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Donor Peripheral Stem Cell Transplant in Treating Patients With Hematolymphoid Malignancies

Primary Purpose

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)

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
therapeutic allogeneic lymphocytes
Sponsored by
Robert Lowsky
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Stanford University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (DLI)

Arm Description

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

Outcomes

Primary Outcome Measures

Occurrence (individual listings and summary) of dose-limiting toxicities
Incidence of GVHD

Secondary Outcome Measures

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

Full Information

First Posted
January 27, 2012
Last Updated
March 16, 2019
Sponsor
Robert Lowsky
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT01523223
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2016
Overall Recruitment Status
Completed
Study Start Date
January 2012 (undefined)
Primary Completion Date
September 2016 (Actual)
Study Completion Date
October 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Robert Lowsky
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. 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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (DLI)
Arm Type
Experimental
Arm Description
Patients undergo CD8+ memory T-cell infusion over 10-20 minutes.
Intervention Type
Biological
Intervention Name(s)
therapeutic allogeneic lymphocytes
Other Intervention Name(s)
ALLOLYMPH
Intervention Description
Undergo CD8 memory T-cell infusion
Primary Outcome Measure Information:
Title
Occurrence (individual listings and summary) of dose-limiting toxicities
Time Frame
60 days following CD8+ memory T-cell infusion
Title
Incidence of GVHD
Time Frame
Change from Baseline to 60 days following the CD8+ memory T-cell infusion
Secondary Outcome Measure Information:
Title
Disease response as assessed by complete remission, partial remission, stable disease, and progressive disease from radiographic and cellular or tissue samples
Description
Measured 90 and 180 days following infusion
Time Frame
Change from baseline to 180 days following infusion
Title
Incidence of donor-specific chimerism assessed by STR analysis
Description
Measured monthly for 6 months
Time Frame
Change from baseline to 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Lowsky
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
29572391
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.
Results Reference
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Donor Peripheral Stem Cell Transplant in Treating Patients With Hematolymphoid Malignancies

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