Donor Peripheral Stem Cell Transplant in Treating Patients With Hematolymphoid Malignancies

Sponsor

Robert Lowsky (Other)

Overall Status

Completed

CT.gov ID

NCT01523223

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
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	Biological: therapeutic allogeneic lymphocytes	Phase 1

Detailed Description

PRIMARY OBJECTIVES:

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:

To determine disease response, time to disease progression, event-free survival, and overall survival following treatment with allogeneic CD8+ memory T-cells.
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.

Study Design

Study Type:

Interventional

Actual Enrollment :

16 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Study Start Date :

Jan 1, 2012

Actual Primary Completion Date :

Sep 1, 2016

Actual Study Completion Date :

Oct 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (DLI) Patients undergo CD8+ memory T-cell infusion over 10-20 minutes.	Biological: therapeutic allogeneic lymphocytes Undergo CD8 memory T-cell infusion Other Names: ALLOLYMPH

Arm

Intervention/Treatment

Experimental: Treatment (DLI)

Patients undergo CD8+ memory T-cell infusion over 10-20 minutes.

Biological: therapeutic allogeneic lymphocytes

Undergo CD8 memory T-cell infusion

Other Names:

ALLOLYMPH

Outcome Measures

Primary Outcome Measures

Occurrence (individual listings and summary) of dose-limiting toxicities [60 days following CD8+ memory T-cell infusion]
Incidence of GVHD [Change from Baseline to 60 days following the CD8+ memory T-cell infusion]

Secondary Outcome Measures

Disease response as assessed by complete remission, partial remission, stable disease, and progressive disease from radiographic and cellular or tissue samples [Change from baseline to 180 days following infusion]
Measured 90 and 180 days following infusion
Incidence of donor-specific chimerism assessed by STR analysis [Change from baseline to 6 months]
Measured monthly for 6 months

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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