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

Primary Purpose

Hematologic Malignancies

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Total Body Irradiation (TBI)

Donor Lymphocyte Infusion (DLI)

Cyclophosphamide (CY)

Tacrolimus

Mycophenolate Mofetil (MMF)

Hematopoietic Stem Cell Transplant (HSCT)

About this trial

This is an interventional treatment trial for Hematologic Malignancies focused on measuring Hematologic Malignancies, Two Step Approach, Haploidentical Transplant

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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
- 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

Exclusion Criteria:

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.

Sites / Locations

Thomas Jefferson University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Haploidentical Allogeneic Transplantation

Arm Description

Patients undergoing hematopoietic stem cell transplant from a partially matched related donor

Outcomes

Primary Outcome Measures

Overall Survival of Participants

To determine overall survival at 6 months post-transplant.

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.

Secondary Outcome Measures

Engraftment Rates

To assess hematopoietic engraftment rates.

Lymphoid Recovery

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

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)

Full Information

NCT ID

NCT00429143

First Posted

January 29, 2007

Last Updated

October 19, 2016

Sponsor

Sidney Kimmel Cancer Center at Thomas Jefferson University

1. Study Identification

Unique Protocol Identification Number

NCT00429143

Brief Title

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

Official Title

A Two Step Approach To Allogeneic Hematopoietic Stem Cell Transplantation for Hematologic Malignancies From HLA Partially-Matched Related Donors

Study Type

Interventional

2. Study Status

Record Verification Date

October 2016

Overall Recruitment Status

Completed

Study Start Date

January 2006 (undefined)

Primary Completion Date

August 2009 (Actual)

Study Completion Date

June 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Sidney Kimmel Cancer Center at Thomas Jefferson University

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hematologic Malignancies

Keywords

Hematologic Malignancies, Two Step Approach, Haploidentical Transplant

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

27 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Haploidentical Allogeneic Transplantation

Arm Type

Experimental

Arm Description

Patients undergoing hematopoietic stem cell transplant from a partially matched related donor

Intervention Type

Radiation

Intervention Name(s)

Total Body Irradiation (TBI)

Other Intervention Name(s)

TBI, radiotherapy

Intervention Description

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

Intervention Type

Biological

Intervention Name(s)

Donor Lymphocyte Infusion (DLI)

Other Intervention Name(s)

DLI, T cell infusion

Intervention Description

DLI given 6 days prior to transplant (HSCT).

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide (CY)

Other Intervention Name(s)

CY, Endoxan, Cytoxan, Neosar, Procytox, Revimmune, cytophosphane

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Tacrolimus

Other Intervention Name(s)

FK-506, fujimycin, Prograf, Advagraf, Protopic

Intervention Description

Tacrolimus given one day prior to transplant (HSCT).

Intervention Type

Drug

Intervention Name(s)

Mycophenolate Mofetil (MMF)

Other Intervention Name(s)

MMF, CellCept, Myfortic

Intervention Description

MMF given one day prior to transplant (HSCT).

Intervention Type

Biological

Intervention Name(s)

Hematopoietic Stem Cell Transplant (HSCT)

Other Intervention Name(s)

HSCT, stem cell transplant

Intervention Description

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

Primary Outcome Measure Information:

Title

Overall Survival of Participants

Description

To determine overall survival at 6 months post-transplant.

Time Frame

6 months

Title

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

Description

Time Frame

6 months

Secondary Outcome Measure Information:

Title

Engraftment Rates

Description

To assess hematopoietic engraftment rates.

Time Frame

6 months

Title

Lymphoid Recovery

Description

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

Time Frame

6 months

Title

Incidence of Grades III-IV GVHD

Description

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 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 Exclusion Criteria: 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Neal Flomenberg, MD

Organizational Affiliation

Thomas Jefferson University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Thomas Jefferson University

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19107

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

21868572

Citation

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.

Results Reference

derived

Links:

URL

http://www.JeffersonHospital.org

Description

Thomas Jefferson University Hospitals

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

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