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Acute Myeloid Leukemia With FLT3/ITD MutationPhase 2NCT01760655

Reduced-Intensity Conditioning Before Donor Stem Cell Transplant in With High-Risk Hematologic Malignancies

A Phase 2 study testing Fludarabine phosphate, Busulfan and Total-Body Irradiation in people with Acute Myeloid Leukemia With FLT3/ITD Mutation and Acute Myeloid Leukemia With Gene Mutations, run by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase II trial studies reduced-intensity conditioning before donor stem cell transplant in treating patients with high-risk hematologic malignancies. Giving low-doses of chemotherapy and total-body irradiation before a donor stem cell transplant helps stop the growth of cancer cells. Read more about this study

Who is it for?
Any age
What is being tested?
Fludarabine phosphate, Busulfan and Total-Body Irradiation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
62 participants
Where
1 siteUnited States
Study dates
24 Dec 2012to 5 Dec 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • By definition, patients with hematological malignancies or dyscrasias that require HSCT as part of cure-directed therapy are by definition high-risk and can be treated on this protocol; examples of high risk patients include but are not limited to:
  • Acute myeloid leukemia with high risk features as defined by:
  • Age greater than or equal to 60
  • Secondary acute myeloid leukemia (AML) (prior therapy or hematologic malignancy)
  • Normal cytogenetics but fms-related tyrosine kinase 3 (FLT3)/internal tandem duplication (ITD) positive
  • Any relapse or primary refractory disease
Show all 32Show fewer
  • Greater than 3 cytogenetic abnormalities or any one of the following cytogenetic abnormalities: -5/del(5q), -7/del(7q), Abn(9q), (11q), (3q), (21q), (17p), t(6;9), t(6;11), t(11;19), +8, del(12p), inv(3), t(10;11), -17, 11q 23
  • Any single autosomal monosomy
  • Acute lymphoid leukemia in 1st or 2nd morphological remission; ALL with any morphological evidence of disease will not be eligible
  • Myelodysplasia (MDS) other than refractory anemia (RA), refractory anemia with rare sideroblasts (RARS), or isolated 5q- syndrome subtypes
  • Hodgkin's or Non-Hodgkin's lymphoma in 2nd or greater remission or with persistent disease
  • Myeloma with evidence of persistent disease after front-line therapy
  • Chronic myeloid leukemia (CML) resistant to signal transducer inhibitor (STI) therapy
  • Myelofibrosis and chronic myelomonocytic leukemia (CMML)
  • Essential thrombocytopenia or polycythemia vera with current or past evidence of evolution to acute leukemia
  • Patients with chronic lymphocytic leukemia (CLL), follicular non-Hodgkin lymphoma (NHL), or other lymphoid malignancies who have highly adverse cytogenetics (such as p53 deletion), are chemo-insensitive, are not responsive to highly effective novel treatments such as chimeric antigen receptor T-lymphocytes (CART) or Ibrutinib, or who have transformed disease
  • Any hematological malignancy not cited above which is thought to be high-risk with increased chance of post HSCT relapse
  • Any patient who has an aggressive 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 TBI, or a past history of myeloablative therapy, precluding a 2nd myeloablative regimen
  • Patients with aplastic anemia may be treated on this protocol, with outcomes reported descriptively
  • Patients must have a related donor who is at least a 2-4/8 antigen mismatch at the human leukocyte antigen (HLA)-A; B; C; DR loci; patients with only a 1 out of 8 mismatch in the GVH direction will be classified in the matched related category
  • Left ventricular end diastolic function (LVEF) of >= 50%
  • Diffusion lung capacity of oxygen (DLCO) >= 50% of predicted corrected for hemoglobin
  • Serum bilirubin =< 1.8
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 x upper limit of normal
  • Creatinine clearance of >= 60 mL/min
  • Patients < age 60 years must have a Karnofsky performance status (KPS) of >= 80% and a hematopoietic cell transplant comorbidity index (HCT-CI) score of 5 or less
  • Patients aged 60 to 65 years must have a KPS of >= 80% 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 [Co-I] 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

Who cannot join

  • Human immunodeficiency virus (HIV) positive
  • Active involvement of the central nervous system with malignancy; this can be documented as a normal neurological exam and/or a negative cerebrospinal fluid (CSF) analysis
  • Pregnancy
  • Patients with life expectancy of =< 6 months for reasons other than their underlying hematologic/oncologic disorder
  • Patients who have received alemtuzumab or ATG within 8 weeks of the transplant admission
  • Patients with evidence of another malignancy, exclusive of a skin cancer that requires only local treatment, should not be enrolled on this protocol

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

Other trials in United States

About this study

Official title: A Two Step Approach to Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation for High Risk Hematologic Malignancies

This phase II trial studies reduced-intensity conditioning before donor stem cell transplant in treating patients with high-risk hematologic malignancies. Giving low-doses of chemotherapy and total-body irradiation before a donor stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) before the transplant may help increase this effect.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To compare the rate of disease-free survival (DFS) at 1 year post hematopoietic stem cell transplant (HSCT) in patients undergoing HSCT treated on this successor Thomas Jefferson University (TJU) 2 Step reduced intensity conditioning (RIC) haploidentical regimen and compare it with that of the initial 2 Step RIC regimen.

SECONDARY OBJECTIVES:

  1. To assess the 100 day regimen-related mortality (RRM) in patients undergoing HSCT on this treatment protocol.

II. To determine the incidence and severity of graft-versus-host disease (GVHD) in patients undergoing treatment on this regimen.

