Risk-ADAPTed Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation

University of California Irvine (UCI)

Status and phase: Enrolling; Phase 2

Conditions: Allogeneic Hematopoietic Stem Cell Transplantation; Allogeneic Stem Cell Transplantation; Hematologic Malignancies

Treatments: Drug: Fludarabine; Radiation: Total Body Irradiation; Drug: Melphalan

Study type: Interventional

Funder types: Other

Identifiers

NCT06028828

UCI 21-90 (Other Identifier)

3095 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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60 participants in 1 patient group

Patients with AML, ALL, MDS, CML, NHL, HD, CLL requiring AHSCT

Experimental group

Description:

Patients will be treated with allogeneic stem cell transplantation (AHSCT) using fludarabine, melphalan and total body irradiation (TBI) conditioning with different melphalan and TBI doses based on their Hematopoietic Cell Transplant - Composite Risk (HCT-CR), age, and Karnofski performance status (KPS).

Treatment:

Drug: Melphalan

Drug: Fludarabine

Radiation: Total Body Irradiation