Acute Lymphoblastic LeukemiaPhase 2NCT05031897

Two Step Haplo With Radiation Conditioning

A Phase 2 study testing Fludarabine, Total-Body Irradiation and Donor Lymphocyte Infusion in people with Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia, run by Thomas Jefferson University at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Adult T-Cell Leukemia/Lymphoma
What is being tested?: Fludarabine, Total-Body Irradiation and Donor Lymphocyte Infusion
Type of treatment: Injection or infusion, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 63 participants
Where: 1 siteUnited States
Study dates: 25 Oct 2021to Apr 2032
Phase: Phase 2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Radiation-based cohort diagnoses:
Acute myeloid leukemia
Acute lymphoid leukemia in remission
Myelodysplasia (MDS)
Chronic lymphocytic leukemia (CLL) with no or minimal lymph node involvement
Multiple myeloma

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Chronic myeloid leukemia
Myelofibrosis
Myeloid malignancy not otherwise specified
Chronic myelomonocytic leukemia
Essential thrombocytopenia or polycythemia vera
T cell leukemia
T cell lymphoma without significant lymph node disease burden
Any hematological malignancy or dyscrasia not cited above in which HSCT is potentially curable
Any patient who has a hematological disease that would normally be treated on a myeloablative study, but is prevented from doing so by factors in their past medical history. Examples are patients with previous treatment with radiation therapy precluding total-body irradiation (TBI), or a past history of myeloablative therapy, precluding a 2nd myeloablative regimen.
Patients must have a donor who is one-haplotype mismatched (number of mismatches in either direction not considered)
Chemotherapy-based cohort diagnoses:
Hodgkin or non-Hodgkin lymphoma
Small lymphocytic lymphoma/CLL
Any other diagnosis in which chemotherapy is thought to be superior to radiotherapy for treatment of the disease
Hematological malignancy in patients who cannot receive > 2 Gy radiation
Aplastic anemia and other non-malignant hematologic dyscrasias
Patients must have a donor who is one-haplotype mismatched (number of mismatches in either direction not considered)
Human leukocyte antigen (HLA) identical cohort diagnoses:
Patients in this group will be treated in parallel to the radiation-based cohort or the chemotherapy-based group based on what category their diagnosis falls into. However, these patients will have HLA identical related donors (one-antigen cross-over event included).
Left ventricular ejection fraction of >= 50%
Diffusion lung capacity of oxygen >= 50% and forced expiratory volume at 1 second >= 50% of predicted corrected for hemoglobin
Serum bilirubin =< 1.8
Aspartate aminotransferase or alanine aminotransferase =< 2.5 x upper limit of normal
Creatinine clearance of >= 60 mL/min
Patients must have adequate Karnofsky performance status (KPS) and Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) scores:
Patients < age 60 years must have a KPS of >= 60% and an HCT-CI score of 5 or less
Patients aged 60 to 65 years must have a KPS of >= 60% and an HCT-CI score of 4 or less
Patients aged 66 to 69 years must have a KPS of 90% and an HCT-CI score of 3 or less
Patients aged 70 years or more must have a KPS of 90% and an HCT-CI score of 2 or less
(Patients with greater than the allowable HCT-CI points for age can be enrolled for trial with approval of the principal investigator (PI) and at least 1 co-investigator (CI) not on the primary care team of the patient). This is an adjustment to account for healthy patients who meet the spirit of this protocol but have histories that result in higher than guideline HCT-CI points. An example is a patient with a solid tumor malignancy in their remote history (adds 3 points to HCT-CI total) where the treatment for the malignancy occurred years to decades before and there has been complete recovery of toxicities
Patients must be willing to use contraception if they have childbearing potential
Patient or patient's guardian is able to give informed consent
Patients should have a life expectancy of >= 6 months for reasons other than their underlying hematologic/oncologic disorder
Patients with evidence of another malignancy, exclusive of a skin cancer that requires only local treatment, should not be enrolled on this protocol
Patients should not be:
Human immunodeficiency virus positive
Have active involvement of the central nervous system with malignancy. This can be documented by a normal neurological exam, magnetic resonance imaging (MRI) of the head, and/or a negative cerebral spinal fluid analysis
Pregnant or breastfeeding

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Usama Gergis, MD contact

215-503-2455

usama.gergis@jefferson.edu

United States1 site, 1 recruiting

Sidney Kimmel Cancer Center at Thomas Jefferson University
Philadephia, Pennsylvania, 19107
Usama Gergis, MD, 215-503-2455, usama.gergis@jefferson.edu
Recruiting

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About this study

Official title: A 2 Step Approach to Haploidentical Transplant Using Radiation-Based Reduced Intensity Conditioning

This phase II clinical trial evaluates whether a modified modality of conditioning reduces treatment-related mortality (TRM) in patients who undergo a hematopoietic stem cell transplant (HSCT) for a hematological malignancy. HSCT is a curative therapy for many hematopoietic malignancies, however this regimen results in higher rates of TRM than other forms of treatment. In recent years, less intense conditioning regimens with radiation and chemotherapy prior to HSCT have been developed. Radiation therapy uses high energy sources to kill cancer cells and shrink tumors while chemotherapy drugs like fludarabine and cyclophosphamide work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This study evaluates whether a two-step approach with lower-intensity regimens of these treatments prior to HSCT reduces the rate of TRM.

