A Two-Step Approach to Reduced Intensity Bone Marrow Transplant for Patients With Hematological Malignancies

March 26, 2026 updated by: Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University

A Two Step Approach to Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation for Patients With Hematologic Malignancies

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (Allogeneic PBSCT)

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.
Drug: Fludarabine
Given IV
Other Names:
  • Fludara
  • fludarabine phosphate
Drug: Tacrolimus
Given IV or PO
Other Names:
  • Fujimycin
  • FK-506
Drug: Busulfan
Given IV
Other Names:
  • Myleran
  • Busulfex IV
Drug: Mycophenolate mofetil
Given IV
Other Names:
  • CellCept
  • MMF
Biological: Donor Lymphocyte Infusion (DLI)
Undergo DLI
Other Names:
  • buffy coat fusion
Radiation: Total Body Irradiation (TBI)
2 Gy administered as part of the conditioning regimen
Other Names:
  • radiotherapy
Drug: Cyclophosphamide (CY)
Given IV
Other Names:
  • Cytoxan
  • Endoxan
  • Neosar
  • Revimmune
  • Procytox
  • cytophosphane
Device: Allogeneic hematopoietic stem cell transplantation
Undergo CD34+ allogeneic PBSCT
Other Names:
  • CliniMACS
Procedure: Peripheral blood stem cell transplantation (PBSCT)
Undergo CD34+ allogeneic PBSCT
Other Names:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation
  • peripheral blood stem cell

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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.
At 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Treatment Related Mortality (TRM)
Time Frame: At 2 years
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
At 2 years
Relapse Rate
Time Frame: At 2 years
Evaluated by estimating Kaplan-Meier survival curves. From these curves, the 95% confidence interval for 2 year rates will be computed.
At 2 years
Incidence of Treatment Related Mortality (TRM)
Time Frame: At 100 days
The estimates of incidence rates will be presented with corresponding 95% confidence intervals using the exact method.
At 100 days
Relapse Related Mortality
Time Frame: At 2 years
Evaluated by estimating Kaplan-Meier survival curves. From these curves, the 95% confidence interval for 2 year rates will be computed.
At 2 years
Lymphoid Reconstitution
Time Frame: 100 days post-transplant
To evaluate lymphoid reconstitution in patients treated on the Two Step approach
100 days post-transplant
Number of Participants With Acute G2-4 and/or Chronic Moderate or Severe GVHD
Time Frame: Assessed up to 2 years
The estimates of incidence rates will be presented with corresponding 95% confidence intervals using the exact method
Assessed up to 2 years
Engraftment Rates
Time Frame: 44 weeks

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.
44 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University

Investigators

  • Principal Investigator: Usama Gergis, MD, Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 4, 2011

Primary Completion (Actual)

November 13, 2020

Study Completion (Actual)

November 16, 2022

Study Registration Dates

First Submitted

June 27, 2011

First Submitted That Met QC Criteria

June 27, 2011

First Posted (Estimated)

June 29, 2011

Study Record Updates

Last Update Posted (Actual)

April 15, 2026

Last Update Submitted That Met QC Criteria

March 26, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 11D.247
  • 2011-31 (CCRRC)
  • JT 1795 (Other Identifier: JeffTrial Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Primary Myelofibrosis

Clinical Trials on Fludarabine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Lithuania

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe