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Hematologic MalignanciesPhase 1/2NCT00429143

A Two-Step Approach to Bone Marrow Transplant Using Cells From A Partially-Matched Relative

A Phase 1/2 study testing Total Body Irradiation (TBI), Donor Lymphocyte Infusion (DLI) and Cyclophosphamide (CY) in people with Hematologic Malignancies, 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

The purpose of this study is to develop a way of treating patients who do not have a completely matched family donor or a readily available unrelated donor with bone marrow transplant by using a partially-matched family donor. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hematologic Malignancies
What is being tested?
Total Body Irradiation (TBI), Donor Lymphocyte Infusion (DLI) and Cyclophosphamide (CY)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
27 participants
Where
1 siteUnited States
Study dates
Jan 2006to Jun 2010
Phase
Phase 1/2
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Any patient with a hematologic or oncologic diagnosis in which allogeneic HSCT is thought to be beneficial, and in whom front-line therapy has already been applied.
  • Patients must have a related donor who is either a one, two or three out of six antigen mismatch at the HLA-A;B;DR loci.
  • Patients without a well-matched unrelated donor or those who have a disease status that precludes a wait for an identified unrelated donor.
  • Patients must adequate organ function:
  • LVEF of >45%
  • FVC or FEV1 >45% of predicted
Show all 11Show fewer
  • Adequate liver function as defined by a serum bilirubin <1.8, AST or ALT < 2.5X upper limit of normal
  • Serum creatinine < 2.0 mg/dl or creatinine clearance of > 40 ml/min
  • Performance status > 60% (Karnofsky)
  • Patients must be willing to use contraception if they have childbearing potential
  • Able to give informed consent

Who cannot join

  • An eligible HLA-identical sibling donor.
  • Performance status < 60% (Karnosfsky)
  • HIV positive
  • Active involvement of the central nervous system with malignancy
  • Psychiatric disorder that would preclude patients from signing an informed consent
  • Pregnancy
  • Patients with life expectancy of < 6 months for reasons other than their underlying hematologic/oncologic disorder.

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 Allogeneic Hematopoietic Stem Cell Transplantation for Hematologic Malignancies From HLA Partially-Matched Related Donors

The purpose of this study is to develop a way of treating patients who do not have a completely matched family donor or a readily available unrelated donor with bone marrow transplant by using a partially-matched family donor. Patients receiving this type of transplant will receive chemotherapy and/or radiation to treat their disease. They will also receive their donor's cells in 2 parts. During the first part, the donor's lymphocytes will be exposed to one of the chemotherapy agents to help the patient become tolerant to the lymphocytes. In the second part of the transplant, the patient will receive their donor's stem cells to help recover their peripheral blood counts and establish long-term engraftment. The hypothesis of this study is that in partially-matched allogeneic transplant, there is a defined number of donor T-cells that can be treated and given to the recipient to avoid post-transplant infection without causing severe graft-versus-host disease.

Read the detailed description

Haploidentical hematopoietic stem cell transplant is a life-saving therapy for patients who are without well matched donors. This type of therapy has been associated with poor outcomes in the past due to complications such as infection. The Jefferson 2 Step approach was designed to allow the infusion of an exact dose of tolerized lymphocytes in haploidentical transplant in order to allow for immune reconstitution post transplant to avoid infectious complications while still having acceptable rates of GVHD. In this approach, patients with high-risk hematological malignancies undergo 8 fractions of TBI (12 Gy) followed by an exact dose of donor lymphocytes. The phase I portion of the study determined the optimal dose of lymphocytes. Two days after receiving the donor lymphocytes, the patients receive 2 daily doses of cyclophosphamide. One day after receiving cyclophosphamide, the patients receive stem cell from their donor. Tacrolimus and mycophenylate mofetil are used as GVHD prophylaxis.

Being tested
Total Body Irradiation (TBI), Donor Lymphocyte Infusion (DLI), Cyclophosphamide (CY), Tacrolimus, Mycophenolate Mofetil (MMF)
Keywords
Hematologic Malignancies, Two Step Approach, Haploidentical Transplant
Medical subject headings
Hematologic Neoplasms

What participants receive

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

  • Total Body Irradiation (TBI)Radiation

    Also called TBI, radiotherapy

    TBI twice daily days 6-9 prior to transplant (HSCT)

  • Donor Lymphocyte Infusion (DLI)Biological

    Also called DLI, T cell infusion

    DLI given 6 days prior to transplant (HSCT).

