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

Primary Purpose

Allogeneic Hematopoietic Stem Cell Transplantation, Allogeneic Stem Cell Transplantation, Hematologic Malignancies

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Fludarabine
Melphalan
Total Body Irradiation
Sponsored by
University of California, Irvine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Allogeneic Hematopoietic Stem Cell Transplantation focused on measuring Allogeneic Hematopoietic Stem Cell Transplantation, Allogeneic Stem Cell transplantation, AHSCT, Hematologic malignancies, Melphalan, Hematopoietic stem cell transplant -composite risk

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Male or female aged 18-70 years Diagnosis of AML, ALL, MDS, MPN, CML, NHL, HD, CLL requiring AHSCT Has an HLA-matched related (MRD), HLA-matched unrelated (MUD), haploidentical (HAPLO) or 1-Ag mismatched unrelated donor (MMUD) Karnofsky performance >70% Adequate major organ system function as demonstrated by: Serum creatinine clearance equal or more than 50 ml/min (calculated with Cockroft-Gault formula). 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. Left ventricular ejection fraction equal or greater than 40%. Diffusing capacity for carbon monoxide (DLCO) equal or greater than 50% predicted corrected for hemoglobin. 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: Inability to comply with medical recommendations or follow-up Pregnancy Active/uncontrolled bacterial or viral infection (PI is the final arbiter of this criterion.) Has active CNS or ocular disease involvement within 3 months Patients with primary CNS lymphoma Patients who require modifications of the conditional regimen

Sites / Locations

  • Chao Family Comprehensive Cancer Center, University of California IrvineRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

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

Arm 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).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.

Full Information

First Posted
August 31, 2023
Last Updated
September 14, 2023
Sponsor
University of California, Irvine
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1. Study Identification

Unique Protocol Identification Number
NCT06028828
Brief Title
Risk-ADAPTed Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation
Acronym
ADAPT
Official Title
Risk-ADAPTed Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation (ADAPT)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 11, 2023 (Actual)
Primary Completion Date
September 2026 (Anticipated)
Study Completion Date
September 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, Irvine

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Patients with AML, ALL, MDS, MPN, CML, NHL, HD, CLL requiring AHSCT
Arm Type
Experimental
Arm 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).
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Description
Given Day-5, Day-4, Day-3, Day-2
Intervention Type
Drug
Intervention Name(s)
Melphalan
Intervention Description
Given Day-5
Intervention Type
Radiation
Intervention Name(s)
Total Body Irradiation
Other Intervention Name(s)
TBI
Intervention Description
Given Day-1
Primary Outcome Measure Information:
Title
Progression-free survival (PFS)
Description
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.
Time Frame
Up to 48 months
Secondary Outcome Measure Information:
Title
Overall survival (OS)
Description
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.
Time Frame
Up to 48 months
Title
Cumulative incidence of Graft-Versus-Host-Free, relapse-free survival (GRFS)
Description
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.
Time Frame
Up to 48 months
Title
Cumulative incidence of relapse
Description
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.
Time Frame
Up to 48 months
Title
Cumulative incidence of Non-Relapse Mortality (NRM)
Description
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.
Time Frame
Up to 48 months
Title
Cumulative incidence of acute and chronic graft versus host disease (GVHD)
Description
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.
Time Frame
Up to 48 months
Title
Area Under the Curve (AUC) of Melphalan
Description
AUC will be used to determine the pharmacokinetic of melphalan after the infusion on D-5. Data will be summarized using descriptive statistics.
Time Frame
From melphalan infusion start time to 22 hours after the infusion.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female aged 18-70 years Diagnosis of AML, ALL, MDS, MPN, CML, NHL, HD, CLL requiring AHSCT Has an HLA-matched related (MRD), HLA-matched unrelated (MUD), haploidentical (HAPLO) or 1-Ag mismatched unrelated donor (MMUD) Karnofsky performance >70% Adequate major organ system function as demonstrated by: Serum creatinine clearance equal or more than 50 ml/min (calculated with Cockroft-Gault formula). 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. Left ventricular ejection fraction equal or greater than 40%. Diffusing capacity for carbon monoxide (DLCO) equal or greater than 50% predicted corrected for hemoglobin. 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: Inability to comply with medical recommendations or follow-up Pregnancy Active/uncontrolled bacterial or viral infection (PI is the final arbiter of this criterion.) Has active CNS or ocular disease involvement within 3 months Patients with primary CNS lymphoma Patients who require modifications of the conditional regimen
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Chao Family Comprehensive Cancer Center University of California, Irvine
Phone
1-877-827-8839
Email
ucstudy@uci.edu
First Name & Middle Initial & Last Name or Official Title & Degree
University of California Irvine Medical
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stefan O. Ciurea, MD
Organizational Affiliation
Chao Family Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Chao Family Comprehensive Cancer Center, University of California Irvine
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stefan O Ciurea, MD
Phone
877-827-8839
Email
ucstudy@uci.edu

12. IPD Sharing Statement

Learn more about this trial

Risk-ADAPTed Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation

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