients with Relapsed or Refractory B-precursor Acute Lymphoblastic Leukemia (BLING)

Key Words Relapsed or refractory acute lymphoblastic leukemia, complete remission, duration of remission, overall survival, hematopoietic stem cell transplantation

Study Background and Rationale Although the response rate by first-line treatment has been improved, most adult patients with relapsed or refractory ALL will eventually relapse with poor outcome regardless of treatments. In order to improve the diagnosis and treatment level of adult ALL in China, Chinese Society of Hematology and Committee of Hematologic Malignancies of the Chinese Anti-Cancer Association released Expert Consensus on Diagnosis and Treatment of Acute Lymphoblastic Leukemia in Chinese Adult Patients in 2012. However, there is no nationwide multi-center retrospective observational study to evaluate the treatment status of adult patients with R/r ALL (including treatment regimens, and remission rate, overall survival and rate of allogeneic hematopoietic stem cell transplantation of R/r ALL patients following standard salvage chemotherapy), and these data will provide an important reference for further standardization of the treatment of ALL in China, improvement of the prognosis and the research and development of new drugs.

Study questions and Objectives

Primary objectives:

To estimate the proportion of patients in overall response rate (ORR) for early relapsed (a first remission duration of ≤12 months) or primary refractory R/r Philadelphia chromosome negative (Ph-) B-precursor ALL patients following salvage treatment (i.e., proportion of patients in hematological complete remission \[CR\] and CR with partial recovery of blood cells \[CRh\*\]).

Secondary objectives:

To estimate the proportion of patients in CR, CRh\* or CRi for early relapsed/primary refractory Ph-B-precursor ALL patients following salvage treatment (CR/CRh\*/CRi) To estimate overall survival (OS) for early relapsed/primary refractory Ph-B-precursor ALL patients following salvage treatment To estimate the duration of CR/CRh\* for early relapsed/primary refractory Ph-B-precursor ALL patients following salvage treatment To estimate the duration of CR/CRh\*/CRi for early relapsed/primary refractory Ph- B-precursor ALL patients following salvage treatment To estimate the proportion of patients receiving allogeneic hematopoietic stem cell transplantation (AlloHSCT) among early relapsed/primary refractory Ph- B-precursor ALL patients following salvage treatment To examine the potential prognostic factors of early relapsed/primary refractory Ph-B-precursor ALL patients by performing subgroup and regression analyses To estimate overall response rate (CR/CRh\*), CR/CRh\*/CRi, overall survival (OS), duration of CR/CRh\*/CRi, duration of CR/CRh\* and the proportion of patients receiving allogeneic hematopoietic stem cell transplantation (AlloHSCT) after CR or CRh\* among Ph- B-precursor ALL patients with duration of first CR ≤ 12 months following first salvage treatment

Exploratory objectives:

To estimate the proportion of patients in CR/CRh\*, duration of CR/CRh\*, proportion of patients in CR/CRh\*/CRi, duration of CR/CRh\*/CRi, OS and proportion of patients receiving AlloHSCT following salvage treatment for late relapsed (a first remission duration of \>12 months) Ph- B-precursor ALL To estimate the proportion of patients in CR/CRh\*, duration of CR/CRh\*, proportion of patients in CR/CRh\*/CRi, duration of CR/CRh\*/CRi, OS and the proportion of patients receiving AlloHSCT for Ph+ B-precursor ALL patients and specific subgroup of patients following treatment for R/r B-precursor ALL To examine the potential prognostic factors of late relapsed Ph- B-precursor ALL patients and Ph+ B-precursor ALL patients To describe the types of chemotherapy regimens received and the corresponding efficacy results of main regimens, among patients following primary and salvage treatment for R/r B-precursor ALL Study Design This study was a retrospective study in which data were retrospectively collected from patients with R/r B-precursor ALL in 14 main hematologic malignancy centers in China. Patient subgroups were defined by factors that might influence ORR and OS to better understand their effects on study endpoints.

Subjects and Study Size

The study selected patients with R/r B-precursor ALL meeting inclusion criteria. Specific inclusion criteria were as follows:

Chinese adult patients with R/r B-precursor ALL who had received salvage treatment At least one complete response evaluation results available for salvage treatment With definite Ph chromosome status Age ≥15 years at time of de novo (initial) diagnosis of ALL. For relapsed patients who met the above conditions must also have

1. Evaluable duration of CR by initial therapy, 2. No central nervous system involved at relapsed, 3. No isolated extramedullary relapse.

