Phase 1 Study of Chemotherapy Plus HLA-mismatched GPBMC Infusion Bridging to Allo-HSCT for R/R Leukemia

NCT ID: NCT07297173

Last Updated: 2025-12-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

5 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-12-01

Study Completion Date

2030-12-01

Brief Summary

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This is a Phase 1 clinical study designed to evaluate the safety, tolerability, and preliminary efficacy of chemotherapy combining with HLA-mismatched G-CSF mobilized peripheral blood mononuclear cell (GPBMC) infusion as a bridging therapy to allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with relapsed and refractory (R/R) leukemia.

Detailed Description

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Eligible patients will firstly receive chemotherapy combining with infusion of HLA-mismatched GPBMCs with the aim to reduce leukemia burden. Secondly, they will receive allo-HSCT per protocol. GPBMCs used in the first-step infusion will be derived from a sibling or unrelated donor, and GPBMCs used in the allo-HSCT procedure will be derived from an alternative donor, or the same donor (haploidentical/matched sibling/HLA 9-10 loci matched unrelated) as in the first step. The primary endpoint is the incidence of treatment-related adverse events (AEs) within 100 days post allo-HSCT, including graft-versus-host disease (GVHD), infection, organ dysfunction, and hematological toxicity. Secondary endpoints include overall survival (OS) at 1 and 2 years, progression-free survival (PFS), and graft-versus-host disease-free, relapse-free survival (GRFS).

Conditions

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Relapsed Leukemia Refractory Leukemia

Keywords

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HLA-mismatched GPBMC allo-HSCT relapsed leukemia refractory leukemia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort 1

This cohort includes patients with relapsed and refractory leukemia. Patients firstly receive chemotherapy per center standard, followed by HLA-mismatched GPBMC infusion. Secondly, patients receive HLA-matched sibling/haploidentical/unrelated HSCT.

Group Type EXPERIMENTAL

Chemotherapy

Intervention Type PROCEDURE

Available chemotherapy regimens include but not limited to FLAG (fludarabine, cytarabine, G-CSF), DAV (daunorubicin, cytarabine, venetoclax), IAV (idarubicin, cytarabine, venetoclax), VDCP (vincristine, daunorubicin, cyclophosphamide, prednisone), hyper-CVAD A (cyclophosphamide, vincristine, doxorubicin, dexamethasone), FC (fludarabine and cyclophosphamide), et al.

HLA-mismatched GPBMC infusion

Intervention Type BIOLOGICAL

HLA-mismatched GPBMCs are infused following chemotherapy.

Allogeneic Stem Cell Transplantation

Intervention Type PROCEDURE

Patients receive conditioning including but not limited to fludarabine, cyclophosphamide, antithymocyte globulin (ATG), and total body irradiation (TBI). HLA-matched sibling/haploidentical/unrelated GPBMCs are infused at day 0. Post-transplant cyclophosphamide, tacrolimus/cyclosporin, and mycophenolate mofetil are administered as graft-versus-host disease prophylaxis.

Interventions

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Chemotherapy

Available chemotherapy regimens include but not limited to FLAG (fludarabine, cytarabine, G-CSF), DAV (daunorubicin, cytarabine, venetoclax), IAV (idarubicin, cytarabine, venetoclax), VDCP (vincristine, daunorubicin, cyclophosphamide, prednisone), hyper-CVAD A (cyclophosphamide, vincristine, doxorubicin, dexamethasone), FC (fludarabine and cyclophosphamide), et al.

Intervention Type PROCEDURE

HLA-mismatched GPBMC infusion

HLA-mismatched GPBMCs are infused following chemotherapy.

Intervention Type BIOLOGICAL

Allogeneic Stem Cell Transplantation

Patients receive conditioning including but not limited to fludarabine, cyclophosphamide, antithymocyte globulin (ATG), and total body irradiation (TBI). HLA-matched sibling/haploidentical/unrelated GPBMCs are infused at day 0. Post-transplant cyclophosphamide, tacrolimus/cyclosporin, and mycophenolate mofetil are administered as graft-versus-host disease prophylaxis.

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* Age \>=15 years, male or female, non-limited by race or ethnicity.
* Confirmed diagnosis of R/R leukemia and risk stratification according to the World Health Organization (WHO) 5th edition classification, based on histopathology and cytogenetics.
* Adequate hepatic function including alanine transaminase (ALT) and aspartate aminotransferase (AST )\<= 3 × upper limit of normal(ULN), and total bilirubin \<= 1.5 × ULN.
* Adequate renal function including serum creatinine \<= 2 × ULN or CrCl\>= 40mL/min.
* LVEF measured by echocardiogram is within the normal range (LVEF \> 50%).
* The subject must have one HLA mismatched donor who is \>= 18 years old to provide GPBMCs for the first-step infusion. If this donor is not qualified as an allo-HSCT donor, the subject must also have another donor who is \>= 18 years old and qualified as allo-HSCT donor (i.e., matched sibling, 9-10/10 loci matched unrelated, or haploidentical). In addition, the donor voluntarily donates hematopoietic stem cells and signs the consent form. Each subject (or his/her legal representatives) must sign the Informed Consent Form (ICF), indicating that he/she understands the purpose and procedures of research, and is willing to participate in research.

Exclusion Criteria

* Uncontrolled infection or hemorrhage.
* Cardiovascular disease with clinical significance, such as uncontrolled or highly symptomatic cardiac arrhythmias, congestive heart failure, or myocardial infarction within 6 months prior to screening, or New York Heart Association (NYHA) function class 3 (moderate) or class 4 (severe) heart disease.
* Uncontrolled autoimmune disease or requiring immunosuppression treatment.
* History of severe blood infusion reaction.
* Nursing women, women of childbearing potential with positive urine pregnancy test, or women of childbearing potential who are not willing to maintain adequate contraception.
* Psychiatric disorder or cognitive impairment that in the researcher's judgment would make the subject not likely to adhere to the protocol requirements.
* Major surgery within 4 weeks prior to enrollment.
* Life-threatening illness other than leukemia or uncontrolled intercurrent illness.
Minimum Eligible Age

15 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Beijing 302 Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bo Cai, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Hematology, the Fifth Medical Center of Chinese PLA General Hospital

Locations

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Department of Hematology, the Fifth Medical Center of Chinese PLA General Hospital

Beijing, , China

Site Status RECRUITING

Countries

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China

Central Contacts

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Bo Cai, MD

Role: CONTACT

Phone: +861066947168

Email: [email protected]

Yangyang Lei, MD

Role: CONTACT

Phone: +861066947180

Email: [email protected]

Facility Contacts

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Bo Cai, MD

Role: primary

Yangyang Lei, MD

Role: backup

Other Identifiers

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Allo-GPBMC to Allo-HSCT

Identifier Type: -

Identifier Source: org_study_id