NCT01384513 · REGISTRY CONDITION SEARCH

A Two-Step Approach to Reduced Intensity Bone Marrow Transplant for Patients With Hematological 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: 2026-04-15

This phase II trial studies how well reduced intensity donor stem cell transplant works in treating patients with hematologic malignancies. Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. The donated stem cells may also replace the patient's immune cells and help destroy any remaining cancer cells. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft-versus-host disease). Giving tacrolimus and mycophenolate mofetil after the transplant may stop this from happening. Once the donated stem cells begin working, the patient's immune system may see the remaining cancer cells as not belonging in the patient's body and destroy them. Giving an infusion of the donor's white blood cells (donor lymphocyte infusion) may boost 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

Overall Survival (OS) in Patients With Haploidentical Family Donors With Hematological Malignancies in Morphological or Radiographic Remission or With Chemosensitive, Indolent Diseases

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outcome · POSTED

Treatment Related Mortality (TRM)

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outcome · POSTED

Number of Participants With Acute G2-4 and/or Chronic Moderate or Severe GVHD

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outcome · POSTED

Relapse Rate

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outcome · POSTED

Engraftment Rates

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outcome · POSTED

Incidence of Treatment Related Mortality (TRM)

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outcome · POSTED

Relapse Related Mortality

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outcome · POSTED

Lymphoid Reconstitution

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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: 1. Any patient with hematologic or oncologic diagnosis in which allogeneic HSCT is thought to be beneficial, and in whom front-line therapy has already been applied. Patients treated on this protocol will be without morphological evidence of disease (complete remission or "CR"), or if the patient has evidence of disease, the patient must have had at least a good partial response (PR) to the most recent therapy and the disease must be chemoresponsive. 2. Patients treated on this study will have: * Acute leukemia in 1st or 2nd CR * MDS (myelodysplastic syndrome), specific subtypes of RA (refractory anemia) or RARS (refractory anemia with ringed sideroblasts) subtypes. * Hodgkin or Indolent Non-Hodgkin's lymphoma with chemosensitive disease * Myeloma without morphological evidence of disease, or a deep PR to the most recent therapy * Myeloproliferative disorders with at least a PR to current therapy * Aplastic Anemia * A hematological or oncological disease (not listed) that meets the criteria reviewed above (in CR or with a good PR). 3. Patients must have a related donor who is HLA mismatched at 2, 3, or 4 antigens at the HLA-A; B; C; DR loci in the GVHD direction. (Patients with related donors who are HLA identical or are a 1-antigen mismatch may be treated on this therapeutic approach, but will have their outcomes will not be part of the statistical aims of the study (see Summary section). 4. Patients must adequate organ function: * LVEF (Left ventricular end diastolic function) of \>50% * DLCO (Diffusing Capacity of the Lung for Carbon Monoxide ) ≥50% of predicted corrected for hemoglobin * Adequate liver function as defined by a serum bilirubin \<1.8, AST or ALT \< 2.5X upper limit of normal * Creatinine Clearance of ≥ 60 mL/min 5. Performance status ≥ 80% (TJU Karnofsky) for patients ≥ 60 years old or ≥70% for patients \< 60 years old. 6. HCT-CI Score ≤ 4 points for patients ≥ 60 years old or ≤ 5 points for patients \< 60 years old. • 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 \>= 80% and an 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 7. Patients must be willing to use contraception if they have childbearing potential 8. Able to give informed consent Exclusion Criteria: * Human immunodeficiency virus (HIV) positive * Active involvement of the central nervous system with malignancy * Inability to obtain informed consent * Pregnancy * Patients with life expectancy of =\< 6 months for reasons other than their underlying hematologic/oncologic disorder * Patients who have received alemtuzumab or anti-thymocyte globulin (ATG) within 8 weeks of the transplant admission; (documented by the absence of these agents in the medical record) * 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
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
REDUCED INTENSITY CONDITIONING: Patients receive fludarabine phosphate IV over 60 minutes on days -11 to -8 and busulfan IV over 3 hours on days -10 to -9. Patients undergo TBI on day -6. Patients also receive cyclophosphamide IV over 2 hours on days -3 and -2. TRANSPLANTATION: Patients undergo DLI on day -6 and CD-34+ allogeneic PBSCT on day 0. GVHD PROPHYLAXIS: Beginning on day -1, patients receive tacrolimus IV or PO with taper beginning on day 42. Patients also receive mycophenolate mofetil IV BID on days -1 to 28.
intervention Names
Drug: Fludarabine
Drug: Busulfan
Radiation: Total Body Irradiation (TBI)
Biological: Donor Lymphocyte Infusion (DLI)
Drug: Cyclophosphamide (CY)
Drug: Tacrolimus
Drug: Mycophenolate mofetil
Device: Allogeneic hematopoietic stem cell transplantation
Procedure: Peripheral blood stem cell transplantation (PBSCT)
label
Treatment (Allogeneic PBSCT)
type
EXPERIMENTAL

