Intentional Rejection of the Donor Graft Using Recipient Leukocyte Infusion(s) Following Nonmyeloablative Allogeneic Stem Cell Transplantation

Multiple Myeloma Clinical Trial

Official title:

Intentional Rejection of the Donor Graft Using Recipient Leukocyte Infusion(s) Following Nonmyeloablative Allogeneic Stem Cell Transplantation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00981760
• Other study ID #: 07-068
• Status: Recruiting
• Phase: Phase 2/Phase 3
• First received: September 18, 2009
• Last updated: May 3, 2010
• Start date: July 2008
• Est. completion date: June 2010

Study information

• Verified date: May 2010
• Source: Massachusetts General Hospital
• Contact: Bimal Dey, MD
• Phone: 617-724-1124
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

One risk of a stem cell transplant is that the donated stem cells do not grow in the recipient. This is called graft rejection. Previous laboratory research has suggested that the reaction between the recipient's cells and the donor's cells that causes graft rejection is associated with an anti-cancer effect. In this research study the investigators will give participants some of their own white blood cells after their transplant. This is called a recipient leukocyte infusion (RLI). This is done to cause the participant's immune system to react against the donor's cells and reject the transplant. The purpose of this research study is to learn if the graft rejection has an anti-cancer effect.

Description:

• The first 10 participants (Group 1) will receive a conditioning regimen of total body irradiation (TBI) before the stem cell transplant. It is possible this conditioning regimen may suppress the immune system enough. This can cause the stem cell transplant to be rejected to quickly. It is necessary for the transplant to begin to grow before it is rejected. If the participants in Group 1 reject their stem cell transplant too quickly, the next group of 10 participants (Group 2) will receive a medication called fludarabine for three days before the TBI. The purpose of adding fludarabine is to suppress the immune system enough to allow the transplant to initially grow. An additional RLI may be given 2 weeks after the first RLI.

• Before the conditioning regimen (either TBI or fludarabine), participants will undergo a procedure to collect their white blood cells called leukapheresis. The white blood cells collected will then be frozen and stored and given to the participant as an RLI on Day 38 after their stem cell transplant.

• Participants will receive their donor's stem cells about 4-6 hours after TBI. They will also receive the following medications to prevent GVHD: Cyclosporine orally until about day 35 and Mycophenolate Mofetil (MMF) orally until 21 days after the stem cell transplant.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: June 2010
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 74 Years

Eligibility

Inclusion Criteria:

• Chemorefractory non-Hodgkin's or Hodgkin's lymphoma or multiple myeloma

• Estimated disease-free survival of less than one year

• 18-74 years of age

• ECOG Performance Status of 0,1 or 2

Exclusion Criteria:

• Patients whose life expectancy is limited by diseases other than their malignancy

• Patients who have a 5/6 or better matched related donor or a 4/6 or better umbilical cord blood donor and who are medically eligible for conventional myeloablative or non-myeloablative transplant

• Cardiac disease: symptomatic congestive heart failure or RVG or echocardiogram determined left ventricular ejection fraction of <30%, active angina pectoris, or uncontrolled hypertension

• Pulmonary disease: severe chronic obstructive lung disease, or symptomatic restrictive lung disease, or corrected DLCO of <40% of predicted

• Renal disease: serum creatinine > 3.0mg/dl

• Hepatic disease: serum bilirubin > 3.0mg/dl or alkaline phosphatase, SGOT or SGPT >3x normal

• Neurologic disease: symptomatic leukoencephalopathy, active CNS malignancy or other neuropsychiatric abnormalities believed to preclude transplantation

• Uncontrolled infection

• RLI might involve the infusion of circulating tumor cells to the patients. To minimize the risk, patients who have evidence of circulating tumor cells by light microscopy and flow cytometry will be excluded

• Patients with acute leukemia

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hodgkin Disease
• Hodgkin's Lymphoma
• Lymphoma
• Lymphoma, Non-Hodgkin
• Multiple Myeloma
• Non-Hodgkin's Lymphoma

Intervention

Radiation:
• Total Body Irradiation
One low-dose total body irradiation 4-6 hours before the infusion of donor's stem cells.

Drug:
• Fludarabine
Given intravenously over 30 minutes for three days. Last dose given two days before TBI.

Procedure:
• Recipient Leukocyte Infusion
Infusion of participant's white blood cells given 5 weeks after the stem cell transplant if there is evidence of the stem cell graft having partially taken and no evidence of GVHD

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To develop a conditioning regimen achieving initial mixed chimerism of HLA-mismatched related donor CD34+ cells without GVHD		2 years	No
Primary	To determine the safety including acute GVHD and transplant related mortality at <100 days of this regimen when followed by infusion of RLI to induce deliberate rejection of donor graft		2 years	Yes
Secondary	Evaluate the incidence of acute and chronic GVHD		2 years	No
Secondary	Evaluate the incidence of loss of donor grafts		2 years	No
Secondary	To evaluate progression-free and overall survival		2 years	No
Secondary	To evaluate anti-tumor responses following this transplant strategy		2 years	No