Read the detailed description

PRIMARY OBJECTIVE:

To assess the 2 year cumulative incidence of TRM in patients undergoing reduced intensity conditioning (RIC) haploidentical (HI) HSCT in this protocol.

SECONDARY OBJECTIVES:

To assess the 2 year cumulative incidence of relapse in patients undergoing RIC HI HSCT in this protocol.

II. To assess the consistency and pace of engraftment. III. To assess the pace of T cell and B cell immune recovery. IV. To assess the incidence and severity of graft versus host disease (GVHD).

OUTLINE: Patients are assigned to 1 of 2 cohorts.

RADIATION-BASED COHORT: Patients receive fludarabine intravenously (IV) on days -11, -10, -9, and -8, undergo total-body irradiation (TBI) twice a day (BID) on days -10 and -9, undergo donor lymphocyte infusion (DLI) on day -6, and receive cyclophosphamide IV on days -3 and -2. Patients begin tacrolimus and mycophenolate mofetil IV on day -1. Patients then undergo HSCT on day 0. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow biopsy/aspiration, imaging and blood sample collection throughout the study.

CHEMOTHERAPY-BASED COHORT: Patients receive fludarabine IV on days -11, -10, -9, and -8 and melphalan IV on days -10 and -9. Patients undergo TBI and DLI once on day -6. Patients receive cyclophosphamide IV on days -3 and -2 and begin tacrolimus and mycophenolate mofetil on day -1. Patients undergo HSCT on day 0. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow biopsy/aspiration, imaging and blood sample collection throughout the study.

After completion of study treatment, patients are followed for 2 years.

Conditions: Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Adult T-Cell Leukemia/Lymphoma, Aplastic Anemia, Chronic Lymphocytic Leukemia, Chronic Myeloid Leukemia, BCR-ABL1 Positive
Being tested: Fludarabine, Total-Body Irradiation, Donor Lymphocyte Infusion, Cyclophosphamide, Tacrolimus
Medical subject headings: Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Anemia, Aplastic, Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia, Myelomonocytic, Chronic, Thrombocythemia, Essential

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

FludarabineDrug
Also called 2-Fluoro-9-beta-arabinofuranosyladenine, 2-Fluorovidarabine, 21679-14-1, 9-Beta-D-arabinofuranosyl-2-fluoro-9H-purin-6-amine
Given IV
Total-Body IrradiationRadiation
Also called SCT_TBI, TBI, TOTAL BODY IRRADIATION, Whole Body
Undergo TBI
Donor Lymphocyte InfusionProcedure or surgery
Also called DLI, Donor Leukocyte Infusion
Undergo DLI
CyclophosphamideDrug
Also called (-)-Cyclophosphamide, 1-bis(2-chloroethyl)-amino-1-oxo-2-aza-5-oxaphosphoridin monohydrate, 2-[bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate, 2-[bis(b-chloroethyl)amino]-1-oxa-3-aza-2-phosphacyclohexane-2-oxide monohydrate
Given IV
TacrolimusDrug
Also called 109581-93-3, FK 506, FK-506, FK506
Given IV
Mycophenolate MofetilDrug
Also called 115007-34-6, 128794-94-5, Cellcept, MMF
Given IV
Hematopoietic Cell TransplantationProcedure or surgery
Also called HCT, Hematopoietic Stem Cell Infusion, HEMATOPOIETIC STEM CELL TRANSPLANT, Hematopoietic Stem Cell Transplantation
Undergo HSCT
MelphalanDrug
Also called 148-82-3, 4-[bis(2-chloroethyl)amino]-L-phenylalanine, Alanine Nitrogen Mustard, CB-3025
Given IV
Bone Marrow Aspiration and BiopsyProcedure or surgery
Undergo bone marrow aspiration/ biopsy
Diagnostic ImagingProcedure or surgery
Also called Medical Imaging
Undergo diagnostic imaging
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection
Undergo blood sample collection

