Comparative Study of BFC and BuCy Conditioning Regimen for Allo-PBSCT in Acute B-cell ALL

Shanghai General Hospital, Shanghai, Jiao Tong University School of Medicine

Comparing the efficacy and safety of fludarabine-containing BFC conditioning regimen with traditional BuCy conditioning regimen in Acute B-cell lymphoblastic leukemia patients who treated with allogeneic hematopoietic stem cell transplantation, to establish a conditioning regimen for improving the survival rate of patients with B-cell ALL after transplantation.

Acute B-cell lymphoblastic leukemia (B-ALL) is a hematologic malignancy . The incidence of B-All is higher in children than in adults, but more than 80% of children patients can be cured by chemotherapy, while the survival rate of adult patients is less than 40%. Recurrence or progression of the disease is the main reason affecting the survival of patients.

Although CD19-targeted CAR T cell therapy is an effective salvage treatment for relapsed and refractory B-ALL, bridging allogeneic hematopoietic stem cell transplantation is required after remission. 1-year LFS and 1-year OS were 11.6% and 32% in patients without bridging grafts after CAR T.

Allogeneic hematopoietic stem cell transplantation is an effective treatment for ALL. Before the transplant, patients receive high doses of chemotherapy plus or total body irradiation（TBI） to 'creation of space' ，immunosuppression and disease eradication. This is called conditioning regimen. Conditioning regimen plays a key role in reducing tumor load and diseaseconditioning regimen recurrence.

Conditioning regimen for different diseases are different. Conditioning regimen are based on TBI and chemotherapy BuCy, with low TBI recurrence rate but high treatment-related mortality (TRM). BuCY chemotherapy had low TRM but high recurrence rate, so there was no difference in total OS. Therefore, it is of great clinical value to explore a conditioning regimenprogram. How to optimize the preconditioning program before transplantation, so as to reduce the recurrence rate and prolong the survival period of adult B-cell ALL patients after transplantation has become a issue that needs to be solved urgently in clinical practice.

BFC (Malilane + fludarabine + cyclophosphamide) is the addition of fludarabine to BuCy (malilane + cyclophosphamide). The combination of fludarabine and cyclophosphamide has synergistic effect, which can better kill B lymphocyte, and can enhance the killing effect of pretreatment regimen on B lymphocyte tumor.

Study Overview

• Status: Recruiting
• Conditions: Allogeneic Hematopoietic Stem Cell Transplantation; Acute B Lymphoblastic Leukemia
• Intervention / Treatment: Drug: Fludarabine

Detailed Description

This study was a prospective, randomized, controlled, single-center clinical study. A total of 142 patients eligible for the inclusion of acute B lymphoblastic leukemia were randomly divided into two groups: the experimental group (n = 71) and the control group (n = 71). The treatment group was given BFC conditioning regimen (fludalabine, marylan, cyclophosphamide), and the control group was given BuCY conditioning regimen (marylan, cyclophosphamide), and the patients were followed up to 1 year after transplantation. The 1-year disease-free survival rate of patients in the two groups was compared to evaluate whether increasing fludarabine could reduce the recurrence rate of patients after transplantation and thus improve the overall survival rate.

• Study Type: Interventional
• Enrollment (Anticipated): 142
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Yu Cai, MD; Phone Number: +86-13818583066; Email: butterflymmyu@hotmail.com

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Shanghai General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Ages 18-55.
2. The patient was diagnosed as acute B-lymphoblastic leukemia, which was confirmed by bone marrow cell morphology, cytochemistry, immunotyping and chromosome examination, including acute chronic myelocytic leukemia, Ph-acute B-lymphoblastic leukemia, and acute B-lymphoblastic leukemia after CART treatment.
3. The diagnostic criteria for b-blastic leukemia in remission were: complete hematologic response (CR) with negative minimal residual lesions (MRD) after regular induction of remission chemotherapy, or complete hematologic response with negative MRD after CART treatment.
4. ECOG physical fitness status score ≤2.

5. All organs function normally and meet the following inspection standards:

   A) Liver function ALT, AST and TBIL≤2 times the upper limit of normal value B) BUN and Cr of renal function ≤1.25 times the upper limit of normal value.

6. Have the following cardiac function conditions: ecg examination did not indicate any acute myocardial infarction, arrhythmia or atrioventricular block of degree I or above; Centerless incomplete function; No active rheumatic heart disease; There was no indication of cardiac enlargement on chest radiograph or physical examination.

(7) The patient had a qualified allogeneic hematopoietic stem cell transplantation donor, including haploid, myeloma and sibling.

8) The patient and its legal client have the desire and requirement for hematopoietic stem cell transplantation, and sign the informed consent, and are willing to and abide by the treatment plan, follow-up plan, laboratory examination, etc.

9) The donor meets the donation requirements-

Exclusion Criteria:

1. There are any contraindications for allogeneic hematopoietic stem cell transplantation.
2. Ph+ acute lymphoblastic leukemia
3. Serious damage of important organ functions, such as respiratory failure, heart failure, decompensated liver insufficiency, renal insufficiency, etc.
4. Pregnant or lactating women.
5. Those who are undergoing clinical trials of other drugs.
6. Patients suffering from other serious acute or chronic physical or mental diseases, or abnormal laboratory examination, which may affect the administration of study drugs and the researchers' judgment of the condition and interpretation of the test results, are not suitable to participate in the clinical trial.
7. The donor does not fit the conditions of the donor.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: conditioning regimen with Malilane,cyclophosphamide and fludarabine; Malilane 3.2mg/kg/d *4d (-5,-4,-3,-2day) cyclophosphamide 25mg/kg/d*4d (-9-8,-7,-6 day) fludarabine 30mg/m2/d*4d (-9-8,-7,-6 day) Donor stem cells will be transfused at 0 days.	Drug: Fludarabine; The combination of fludarabine and cyclophosphamide has synergistic effect, which can better kill B lymphocyte, and can enhance the killing effect of pretreatment regimen on B lymphocyte tumor.; Other Names: Malilane and cyclophosphamide
ACTIVE_COMPARATOR: conditioning regimen with Malilane and cyclophosphamide; malilane 3.2mg/kg *4d (-5,-4,-3,-2day) cyclophosphamide 50mg/kg/d*2d (-2,-1day) Donor stem cells will be transfused at 0 days.	Drug: Fludarabine; The combination of fludarabine and cyclophosphamide has synergistic effect, which can better kill B lymphocyte, and can enhance the killing effect of pretreatment regimen on B lymphocyte tumor.; Other Names: Malilane and cyclophosphamide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RFS	Relapse-free survival	one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS (OS).	overall survival	one year
RR	relapse rate	one year
AE	adverse event	one year

Collaborators and Investigators

• Sponsor: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
• Investigators: Principal Investigator: Xianmin Song, MD, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): May 15, 2022
• Primary Completion (ANTICIPATED): November 30, 2023
• Study Completion (ANTICIPATED): December 30, 2025

Study Registration Dates

• First Submitted: May 3, 2022
• First Submitted That Met QC Criteria: May 13, 2022
• First Posted (ACTUAL): May 18, 2022

Study Record Updates

• Last Update Posted (ACTUAL): May 18, 2022
• Last Update Submitted That Met QC Criteria: May 13, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Fludarabine
• Other Study ID Numbers: SHSYXY-B-ALL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No