A Study Comparing Haploidentical Hematopoietic Stem Cell Transplantations (HSCTs) From Young Non-first-degree and Older First-degree Donors in Hematological Malignancies

Zhejiang University

Status and phase

Enrolling

Phase 3

Conditions

Leukemia

Treatments

Drug: Cyclophosphamide

Drug: Mycophenolate Mofetil

Drug: Busulfan

Drug: Cyclosporin A

Drug: Rabbit antithymocyte globulin

Procedure: Allogeneic HSCT

Drug: MTX

Drug: Me-CCNU

Drug: Cytarabine

Study type

Interventional

Funder types

Other

Identifiers

NCT04547049

NFD-001

Details and patient eligibility

About

An open, multi-center, randomized trial comparing haploidentical HSCTs from young non-first-degree and older first-degree donors in hematological malignancies

Full description

This is an open, multi-center, randomized trial comparing the clinical outcomes of haploidentical HSCTs from young non-first-degree and older first-degree donors in hematological malignancies. This study is indicated for patients with hematological malignancies including acute leukemias and MDS who are eligible to haploidentical HSCTs. 2 groups of patients will be enrolled with 88 in each group. The clinical criteria including survival, relapse, transplantation-related mortality will be monitored.

Enrollment

176 estimated patients

Sex

All

Ages

13 to 78 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Patient Inclusion Criteria:

Patient age 13-78 years
Absence of a suitable HLA identical related or unrelated hematopoietic stem cell donor
Absence of a suitable partially HLA-mismatched (haploidentical), first-degree related donor aged between 18 and 50
Presence of both HLA haploidentical young non-first-degree (age ≤ 40) and older first-degree (age >50) donors

Eligible diagnoses:

AML（excluding APL） with at least one of the following:

median- or high- risk according to the WHO prognostic stratification system
failure to achieve CR after 2 cycles of induction chemotherapy
AML arising from MDS or a myeloproliferative disorder, or secondary AML
patients in CR2 or beyond

Mixed-phenotype acute leukemia (MPAL) in morphological remission Acute lymphoblastic leukemia (T or B) in morphological remission

MDS with at least one of the following:

IPSS score of INT-2 or greater
IPSS score of INT-1 with life-threatening cytopenias, including those generally requiring greater than weekly transfusions
- A first allo-HCT
- Adequate end-organ function
- ECOG performance status < 2
- No other contraindications for HSCT
- Signature of the informed consent

Patient Exclusion Criteria

Availability of suitable HLA identical related or unrelated hematopoietic stem cell donors
Availability of suitable partially HLA-mismatched (haploidentical), first-degree related donor aged between 18 and 50
Not the first allo-HCT
Presence of uncontrolled bacterial, viral, or fungal infection
Patients with severe heart, lung, liver and kidney insufficiency
HIV-positive patients
Women of childbearing potential who are pregnant (β-HCG+) or breast feeding
Patients with a psychiatric history
ECOG performance status ≥ 3
Patients with malignancies other than the primary disease
Refusal to sign the informed consent

Donor Inclusion Criteria:

The donor and recipient must be HLA haploidentical
Meets institutional selection criteria and medically fit to donate
Lack of recipient anti-donor HLA antibody

Donor Exclusion Criteria:

The donor and recipient are HLA identical
Has not donated blood products to recipient

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

176 participants in 2 patient groups

Non-first-degree donor

Active Comparator group

Description:

Each patient receive graft from a non-first degree donor aged ≤40 Conditoning regimens are decided by each center accoding to disease risk, patient age \& status, and cormobidity index.The centers are required to use the same principle when treating NFD and FD patients. The used protocol in the current study included: For MAC: use BU-CY-based (described in detail) For RIC: use BUFlu: Drug: Fludarabine 30 mg/m²/kg, administered IV d-10 through d-5. Drug: Busulfan, 3.2 mg/kg/day administered IV day -6 (BU2) or -7 through -5 (BU3). Other conditioning regimen may include: FluMel, TBF, FTM, Cy-TBI, Flu-TBI.

Treatment:

Drug: Cytarabine

Drug: Me-CCNU

Drug: MTX

Procedure: Allogeneic HSCT

Drug: Rabbit antithymocyte globulin

Drug: Cyclosporin A

Drug: Busulfan

Drug: Mycophenolate Mofetil

Drug: Cyclophosphamide

First-degree donor

Active Comparator group

Description:

Each patients receive graft from a first-degree donor aged \>50 Conditoning regimens are decided by each center accoding to disease risk, patient age \& status, and cormobidity index.The centers are required to use the same principle when treating NFD and FD patients. The used protocol in the current study included: For MAC: use BU-CY-based (described in detail) For RIC: use BUFlu: Drug: Fludarabine 30 mg/m²/kg, administered IV d-10 through d-5. Drug: Busulfan, 3.2 mg/kg/day administered IV day -6 (BU2) or -7 through -5 (BU3). Other conditioning regimen may include: FluMel, TBF, FTM, Cy-TBI, Flu-TBI.

Treatment:

Drug: Cytarabine

Drug: Me-CCNU

Drug: MTX

Procedure: Allogeneic HSCT

Drug: Rabbit antithymocyte globulin

Drug: Cyclosporin A

Drug: Busulfan

Drug: Mycophenolate Mofetil

Drug: Cyclophosphamide