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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified May 2010 by Massachusetts General Hospital.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00981760
First received: September 18, 2009
Last updated: May 3, 2010
Last verified: May 2010
  Purpose

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.


Condition Intervention Phase
Non-Hodgkin's Lymphoma
Hodgkin's Lymphoma
Multiple Myeloma
Radiation: Total Body Irradiation
Drug: Fludarabine
Procedure: Recipient Leukocyte Infusion
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Intentional Rejection of the Donor Graft Using Recipient Leukocyte Infusion(s) Following Nonmyeloablative Allogeneic Stem Cell Transplantation

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • To develop a conditioning regimen achieving initial mixed chimerism of HLA-mismatched related donor CD34+ cells without GVHD [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Evaluate the incidence of acute and chronic GVHD [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Evaluate the incidence of loss of donor grafts [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To evaluate progression-free and overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To evaluate anti-tumor responses following this transplant strategy [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: July 2008
Estimated Study Completion Date: June 2010
Estimated Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1
Conditioning regimen of total body irradiation (TBI) before the stem cell transplant
Radiation: Total Body Irradiation
One low-dose total body irradiation 4-6 hours before the infusion of donor's stem cells.
Other Name: 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
Other Name: RLI
Experimental: Group 2
Receive fludarabine for three days before the TBI
Radiation: Total Body Irradiation
One low-dose total body irradiation 4-6 hours before the infusion of donor's stem cells.
Other Name: TBI
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
Other Name: RLI

Detailed 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.
  Eligibility

Ages Eligible for Study:   18 Years to 74 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00981760

Contacts
Contact: Bimal Dey, MD 617-724-1124
Contact: Amy Karr 617-726-1456

Locations
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02214
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Bimal Dey, MD Massachuestts General Hospital
  More Information

No publications provided

Responsible Party: Bimal Dey, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00981760     History of Changes
Other Study ID Numbers: 07-068
Study First Received: September 18, 2009
Last Updated: May 3, 2010
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
RLI
stem cell transplantation
fludarabine

Additional relevant MeSH terms:
Hodgkin Disease
Lymphoma
Lymphoma, Non-Hodgkin
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Fludarabine
Fludarabine monophosphate
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 28, 2014