Description:
This phase I trial studies the side effects and the best dose of donor CD8+ memory T-cells in
treating patients with hematolymphoid malignancies. Giving low dose of chemotherapy before a
donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may
also stop the patient's immune system from rejecting the donor's stem cells. The donated stem
cells may replace the patient's immune cells and help destroy any remaining cancer cells
(graft-versus-cancer effects). Giving an infusion of the donor's T cells (donor lymphocyte
infusion) after the transplant may help increase this effect
Title
- Brief Title: Donor Peripheral Stem Cell Transplant in Treating Patients With Hematolymphoid Malignancies
- Official Title: A Phase I Study of CD8 Memory T-Cell Donor Lymphocyte Infusion for Relapse of Hematolymphoid Malignancies Following Matched Related Donor Allogeneic Hematopoietic Cell Transplantation
Clinical Trial IDs
- ORG STUDY ID:
BMT243
- SECONDARY ID:
NCI-2012-00044
- SECONDARY ID:
SU-01272012-9028
- SECONDARY ID:
22626
- NCT ID:
NCT01523223
Conditions
- Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
- Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
- Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
- Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
- Adult Nasal Type Extranodal NK/T-cell Lymphoma
- Cutaneous B-cell Non-Hodgkin Lymphoma
- Extranodal Marginal Zone B-cell Lymphoma
- Hepatosplenic T-cell Lymphoma
- Intraocular Lymphoma
- Nodal Marginal Zone B-cell Lymphoma
- Peripheral T-cell Lymphoma
- Recurrent Adult Acute Lymphoblastic Leukemia
- Recurrent Adult Acute Myeloid Leukemia
- Recurrent Adult Burkitt Lymphoma
- Recurrent Adult Diffuse Large Cell Lymphoma
- Recurrent Adult Diffuse Mixed Cell Lymphoma
- Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
- Recurrent Adult Grade III Lymphomatoid Granulomatosis
- Recurrent Adult Hodgkin Lymphoma
- Recurrent Adult Immunoblastic Large Cell Lymphoma
- Recurrent Adult Lymphoblastic Lymphoma
- Recurrent Adult T-cell Leukemia/Lymphoma
- Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
- Recurrent Grade 1 Follicular Lymphoma
- Recurrent Grade 2 Follicular Lymphoma
- Recurrent Grade 3 Follicular Lymphoma
- Recurrent Mantle Cell Lymphoma
- Recurrent Marginal Zone Lymphoma
- Recurrent Mycosis Fungoides/Sezary Syndrome
- Recurrent Small Lymphocytic Lymphoma
- Refractory Chronic Lymphocytic Leukemia
- Relapsing Chronic Myelogenous Leukemia
- Splenic Marginal Zone Lymphoma
- Waldenstrom Macroglobulinemia
Interventions
Drug | Synonyms | Arms |
---|
therapeutic allogeneic lymphocytes | ALLOLYMPH | Treatment (DLI) |
Purpose
This phase I trial studies the side effects and the best dose of donor CD8+ memory T-cells in
treating patients with hematolymphoid malignancies. Giving low dose of chemotherapy before a
donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may
also stop the patient's immune system from rejecting the donor's stem cells. The donated stem
cells may replace the patient's immune cells and help destroy any remaining cancer cells
(graft-versus-cancer effects). Giving an infusion of the donor's T cells (donor lymphocyte
infusion) after the transplant may help increase this effect
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the feasibility of purifying allogeneic CD8+ memory T-cells suitable for
clinical application and to determine the safety and maximum tolerated dose (MTD) of these
cells in patients with recurrent or refractory hematolymphoid malignancies following
allogeneic hematopoietic cell transplant (HCT).
SECONDARY OBJECTIVES:
I. To determine disease response, time to disease progression, event-free survival, and
overall survival following treatment with allogeneic CD8+ memory T-cells.
II. To assess donor specific chimerism before and at designated time points after treatment
with allogeneic CD8+ memory T-cells.
OUTLINE: This is a dose-escalation study.
Patients undergo CD8+ memory T-cell infusion over 10-20 minutes.
Trial Arms
Name | Type | Description | Interventions |
---|
Treatment (DLI) | Experimental | Patients undergo CD8+ memory T-cell infusion over 10-20 minutes. | - therapeutic allogeneic lymphocytes
|
Eligibility Criteria
Inclusion Criteria:
- Patients must have undergone a human leukocyte antigen (HLA) matched (sibling)
allogeneic HCT for a hematologic or lymphoid malignancy other than chronic myelogenous
leukemia (CML) who have recurrent or persistent disease and are otherwise eligible for
donor leukocyte infusions CML patients with persistent disease after receiving donor
lymphocyte infusion of at least 1x10^8cells/kg will be eligible for CD8+ memory T cell
infusion
- Patients must have no evidence of active graft-versus-host disease and must be on a
stable immunosuppressive regimen without a change in drugs dosage in the 4 weeks prior
to the planned CD8+ memory T cell infusion
- Patients must not have any active infections
- Patients must have a performance status of > 70% on the Karnofsky scale
- Serum creatinine of < 2 mg/dl or creatinine clearance of > 50 cc/min
- Bilirubin of < 3 mg/dl Transaminases < 3 times the upper limit of normal
- Patients must have negative antibody serology for the human immunodeficiency virus
(HIV1 and 2) and hepatitis C virus and negative test for hepatitis B surface antigen
DONOR:
- Donors must be an HLA matched sibling
- Donors must be 18-75 years of age, inclusive
- Donors must be in a state of general good health
- Donors must have a white blood cell count > 3.5 x 10^9/liter DONOR: Platelets > 150 x
10^9/liter
- Donors: Hematocrit > 35%
- Donors must be capable of undergoing leukapheresis
- Donors must not be seropositive for HIV 1 and 2, Hepatitis B surface antigen,
Hepatitis B core antibody, Hepatitis C antibody, human T-lymphotropic virus (HTLV)
antibody, cytomegalovirus (CMV) immunoglobulin (Ig)M, or Rapid Plasma Reagin (RPR)
(Treponema)
- Female donors must not be pregnant or lactating
Exclusion Criteria:
- Diagnosis of CML except patients who have failed prior donor leukocyte infusion with a
minimum cell dose of 1x10^8 cells/kg
- Patients who have been diagnosed with a second cancer (except carcinoma in situ of the
cervix and basal cell carcinoma of the skin) which is currently active or has been
treated within three years prior to screening
Maximum Eligible Age: | 75 Years |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Occurrence (individual listings and summary) of dose-limiting toxicities |
Time Frame: | 60 days following CD8+ memory T-cell infusion |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | Disease response as assessed by complete remission, partial remission, stable disease, and progressive disease from radiographic and cellular or tissue samples |
Time Frame: | Change from baseline to 180 days following infusion |
Safety Issue: | |
Description: | Measured 90 and 180 days following infusion |
Measure: | Incidence of donor-specific chimerism assessed by STR analysis |
Time Frame: | Change from baseline to 6 months |
Safety Issue: | |
Description: | Measured monthly for 6 months |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Completed |
Lead Sponsor: | Robert Lowsky |
Last Updated
March 19, 2019