Patients were divided into 3 analysis sets based on molecular genetic factor and type, and time from initial response to relapse. Ph- Primary Analysis Set included patients who are diagnosed with Ph- disease and meet one of the following criteria: in first relapse or salvage treatment after a first complete remission duration of ≤12 months, or refractory to initial treatment, or relapsed/refractory after first or subsequent salvage treatment, or Relapsed/refractory within 12 months after allogeneic hematopoietic stem cell transplantation (AlloHSCT). The Ph- Late Relapse Analysis Set included patients who had a first remission duration of \>12 months and were in first relapse or salvage treatment. The Ph+ Analysis Set included patients who were diagnosed with Ph+ disease.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
632
Inclusion Criteria
  • Chinese adult patients with R/r B-precursor ALL who had received salvage treatment
  • At least one complete response evaluation results available for salvage treatment
  • With definite Ph chromosome status
  • Age ≥15 years at time of de novo (initial) diagnosis of ALL.
  • For relapsed patients who met the above conditions must also have
  • Evaluable duration of CR by initial therapy
  • No central nervous system involved at relapsed
  • No isolated extramedullary relapse Patients were divided into 3 analysis sets based on molecular genetic factor and type, and time from initial response to relapse.
  • Ph- Primary Analysis Set included patients who are diagnosed with Ph- disease and meet one of the following criteria:
  • in first relapse or salvage treatment after a first complete remission duration of ≤12 months, or refractory to initial treatment, or relapsed/refractory after first or subsequent salvage treatment, or Relapsed/refractory within 12 months after alloHSCT.
  • The Ph- Late Relapse Analysis Set included patients who had a first remission duration of >12 months and were in first relapse or salvage treatment.
  • The Ph+ Analysis Set included patients who were diagnosed with Ph+ disease.
Exclusion Criteria

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
R/r B-precursor ALLsalvage therapyThis study selected patients with Relapsed or Refractory (R/r) B-precursor Acute Lymphoblastic Leukemia
Primary Outcome Measures
NameTimeMethod
overall response rateup to 3 years

overall response rate after the last salvage therapy, i.e., CR/CRh\*. CR is generally defined as no blasts in peripheral blood, absence of extramedullary leukemia, full recovery of peripheral blood counts, ≤ 5% blasts in the bone marrow, ANC \> 1.0×109/L, PLT \> 100×109/L, no relapse within 4 weeks. CRh\* was CR with partial recovery of peripheral blood counts, ANC \> 0.5×109/L, PLT \> 50×109/L, with other conditions meeting the criteria for CR

Secondary Outcome Measures
NameTimeMethod
proportion of patients in CR, CRh* or CRiup to 3 years

the proportion of patients in CR, CRh\* or CRi for early relapsed/primary refractory Ph- B-precursor ALL patients following last salvage treatment

overall survivalup to 3 years

overall survival (OS) among R/r Ph- B-precursor ALL patients after achieving CR or CRh\* after the first salvage therapy

duration of remission (CR/CRh*, CR/CRh*/CRi)up to 3 years

duration of remission (CR/CRh\*, CR/CRh\*/CRi) for early relapsed/primary refractory Ph- B-precursor ALL patients after CR or CRh\* achieved

proportion of patients receiving allogeneic hematopoietic stem cell transplantationup to 3 years

the proportion of patients receiving allogeneic hematopoietic stem cell transplantation (AlloHSCT) among early relapsed/primary refractory Ph- B-precursor ALL patients following salvage treatment

duration of CR/CRh*/CRiup to 3 years

duration of CR/CRh\* among R/r Ph- B-precursor ALL patients after achieving CR or CRh\* after the first salvage therapy

the proportion of patients receiving allogeneic hematopoietic stem cell transplantation (AlloHSCT)up to 3 years

the proportion of patients receiving allogeneic hematopoietic stem cell transplantation (AlloHSCT) after CR or CRh\* achieved among R/r Ph- B-precursor ALL patients after achieving CR or CRh\* after the first salvage therapy

Complete Responseup to 3 years

Complete Response among R/r Ph- B-precursor ALL patients after achieving CR or CRh\* after the first salvage therapy

Complete Response with incomplete recovery of blood cellsup to 3 years

Complete Response with incomplete recovery of blood cells among R/r Ph- B-precursor ALL patients after achieving CR or CRh\* after the first salvage therapy

Complete Response with partial recovery of blood cellsup to 3 years

Complete Response with partial recovery of blood cells among R/r Ph- B-precursor ALL patients after achieving CR or CRh\* after the first salvage therapy

duration of CR/CRh*up to 3 years

duration of CR/CRh\* with partial recovery of blood cells among R/r Ph- B-precursor ALL patients after achieving CR or CRh\* after the first salvage therapy

Trial Locations

Locations (1)

Institute of Harbin Hematology Oncology

🇨🇳

Harbin, Heilongjiang, China

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