Donor Peripheral Stem Cell Transplant in Treating Patients With Hematolymphoid Malignancies

Phase 1

Completed

• Conditions: Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Waldenstrom Macroglobulinemia; Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Hepatosplenic T-cell Lymphoma
• Interventions: Biological: therapeutic allogeneic lymphocytes

• Registration Number: NCT01523223
• Lead Sponsor: Robert Lowsky

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.

Study Timeline

• Study Start: 2012-01
• Study First Submitted: 2012-01-27
• Study First Submitted QC: 2012-01-31
• Study First Posted: 2012-02-01
• Status Verified: 2016-07
• Primary Completion: 2016-09
• Study Completion: 2016-10
• Last Update Submitted: 2023-11-20
• Last Update Posted: 2023-11-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (DLI)	therapeutic allogeneic lymphocytes	Patients undergo CD8+ memory T-cell infusion over 10-20 minutes.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (1)

Stanford University; 🇺🇸 Stanford, California, United States