Risk-ADAPTed Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation

Hematologic Malignancies Clinical Trial

— ADAPT  

Official title:

Risk-ADAPTed Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation (ADAPT)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06028828
• Other study ID #: 3095
• Secondary ID: UCI 21-90
• Status: Recruiting
• Phase: Phase 2
• Start date: September 11, 2023
• Est. completion date: September 2027

Study information

• Verified date: March 2024
• Source: University of California, Irvine
• Contact: Chao Family Comprehensive Cancer Center University of California
• Phone: 1-877-827-8839
• Email: ucstudy[@]uci.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: September 2027
• Est. primary completion date: September 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Allogeneic Hematopoietic Stem Cell Transplantation
• Allogeneic Stem Cell Transplantation
• Hematologic Malignancies
• Hematologic Neoplasms
• Neoplasms

Intervention

Drug:
• Fludarabine
Given Day-5, Day-4, Day-3, Day-2
• Melphalan
Given Day-5

Radiation:
• Total Body Irradiation
Given Day-1

Locations

Country	Name	City	State
United States	Chao Family Comprehensive Cancer Center, University of California Irvine	Orange	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, Irvine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS)	PFS is defined as the time from stem cell infusion to time of disease relapse or death from any cause; data for patients who were alive without relapse will be censored at the date of last contact.	Up to 48 months
Secondary	Overall survival (OS)	OS is defined as the time from stem cell infusion until death from any cause. Data of patients who were alive without relapse will be censored at the date of last contact.	Up to 48 months
Secondary	Cumulative incidence of Graft-Versus-Host-Free, relapse-free survival (GRFS)	GRFS is defined as time from stem cell infusion to time of the first event among acute GVHD grades 3-4, extensive chronic GVHD, relapse, and death. Data of patients who are event-free will be censored at the date of last contact.	Up to 48 months
Secondary	Cumulative incidence of relapse	Relapse is defined as re-occurrence of the disease after stem cell infusion. Cumulative incidence of relapse will be measured from date of stem cell infusion to date of disease relapse. Death without disease relapse is considered a competing risk for relapse. Data of patients who are alive without disease relapse will be censored at the date of last contact.	Up to 48 months
Secondary	Cumulative incidence of Non-Relapse Mortality (NRM)	NRM is defined as death related to AHSCT during continuous complete remission. Cumulative incidence of NRM will be measured from date of stem cell infusion to date of death. Disease relapse is considered a competing risk for NRM. Data of patients who are alive without disease relapse will be censored at the date of last contact.	Up to 48 months
Secondary	Cumulative incidence of acute and chronic graft versus host disease (GVHD)	Acute and chronic GVHD will be measured from date of stem cell infusion to date of the event. Death without GVHD is considered a competing risk for GVHD. Patients who are alive without GVHD will be censored at the date of last contact.	Up to 48 months
Secondary	Area Under the Curve (AUC) of Melphalan	AUC will be used to determine the pharmacokinetic of melphalan after the infusion on D-5. Data will be summarized using descriptive statistics.	From melphalan infusion start time to 22 hours after the infusion.