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

Stopped early · Phase 1

Conditions studied: Non Hodgkin's Lymphoma, Hodgkin Disease, Multiple Myeloma

In brief

The proposed study is based on our observation of paradoxical tumor regression after rejection of the donor graft in conjunction with the results of our murine experiments. We hypothesize that clinically meaningful responses can be achieved in patients with advanced malignancies with a transplant strategy using nonmyeloablative conditioning and related mismatched donor stem cell transplant where the intention will be to initially achieve mixed chimerism which will be followed by recipient lymphocyte infusion (RLI) in an attempt to deliberately reject the donor graft. This will lead to the development of novel transplant strategies for achieving antitumor effects without the risk of graft versus host disease (GVHD). This proposed protocol is a Pilot Study that will evaluate the safety of this outpatient transplant strategy, i.e., establishment of initial mixed chimerism followed by RLI for donor graft rejection, in patients with advanced lymphomas, and multiple myeloma. In addition, because RLI have been reported to reverse ongoing GVHD, this approach might potentially reverse GVHD while achieving antitumor responses if this complication unexpectedly occurs.

Key facts

Study ID: NCT00909948
Run by: Massachusetts General Hospital
People needed: 7
Starts: 2008-11-01
Expected to finish: 2012-08-01
Last updated by the study team: 2018-03-29

Who can join

Age: 18 and older, up to 75. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Patients with chemorefractory non-Hodgkin's or Hodgkin's lymphoma or multiple myeloma.
Criteria for consideration of enrollment will include:
primary refractory or refractory relapsed disease for which autologous HCT is unlikely to be beneficial;
relapse after autologous HCT
ineligibility for standard myeloablative or nonmyeloablative allo-HCT because of either lack of a donor or patient considerations
Non Hodgkin's lymphoma, or Hodgkin's lymphoma: primary refractory or refractory relapse
Multiple myeloma; primary refractory or refractory relapse
Patients with the above malignancies who have had a previous autologous or allogeneic bone marrow or stem cell transplant.
An estimated disease-free survival of less than one year.
Age 18 to age < 75 years
ECOG performance status of 0, 1, or 2.

You may not qualify if…

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 will be excluded
Cardiac disease: symptomatic congestive heart failure or RVG or echocardiogram determined LVEF ogf< 30%, active angina pectoris or uncontrolled hypertension
Pulmonary disease: severe chronic obstructive lung disease, or symptomatic restrictive lung disease, or corrected DLCO < 40% of predicted
Renal disease: serum creatinine > 3.0 mg/dl.
Hepatic disease: serum bilirubin > 3.0 mg/dl or alkaline phosphatase, SGOT or SGPT > 3 x ULN
Neurologic disease: symptomatic leukoencephalopathy, active CNS malignancy or other neuropsychiatric abnormalities believed to preclude transplantation (pervious CNS malignancy presently in CR is not an exclusion)
Uncontrolled infection.
Recipient leukocyte infusion (RLI) might involve the infusion of circulating tumor cells to the patients. To minimize this risk patients who have evidence of circulating tumor cells by light microscopy and flow cytometry will be excluded
Patients with acute leukemia will be excluded because they will likely have much greater circulating tumor burden, which would increase the risk of infusion of clonal tumor cells

Where it is running

Massachusetts General Hospital — Boston, Massachusetts, United States

Full record on ClinicalTrials.gov

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