CD8+ Memory T-Cells as Consolidative Therapy After Donor Non-myeloablative Hematopoietic Cell Transplant in Treating Patients With Leukemia or Lymphoma

NCT02424968 | Completed Phase 2 Results DMC FDA Drug

• 5 other identifiers: IRB-33058NCI-2015-00567351BMT288P01CA049605
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This phase 2 trial studies how well cluster of differentiation 8 (CD8)+ memory T-cells work as a consolidative therapy following a donor non-myeloablative hematopoietic cell transplant in treating patients with leukemia or lymphoma. Giving total lymphoid irradiation and anti-thymocyte globulin before a donor hematopoietic cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft-versus-host disease). Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening. Once the donated stem cells begin working, the patient's immune system may see the remaining cancer cells as not belonging in the patient's body and destroy them. Giving an infusion of the donor's white blood cells, such as CD8+ memory T-cells, may boost this effect and may be an effective treatment to kill any cancer cells that may be left in the body (consolidative therapy).

Conditions

Acute Myeloid Leukemia; B-Cell Non-Hodgkin Lymphoma; Chronic Lymphocytic Leukemia; Hodgkin Lymphoma; Myelodysplastic Syndrome; Myeloproliferative Neoplasm; T-Cell Non-Hodgkin Lymphoma

Keywords

Healthy Stem Cell Donor

Outcome Measures

Primary Outcomes (1)

• Full-dose Donor Chimerism (FDC)

  A measure of success for the therapeutic infusion of allogeneic transplantation of cluster of differentiation 8 (CD8+) memory T-cells is full-dose donor chimerism (FDC). This means to achieve ≥ 95% donor cells in either the CD3+ blood cell lineage or whole blood, within 90 days of the allogeneic CD8+ memory T-cell infusion. The outcome is reported as the number of participants that achieve FDC within 90 days, a number without dispersion.

  3 months

Secondary Outcomes (7)

• Event-free Survival (EFS

  1 year

• Incidence of Acute Graft vs Host Disease (GvHD)

  Up to 30 days post-infusion

• LOWSKY Grade 3 or Higher Toxicities

  Up to 60 days post-infusion

• Chronic Graft vs Host Disease (GvHD)

  1 year

• Non-relapse Mortality (NRM)

  1 year

Study Arms (1)

Infusion of Allogeneic CD8+ Memory T-cells

EXPERIMENTAL

All participants receive allogeneic CD8+ memory T-cells 30 to 60 days after standard non-myeloablative allogeneic hematopoietic cell transplant (aHCT).

Biological: Anti-Thymocyte Globulin; Drug: Cyclosporine; Drug: Mycophenolate Mofetil; Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplant; Biological: Allogeneic Cluster of Differentiation 8 (CD8)+ Memory T-cells; Radiation: Total Nodal Irradiation

Interventions

Anti-Thymocyte Globulin BIOLOGICAL

Given per standard institutional practice

Also known as: Antithymocyte Globulin, Antithymocyte Serum, ATG, ATGAM, ATS, Thymoglobulin

Infusion of Allogeneic CD8+ Memory T-cells

Cyclosporine DRUG

Given PO

Also known as: 27-400, Ciclosporin, CsA, Cyclosporin, Cyclosporin A, Neoral, OL 27-400, Sandimmun, Sandimmune, SangCya

Infusion of Allogeneic CD8+ Memory T-cells

Mycophenolate Mofetil DRUG

Given PO

Also known as: Cellcept, MMF

Infusion of Allogeneic CD8+ Memory T-cells

Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplant PROCEDURE

Undergo nonmyeloablative allogeneic HSCT

Also known as: Non-myeloablative allogeneic transplant, Nonmyeloablative Stem Cell Transplant, NST, Peripheral Blood Stem Cell (PBSC) Transplant, Peripheral Stem Cell Support, Peripheral Stem Cell Transplant