  • Cyclophosphamide (CY)Drug

    Also called CY, Endoxan, Cytoxan, Neosar

    Cyclophosphamide given once daily at 60 mg/kg on days 2 and 3 prior to transplant (HSCT).

  • TacrolimusDrug

    Also called FK-506, fujimycin, Prograf, Advagraf

    Tacrolimus given one day prior to transplant (HSCT).

  • Mycophenolate Mofetil (MMF)Drug

    Also called MMF, CellCept, Myfortic

    MMF given one day prior to transplant (HSCT).

  • Hematopoietic Stem Cell Transplant (HSCT)Biological

    Also called HSCT, stem cell transplant

    CD34+ selected Hematopoietic Stem Cell Transplant (HSCT) is performed. This is the day of transplantation.

Study groups in NCT00429143
Study groupRoleWhat they receive
Haploidentical Allogeneic TransplantationExperimentalPatients undergoing hematopoietic stem cell transplant from a partially matched related donor
Receives: Radiation: Total Body Irradiation (TBI); Biological: Donor Lymphocyte Infusion (DLI); Drug: Cyclophosphamide (CY); Drug: Tacrolimus; Drug: Mycophenolate Mofetil (MMF); Biological: Hematopoietic Stem Cell Transplant (HSCT)

What is being measured

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

  1. Overall Survival of Participants

    To determine overall survival at 6 months post-transplant.

    Measured: 6 months

  2. Optimal Dose of CD3+ Donor Lymphocytes (T-cells) for Consistent Engraftment Without GVHD

    To determine the optimal dose of CD3+ donor lymphocytes required for consistent engraftment without the development of grade III/IV GVHD.

    Measured as CD3+ donor lymphocytes given as n x 10^8/kg.

    "n" was found to be 2 and was found to be the optimal dose and was the only dose given.

    Measured: 6 months

Secondary outcomes (3)

  1. Engraftment Rates

    To assess hematopoietic engraftment rates.

    Measured: 6 months

  2. Lymphoid Recovery

    To assess the pace of lymphoid recovery in this patient population.

    Measured: 6 months

  3. Incidence of Grades III-IV GVHD

    To determine the incidence and severity of GVHD in these patients using a combination of cyclophosphamide, tacrolimus and mycophenolate mofetil (MMF) as GVHD prophylaxis.'

    Severity was graded using CTCAE 3.0 (1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death)

    Measured: 6 months

Timeline

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

  1. First posted31 Jan 2007 (estimated)
  2. Study startJan 2006
  3. Primary completionAug 2009
  4. Study completionJun 2010

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
27 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00429143
Sponsor's protocol ID
06U.20
Other IDs
2005-84, JT 1157
Status last verified
May 2025
First submitted
29 Jan 2007
Last updated
4 May 2025
Data monitoring committee
Yes

Publications

  • Grosso D, Carabasi M, Filicko-O'Hara J, Kasner M, Wagner JL, Colombe B, Cornett Farley P, O'Hara W, Flomenberg P, Werner-Wasik M, Brunner J, Mookerjee B, Hyslop T, Weiss M, Flomenberg N. A 2-step approach to myeloablative haploidentical stem cell transplantation: a phase 1/2 trial performed with optimized T-cell dosing. Blood. 2011 Oct 27;118(17):4732-9. doi: 10.1182/blood-2011-07-365338. Epub 2011 Aug 25.

    PubMed 21868572

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Total Body Irradiation (TBI), Donor Lymphocyte Infusion (DLI) and Cyclophosphamide (CY) in people with Hematologic Malignancies, 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 11 inclusion and 7 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 4 May 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 31 May 2013). 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?

Overall Survival of Participants (time frame: 6 months). The study lists 2 primary outcomes in all. 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 NCT00429143, which also lists 1 linked publication.

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 4 May 2025.

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