interventions

arm Group Labels
Treatment (Allogeneic PBSCT)
description
Given IV
name
Fludarabine
other Names
fludarabine phosphate
Fludara
type
DRUG
arm Group Labels
Treatment (Allogeneic PBSCT)
description
Given IV
name
Busulfan
other Names
Myleran
Busulfex IV
type
DRUG
arm Group Labels
Treatment (Allogeneic PBSCT)
description
2 Gy administered as part of the conditioning regimen
name
Total Body Irradiation (TBI)
other Names
radiotherapy
type
RADIATION
arm Group Labels
Treatment (Allogeneic PBSCT)
description
Undergo DLI
name
Donor Lymphocyte Infusion (DLI)
other Names
buffy coat fusion
type
BIOLOGICAL
arm Group Labels
Treatment (Allogeneic PBSCT)
description
Given IV
name
Cyclophosphamide (CY)
other Names
Endoxan
Cytoxan
Neosar
Procytox
Revimmune
cytophosphane
type
DRUG
arm Group Labels
Treatment (Allogeneic PBSCT)
description
Given IV or PO
name
Tacrolimus
other Names
FK-506
Fujimycin
type
DRUG
arm Group Labels
Treatment (Allogeneic PBSCT)
description
Given IV
name
Mycophenolate mofetil
other Names
MMF
CellCept
type
DRUG
arm Group Labels
Treatment (Allogeneic PBSCT)
description
Undergo CD34+ allogeneic PBSCT
name
Allogeneic hematopoietic stem cell transplantation
other Names
CliniMACS
type
DEVICE
arm Group Labels
Treatment (Allogeneic PBSCT)
description
Undergo CD34+ allogeneic PBSCT
name
Peripheral blood stem cell transplantation (PBSCT)
other Names
PBPC transplantation
PBSC transplantation
peripheral blood progenitor cell transplantation
transplantation
peripheral blood stem cell
type
PROCEDURE

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 40
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
The primary null hypothesis is that 2 year OS rate is at most 35%. This hypothesis will be rejected if the 95% confidence interval for year OS rate computed from the estimated Kaplan-Meier survival curves will be entirely above 0.35.
measure
Overall Survival (OS) in Patients With Haploidentical Family Donors With Hematological Malignancies in Morphological or Radiographic Remission or With Chemosensitive, Indolent Diseases
time Frame
At 2 years

secondary Outcomes

description
To compare the treatment related mortality rate (TRM) for patients treated on this study to the historical TRM rates of patients undergoing reduced intensity conditioning (RIC) matched-sibling hematopoietic stem cell transplant (HSCT) as reported in the literature
measure
Treatment Related Mortality (TRM)
time Frame
At 2 years
description
The estimates of incidence rates will be presented with corresponding 95% confidence intervals using the exact method
measure
Number of Participants With Acute G2-4 and/or Chronic Moderate or Severe GVHD
time Frame
Assessed up to 2 years
description
Evaluated by estimating Kaplan-Meier survival curves. From these curves, the 95% confidence interval for 2 year rates will be computed.
measure
Relapse Rate
time Frame
At 2 years
description
Hematopoietic engraftment will be defined as: * ANC ≥ 0.5x10e9/L for at least 3 days * Platelet engraftment \>20,000 with no transfusion x 7 days.
measure
Engraftment Rates
time Frame
44 weeks
description
The estimates of incidence rates will be presented with corresponding 95% confidence intervals using the exact method.
measure
Incidence of Treatment Related Mortality (TRM)
time Frame
At 100 days
description
Evaluated by estimating Kaplan-Meier survival curves. From these curves, the 95% confidence interval for 2 year rates will be computed.
measure
Relapse Related Mortality
time Frame
At 2 years
description
To evaluate lymphoid reconstitution in patients treated on the Two Step approach
measure
Lymphoid Reconstitution
time Frame
100 days post-transplant

Full study description

brief Summary: This phase II trial studies how well reduced intensity donor stem cell transplant works in treating patients with hematologic malignancies. Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. The donated stem cells may also replace the patient's immune cells and help destroy any remaining cancer cells. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft-versus-host disease). Giving tacrolimus and mycophenolate mofetil after the transplant may stop this from happening. Once the donated stem cells begin working, the patient's immune system may see the remaining cancer cells as not belonging in the patient's body and destroy them. Giving an infusion of the donor's white blood cells (donor lymphocyte infusion) may boost this effect.
detailed Description: PRIMARY OBJECTIVES: I. To compare the overall survival (OS) rate at 2 years post treatment using the Jefferson 2 step reduced intensity conditioning (RIC) approach in patients with haploidentical family donors with hematological malignancies in morphological or radiographic remission or with chemosensitive, indolent diseases to historical OS rates in similar populations after RIC matched donor HSCT as reported in the literature. SECONDARY OBJECTIVES: I. To compare the treatment-related mortality (TRM) rate at 2 years for patients treated on this study to the historical TRM rates of patients undergoing RIC matched-sibling HSCT as reported in the literature. II. To compare the 2 year relapse rates and relapse related mortality of patients with myeloid diseases to that of patients with lymphoid diseases who are treated on this Thomas Jefferson University (TJU) RIC 2 step approach. III. To determine the incidence and severity of graft-versus-host disease (GVHD) in patients undergoing treated on the TJU RIC 2 step approach. IV. To evaluate engraftment rates and lymphoid reconstitution in patients treated on the TJU RIC 2 step approach. V. To evaluate the incidence of TRM at 100 days in patients treated on the TJU RIC 2 step approach. OUTLINE: REDUCED INTENSITY CONDITIONING: Patients receive fludarabine phosphate intravenously (IV) over 60 minutes on days -11 to -8 and bulsufan IV over 3 hours on days -10 to -9. Patients undergo total body irradiation (TBI) on day -6. Patients also receive cyclophosphamide IV over 2 hours on days -3 and -2. TRANSPLANTATION: Patients undergo donor lymphocyte infusion (DLI) on day -6 and cluster of differentiation (CD)-34+ allogeneic peripheral blood stem cell transplantation (PBSCT) on day 0. GVHD PROPHYLAXIS: Beginning on day -1, patients receive tacrolimus IV or orally (PO) with taper beginning on day 42. Patients also receive mycophenolate mofetil IV twice daily (BID) on days -1 to 28. After completion of study treatment, patients are followed up periodically for 2 years.

Source references