NCT01760655 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE2
Status at capture: COMPLETED
Registry last update: 2025-10-30

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Disease-free Survival (DFS)

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outcome · POSTED

Overall Survival

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outcome · POSTED

Overall Survival

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outcome · POSTED

Immune Reconstitution at Day +28

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outcome · POSTED

Immune Reconstitution at Day +90

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outcome · POSTED

Incidence and Degree of Graft Versus Host Disease

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outcome · POSTED

Engraftment Rates

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * 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 * 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 Exclusion Criteria: * 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
healthy Volunteers: false
sex: ALL
std Ages: CHILD
ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
REDUCED 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
intervention Names
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
label
Treatment (RIC and allogeneic PBSCT)
type
EXPERIMENTAL

interventions

arm Group Labels
Treatment (RIC and allogeneic PBSCT)
description
Given IV
name
Fludarabine phosphate
other Names
2-F-ara-AMP
75607-67-9
9H-Purin-6-amine
2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-
2-fluoro-9-(5-O-phosphono-beta-D-arabinofuranosyl)
Beneflur
Fludara
Fludarabine-5'-Monophosphate
SH T 586
type
DRUG
arm Group Labels
Treatment (RIC and allogeneic PBSCT)
description
Given IV
name
Busulfan
other Names
1, 4-Bis[methanesulfonoxy]butane
1,4-Bis(methanesulfonoxy)butane
1,4-Bitanediol Dimethanesulfonate Esters
1,4-Butanediol Dimethylsulfonate
1,4-Di(methanesulfonyloxy)butane
1,4-Di(methylsulfonyloxy)butane
55-98-1
BUS
Bussulfam
Busulfanum
Busulfex
Busulphan
type
DRUG
arm Group Labels
Treatment (RIC and allogeneic PBSCT)
description
Undergo TBI
name
Total-Body Irradiation
other Names
TBI
SCT_TBI
TOTAL BODY IRRADIATION
Whole Body
Whole Body Irradiation
Whole-Body Irradiation
type
RADIATION
arm Group Labels
Treatment (RIC and allogeneic PBSCT)
description
Undergo DLI
name
Therapeutic Allogeneic Lymphocytes
other Names
Allogeneic Lymphocytes
type
BIOLOGICAL
arm Group Labels
Treatment (RIC and allogeneic PBSCT)
description
Given IV
name
Cyclophosphamide
other Names
(-)-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
2-[di(chloroethyl)amino]-1-oxa-3-aza-2-phosphacyclohexane 2-oxide monohydrate
2H-1,3,2-Oxazaphosphorine
2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
6055-19-2
bis(2-chloroethyl)phosphamide cyclic propanolamide ester monohydrate
Bis(2-chloroethyl)phosphoramide cyclic propanolamide ester monohydrate
Carloxan
Ciclofosfamida
type
DRUG
arm Group Labels
Treatment (RIC and allogeneic PBSCT)
description
Undergo allogeneic PBSCT
name
Allogeneic Hematopoietic Stem Cell Transplantation
other Names
Allogeneic
Allogeneic Hematopoietic Cell Transplantation
allogeneic stem cell transplantation
HSC
HSCT
Stem Cell Transplantation
type
PROCEDURE
arm Group Labels
Treatment (RIC and allogeneic PBSCT)
description
Undergo allogeneic PBSCT
name
Peripheral Blood Stem Cell Transplantation
other Names
PBPC transplantation
PBSCT
Peripheral Blood
Peripheral Blood Progenitor Cell Transplantation
PERIPHERAL BLOOD STEM CELL TRANSPLANT
peripheral stem cell support
Peripheral Stem Cell Transplant
peripheral stem cell transplantation
type
PROCEDURE
arm Group Labels
Treatment (RIC and allogeneic PBSCT)
description
Given IV
name
Tacrolimus
other Names
109581-93-3
FK 506
Fujimycin
Hecoria
Prograf
Protopic
type
DRUG
arm Group Labels
Treatment (RIC and allogeneic PBSCT)
description
Given IV
name
Mycophenolate Mofetil
other Names
115007-34-6
128794-94-5
Cellcept
MMF
type
DRUG
arm Group Labels
Treatment (RIC and allogeneic PBSCT)
description
Correlative studies
name
Laboratory Biomarker Analysis
type
OTHER

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 62
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
Disease-free Survival (DFS)
time Frame
1 year post hematopoietic stem cell transplant (HSCT)

secondary Outcomes

description
Will be analyzed and reported descriptively.
measure
Overall Survival
time Frame
1 year post HSCT
description
Will be analyzed and reported descriptively.
measure
Overall Survival
time Frame
3 years post HSCT
description
CD4 and CD8 values at Day +28. Reported as mean (standard deviation).
measure
Immune Reconstitution at Day +28
time Frame
Up to 1 year
description
CD4 and CD8 values at Day +90. Reported as mean (standard deviation).
measure
Immune Reconstitution at Day +90
time Frame
Up to 1 year
description
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.
measure
Incidence and Degree of Graft Versus Host Disease
time Frame
Up to 1 year
description
Will be analyzed and reported descriptively.
measure
Engraftment Rates
time Frame
Up to 1 year

Full study description

brief 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. 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.
detailed Description: PRIMARY OBJECTIVES: I. 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: I. 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.

Source references