Clinical trial NCT06028828: Risk-ADAPTed Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation
Official title: Risk-ADAPTed Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation (ADAPT)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Allogeneic Hematopoietic Stem Cell Transplantation
Allogeneic Stem Cell Transplantation
Hematologic Malignancies
Keywords: Allogeneic Hematopoietic Stem Cell Transplantation
Allogeneic Stem Cell transplantation
AHSCT
Hematologic malignancies
Melphalan
Hematopoietic stem cell transplant -composite risk
Lead sponsor: University of California, Irvine
Sponsor class: OTHER
First posted: 2023-09-08
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a prospective, single-arm, phase II study. Patients will be treated with an allogeneic stem cell transplantation (AHSCT) using fludarabine, melphalan and total body irradiation (TBI) conditioning with different melphalan and TBI doses based on patient- and disease-related risk.

Detailed description: Eligible patients will receive an allogeneic stem cell transplantation using a combination of fludarabine, melphalan and total body irradiation (TBI) conditioning regimen and post-transplant high dose cyclophosphamide (PTCY), tacrolimus and mycophenolate mofetil (MMF) for graft-versus-host prophylaxis.

Melphalan and TBI doses will be tailored based on the Hematopoietic Stem Cell Transplant- Composite Risk (HCT-CR), age and Karnofski performance status (KPS). Melphalan dose ranges from 100 -140 mg/m2 while TBI dose ranges from 2-5 Gy.

All patients will be monitored for safety and efficacy up to 2 years post-transplantation.

Eligibility criteria: Inclusion Criteria:

1. Male or female aged 18-70 years
2. Diagnosis of AML, ALL, MDS, CML, NHL, HD, CLL requiring AHSCT
3. Has an HLA-matched related (MRD), HLA-matched unrelated (MUD), haploidentical (HAPLO) or 1-Ag mismatched unrelated donor (MMUD)
4. Karnofsky performance \>70%
5. Adequate major organ system function as demonstrated by:

   1. Serum creatinine clearance equal or more than 50 ml/min (calculated with Cockroft-Gault formula).
   2. Bilirubin equal or less than 1.5 mg/dl except for Gilbert's disease. ALT or AST equal or less than 200 IU/ml for adults. Conjugated (direct) bilirubin less than 2x upper limit of normal.
   3. Left ventricular ejection fraction equal or greater than 40%.
   4. Diffusing capacity for carbon monoxide (DLCO) equal or greater than 50% predicted corrected for hemoglobin.
6. Ability to understand and the willingness to sign a written informed consent. a. Both men and women and members of all races and ethnic groups are eligible for this trial. Non-English speaking, deaf, hard of hearing and illiterate individuals are eligible for this trial.

Exclusion Criteria:

1. Inability to comply with medical recommendations or follow-up
2. Pregnancy
3. Active/uncontrolled bacterial or viral infection (PI is the final arbiter of this criterion.)
4. Has active CNS or ocular disease involvement within 3 months
5. Patients with primary CNS lymphoma
6. Patients who require modifications of the conditional regimen

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Up to 48 months
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: Up to 48 months
measure: Cumulative incidence of Graft-Versus-Host-Free, relapse-free survival (GRFS)
timeFrame: Up to 48 months
measure: Cumulative incidence of relapse
timeFrame: Up to 48 months
measure: Cumulative incidence of Non-Relapse Mortality (NRM)
timeFrame: Up to 48 months
measure: Cumulative incidence of acute and chronic graft versus host disease (GVHD)
timeFrame: Up to 48 months
measure: Area Under the Curve (AUC) of Melphalan
timeFrame: From melphalan infusion start time to 22 hours after the infusion.
Other outcomes:
Locations:
city: Orange
country: United States
facility: Chao Family Comprehensive Cancer Center, University of California Irvine
state: California
Study officials:
affiliation: Chao Family Comprehensive Cancer Center
name: Stefan O. Ciurea, MD
role: PRINCIPAL_INVESTIGATOR
References: