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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

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Fludarabine, Total-Body Irradiation and Donor Lymphocyte Infusion
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
Are there results?
Not yet: the study is under way

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
Show all 44Show fewer
  • 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

Other trials in United States

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:

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

SECONDARY OBJECTIVES:

  1. 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.

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 groupRoleWhat they receive
Arm 1: Radiation-Based Cohort (fludarabine, TBI, infusion)ExperimentalPatients 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)ExperimentalPatients 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)ExperimentalThis 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.

  1. 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)

  1. 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

  2. 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

  3. 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

  4. 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.

  1. First posted2 Sep 2021
  2. Study start25 Oct 2021
  3. Primary completionApr 2032 (estimated)
  4. Study completionApr 2032 (estimated)

Resources

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

Questions about this trial

What is this clinical trial studying?

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.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 44 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 30 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Usama Gergis, MD (215-503-2455, usama.gergis@jefferson.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Who Experience Treatment-Related Mortality (TRM) (time frame: At 2 years post hematopoietic stem cell transplant (HSCT)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05031897.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2025.

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Two Step Haplo With Radiation Conditioning | AzTrials