Infusion of Allogeneic CD8+ Memory T-cells

Allogeneic Cluster of Differentiation 8 (CD8)+ Memory T-cells BIOLOGICAL

Receive CD8+ memory T-cells via IV

Also known as: Allogeneic Lymphocytes, Tumor-Derived Lymphocyte

Infusion of Allogeneic CD8+ Memory T-cells

Total Nodal Irradiation RADIATION

Undergo TLI

Infusion of Allogeneic CD8+ Memory T-cells

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must have a human leukocyte antigen (HLA)-matched or single allele-mismatched adult sibling serving as donor
• Must have a myeloid or lymphoid malignant disease that is treated with TLI and ATG reduced intensity conditioning for allogeneic transplant (any of the following AML, myelodysplastic syndrome \[MDS\], myeloproliferative disease \[MPD\], CLL, B or T-cell NHL, HL)
• Patients who due to age, pre-existing medical conditions, or, prior therapy are considered to be at high risk for regimen related toxicity associated with fully ablative transplant conditioning, and therefore reduced intensity conditioning is recommended
• Ability to understand and the willingness to sign a written informed consent document; patients must have signed informed consent to participate in the trial
• DONOR: Must be an HLA-matched or single allele mismatched sibling of enrolled transplant patient
• DONOR: Must be 18-75 years of age, inclusive
• DONOR: Must be in a state of general good health and have completed a donor evaluation with history, medical examination and standard blood tests within 35 days of starting the hematopoietic cell collection procedure; in order to fairly represent the interests of the donor, the donor evaluation and consent will be performed by a study team member other than the recipient's attending physician
• DONOR: Must have a white blood cell count \> 3.5 x 10\^9/liter, platelets \> 150 x 10\^9/liter and hematocrit \> 35%
• DONOR: Must be capable of undergoing leukapheresis
• DONOR: Must be able to understand and sign informed consent
• DONOR: Must not be seropositive for HIV 1 and 2, hepatitis B surface antigen, hepatitis C antibody, human T-lymphotropic virus (HTLV) antibody, cytomegalovirus (CMV) immunoglobulin M (IgM), or rapid plasma reagin (RPR) (Treponema); donors with prior evidence of hepatitis B core antibody positivity will have a polymerase chain reaction (PCR) test done to evaluate for hepatitis B infection; donors with a positive hepatitis B PCR test are excluded
• DONOR: Females must not be pregnant or lactating
• DONOR: Must not have psychological traits or psychological or medical conditions which make them unlikely to tolerate the procedure
• DONOR: Must not have developed a new malignancy requiring chemotherapy or radiation in the interval since apheresis for initial hematocrit (HCT)
• PATIENT CRITERIA FOR PROCEEDING WITH CD8+ MEMORY T-CELL INFUSION:

You may not qualify if:

• Uncontrolled bacterial, viral or fungal infection defined as currently taking medication and progression of clinical symptoms
• Progressive hemato-lymphoid malignancy despite conventional therapy
• Acute leukemia not in remission
• Chronic myelogenous leukemia (CML)
• Active central nervous system (CNS) involvement of the underlying malignancy
• Human immunodeficiency virus (HIV) positive
• Pregnant or lactating
• Prior malignancy (EXCEPTION: diagnosed \> 5 years ago without evidence of disease, OR treated =\< 5 years ago but have a greater than 50% chance of life expectancy of \>= 5 years for that malignancy)
• Have a psychiatric disorder(s) or psychosocial circumstance(s) which in the opinion of the primary physician would place the patient at an unacceptable risk from transplant
• Ejection fraction \< 30%, or uncontrolled cardiac failure
• Diffusing capacity of the lung for carbon monoxide (DLCO) \< 40% predicted
• Total bilirubin \> 3 mg/dL
• Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) \> 4 x upper limit of normal (ULN)
• Creatinine \> 2 mg/dL and an estimated creatinine clearance =\< 40 mL/min
• Poorly controlled hypertension despite multiple antihypertensive medication OR

Sponsors & Collaborators

• Robert Lowsky: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Stanford University, School of Medicine

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Lymphoma, B-Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Hodgkin Disease; Myelodysplastic Syndromes; