Clinical trial NCT01523223: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
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
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2012-02-01
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase 1 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 to 20 minutes.

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

Primary outcomes:
measure: Occurrence (individual listings and summary) of dose-limiting toxicities
timeFrame: 60 days following CD8+ memory T-cell infusion
measure: Incidence of GVHD
timeFrame: Change from Baseline to 60 days following the CD8+ memory T-cell infusion
Secondary outcomes:
measure: Disease response as assessed by complete remission, partial remission, stable disease, and progressive disease from radiographic and cellular or tissue samples
timeFrame: Change from baseline to 180 days following infusion
measure: Incidence of donor-specific chimerism assessed by STR analysis
timeFrame: Change from baseline to 6 months
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University
state: California
Study officials:
affiliation: Stanford University
name: Robert Lowsky
role: PRINCIPAL_INVESTIGATOR
References:
citation: Muffly L, Sheehan K, Armstrong R, Jensen K, Tate K, Rezvani AR, Miklos D, Arai S, Shizuru J, Johnston L, Meyer E, Weng WK, Laport GG, Negrin RS, Strober S, Lowsky R. Infusion of donor-derived CD8+ memory T cells for relapse following allogeneic hematopoietic cell transplantation. Blood Adv. 2018 Mar 27;2(6):681-690. doi: 10.1182/bloodadvances.2017012104.