III. To evaluate engraftment rates and lymphoid reconstitution in patients treated on this trial.

IV. To assess overall survival at 1 and 3 years past HSCT in patients treated on this trial.

OUTLINE:

REDUCED INTENSITY CONDITIONING: Patients receive fludarabine phosphate intravenously (IV) on days -15 to -12, busulfan IV on days -14 to -13, donor lymphocyte infusion (DLI) on day -6, and cyclophosphamide IV on days -3 and -2. Patients also undergo total-body irradiation (TBI) on day -10.

TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant (PBSCT) on day 0.

GVHD PROPHYLAXIS: Patients receive tacrolimus IV on days -1 to 42 followed by taper and mycophenolate mofetil IV twice daily (BID) on days -1 to 28.

After completion of study treatment, patients are followed up periodically.

Being tested
Fludarabine phosphate, Busulfan, Total-Body Irradiation, Therapeutic Allogeneic Lymphocytes, Cyclophosphamide
Medical subject headings
Anemia, Aplastic, Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia, Myelomonocytic, Chronic, Lymphoma, Follicular, Hodgkin Disease, Myelodysplastic Syndromes, Primary Myelofibrosis

What participants receive

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

  • Fludarabine phosphateDrug

    Also called 2-F-ara-AMP, 75607-67-9, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-

    Given IV

  • BusulfanDrug

    Also called 1, 4-Bis[methanesulfonoxy]butane, 1,4-Bis(methanesulfonoxy)butane, 1,4-Bitanediol Dimethanesulfonate Esters, 1,4-Butanediol Dimethylsulfonate

    Given IV

  • Total-Body IrradiationRadiation

    Also called TBI, SCT_TBI, TOTAL BODY IRRADIATION, Whole Body

    Undergo TBI

  • Therapeutic Allogeneic LymphocytesBiological

    Also called Allogeneic Lymphocytes

    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

  • Allogeneic Hematopoietic Stem Cell TransplantationProcedure or surgery

    Also called Allogeneic, Allogeneic Hematopoietic Cell Transplantation, allogeneic stem cell transplantation, HSC

    Undergo allogeneic PBSCT

  • Peripheral Blood Stem Cell TransplantationProcedure or surgery

    Also called PBPC transplantation, PBSCT, Peripheral Blood, Peripheral Blood Progenitor Cell Transplantation

    Undergo allogeneic PBSCT

  • TacrolimusDrug

    Also called 109581-93-3, FK 506, Fujimycin, Hecoria

    Given IV

  • Mycophenolate MofetilDrug

    Also called 115007-34-6, 128794-94-5, Cellcept, MMF

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

Study groups in NCT01760655
Study groupRoleWhat they receive
Treatment (RIC and allogeneic PBSCT)ExperimentalREDUCED INTENSITY CONDITIONING: Patients receive fludarabine phosphate IV on days -15 to -12, busulfan IV on days -14 to -13, DLI on day -6, and cyclophosphamide IV on days -3 and -2. Patients also undergo TBI on day -10. TRANSPLANT: Patients undergo allogeneic PBSCT on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV on days -1 to 42 followed by taper and mycophenolate mofetil IV BID on days -1 to 28
Receives: Drug: Fludarabine phosphate; Drug: Busulfan; Radiation: Total-Body Irradiation; Biological: Therapeutic Allogeneic Lymphocytes; Drug: Cyclophosphamide; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Procedure: Peripheral Blood Stem Cell Transplantation; Drug: Tacrolimus; Drug: Mycophenolate Mofetil; Other: Laboratory Biomarker Analysis

What is being measured

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

  1. Disease-free Survival (DFS)

    This hypothesis will be rejected if the 95% confidence interval for year DFS rate computed from the estimated Kaplan-Meier survival curves will be entirely above 0.35.

    Measured: 1 year post hematopoietic stem cell transplant (HSCT)

Secondary outcomes (6)

  1. Overall Survival

    Will be analyzed and reported descriptively.

    Measured: 1 year post HSCT

  2. Overall Survival

    Will be analyzed and reported descriptively.

    Measured: 3 years post HSCT

  3. Immune Reconstitution at Day +28

    CD4 and CD8 values at Day +28. Reported as mean (standard deviation).

    Measured: Up to 1 year

  4. Immune Reconstitution at Day +90

    CD4 and CD8 values at Day +90. Reported as mean (standard deviation).

    Measured: Up to 1 year

  5. Incidence and Degree of Graft Versus Host Disease

    The incidence and severity of graft-versus-host disease (GVHD) will be analyzed and reported descriptively. Clinical manifestations including skin rash, diarrhea, and liver function test abnormalities will be assessed. GVHD will be staged using established clinical grading systems: acute GVHD will be graded according to the modified Glucksberg criteria, and chronic GVHD will be graded using the NIH consensus criteria. These grading systems classify GVHD severity based on organ involvement and clinical symptoms. Higher stages or grades reflect more severe disease and are considered worse outcomes.

    Measured: Up to 1 year

  6. Engraftment Rates

    Will be analyzed and reported descriptively.

    Measured: Up to 1 year

Timeline

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

  1. First posted4 Jan 2013 (estimated)
  2. Study start24 Dec 2012
  3. Primary completion15 Apr 2022
  4. Study completion5 Dec 2022

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
62 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01760655
Sponsor's protocol ID
12D.501
Other IDs
JT 2977
Status last verified
Oct 2025
First submitted
2 Jan 2013
Last updated
30 Oct 2025
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Fludarabine phosphate, Busulfan and Total-Body Irradiation in people with Acute Myeloid Leukemia With FLT3/ITD Mutation and Acute Myeloid Leukemia With Gene Mutations, run by Sidney Kimmel Comprehensive Cancer Center at 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 32 inclusion and 6 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: finished, 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?

Yes. Results are posted in the registry (first posted 30 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Disease-free Survival (DFS) (time frame: 1 year 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 NCT01760655.

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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