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

Hematologic Malignancies Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00429143
• Other study ID #: 06U.20
• Secondary ID: 2005-84
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: January 29, 2007
• Last updated: May 30, 2013
• Start date: January 2006
• Est. completion date: June 2010

Study information

• Verified date: May 2013
• Source: Thomas Jefferson University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: June 2010
• Est. primary completion date: August 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. 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.

2. 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.

3. Patients without a well-matched unrelated donor or those who have a disease status that precludes a wait for an identified unrelated donor.

4. 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

5. Performance status > 60% (Karnofsky)

6. Patients must be willing to use contraception if they have childbearing potential

7. Able to give informed consent

Exclusion Criteria:

1. An eligible HLA-identical sibling donor.

2. Performance status < 60% (Karnosfsky)

3. HIV positive

4. Active involvement of the central nervous system with malignancy

5. Psychiatric disorder that would preclude patients from signing an informed consent

6. Pregnancy

7. Patients with life expectancy of < 6 months for reasons other than their underlying hematologic/oncologic disorder.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hematologic Malignancies
• Neoplasms

Intervention

Radiation:
• Total Body Irradiation (TBI)
TBI twice daily days 6-9 prior to transplant (HSCT)

Biological:
• Donor Lymphocyte Infusion (DLI)
DLI given 6 days prior to transplant (HSCT).

Drug:
• Cyclophosphamide (CY)
Cyclophosphamide given once daily at 60 mg/kg on days 2 and 3 prior to transplant (HSCT).
• Tacrolimus
Tacrolimus given one day prior to transplant (HSCT).
• Mycophenolate Mofetil (MMF)
MMF given one day prior to transplant (HSCT).

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

Locations

Country	Name	City	State
United States	Thomas Jefferson University	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Thomas Jefferson University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival of Participants	To determine overall survival at 6 months post-transplant.	6 months	No
Primary	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.	6 months	Yes
Secondary	Engraftment Rates	To assess hematopoietic engraftment rates.	6 months	Yes
Secondary	Lymphoid Recovery	To assess the pace of lymphoid recovery in this patient population.	6 months	No
Secondary	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)	6 months	Yes

External Links

•   Kimmel Cancer Center at Thomas Jefferson University, an NCI-Designated Cancer Center
•   Thomas Jefferson University Hospitals