Study groups in NCT05031897
Study group	Role	What they receive
Arm 1: Radiation-Based Cohort (fludarabine, TBI, infusion)	Experimental	Patients receive fludarabine IV on days -11, -10, -9, and -8, undergo TBI BID on days -10 and -9, undergo DLI on day -6, and receive cyclophosphamide IV on days -3 and -2. Patients begin tacrolimus and mycophenolate mofetil IV on day -1. Patients then undergo HSCT on day 0. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow biopsy/aspiration, imaging and blood sample collection throughout the study. Receives: Drug: Fludarabine; Radiation: Total-Body Irradiation; Procedure: Donor Lymphocyte Infusion; Drug: Cyclophosphamide; Drug: Tacrolimus; Drug: Mycophenolate Mofetil; Procedure: Hematopoietic Cell Transplantation; Procedure: Bone Marrow Aspiration and Biopsy; Procedure: Diagnostic Imaging; Procedure: Biospecimen Collection
Arm 2: Chemotherapy-Based Cohort (fludarabine, melphalan, TBI)	Experimental	Patients receive fludarabine IV on days -11, -10, -9, and -8 and melphalan IV on days -10 and -9. Patients undergo TBI and DLI once on day -6. Patients receive cyclophosphamide IV on days -3 and -2 and begin tacrolimus and mycophenolate mofetil on day -1. Patients undergo hematopoietic stem cell transplant on day 0. Patients undergo bone marrow biopsy/aspiration, imaging and blood sample collection throughout the study. Receives: Drug: Fludarabine; Radiation: Total-Body Irradiation; Procedure: Donor Lymphocyte Infusion; Drug: Cyclophosphamide; Drug: Tacrolimus; Drug: Mycophenolate Mofetil; Procedure: Hematopoietic Cell Transplantation; Drug: Melphalan; Procedure: Bone Marrow Aspiration and Biopsy; Procedure: Diagnostic Imaging; Procedure: Biospecimen Collection
Arm 3: HLA- Identical cohort (radiation-based or chemotherapy-based conditioning)	Experimental	This group (HLA- Identical cohort), which is expected to be small, can undergo HSCT with radiation-based or chemotherapy-based conditioning. Due to small numbers of patients with available HLA identical related donors, this third, descriptive arm is included so that this group, too small in number for a free-standing study, are treated on clinical trial. This is also a separate arm of the study and the outcome of patients treated on this arm will be analyzed descriptively without statistical comparison or power analysis. Receives: Drug: Fludarabine; Radiation: Total-Body Irradiation; Procedure: Donor Lymphocyte Infusion; Drug: Cyclophosphamide; Drug: Tacrolimus; Drug: Mycophenolate Mofetil; Procedure: Hematopoietic Cell Transplantation; Drug: Melphalan; Procedure: Bone Marrow Aspiration and Biopsy; Procedure: Diagnostic Imaging; Procedure: Biospecimen Collection

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants Who Experience Treatment-Related Mortality (TRM)
TRM is defined as death without evidence of recurrent disease in the 2 year period post HSCT. Summarized using Kaplan-Meier curves and the respective Kaplan-Meier estimates of the 2-year event rate are reported as well as their 95% confidence intervals.
Measured: At 2 years post hematopoietic stem cell transplant (HSCT)

Secondary outcomes (4)

Development of relapsed disease
Relapse is measured by evidence of recurrent disease in the blood, marrow, or lymph nodes. Summarized using Kaplan-Meier curves and the respective Kaplan-Meier estimates of the 2-year event rate are reported as well as their 95% confidence intervals.
Measured: Up to 2 years
Engraftment
Measure by chimerism studies of the blood and marrow at multiple time points after the HSCT. Chimerism refers to the percentage of donor cells in the hematopoietic system of the patient post HSCT. Reported using mean and standard deviations.
Measured: Up to 2 years
Immune reconstitution
Evaluated by T-cell recovery and B-cell recovery. Assessed by the quantitative measurement of CD3/4 and CD3/8 cells and immunoglobulin levels in the blood at multiple time points post HSCT. CD3/4 and CD3/8 counts are measured by an immune reconstitution panel and immunoglobulin levels are measured by a quantitative immunoglobulin assay. Reported using mean and standard deviations
Measured: Up to 2 years
Incidence and degree of graft versus host disease (GVHD) after HSCT
Assessment includes presence and degree of skin rash, presence and amount of diarrhea, and/or abnormal liver function test. Summarized using Kaplan-Meier curves and the respective Kaplan-Meier estimates of the 2-year event rate are reported as well as their 95% confidence intervals.
Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

25 Oct 2021Apr 2032

First posted2 Sep 2021
Study start25 Oct 2021
Primary completionApr 2032 (estimated)
Study completionApr 2032 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 63 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05031897
Sponsor's protocol ID: 21D.466
Other IDs: JT 15545
Status last verified: Oct 2025
First submitted: 31 Aug 2021
Last updated: 30 Oct 2025
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No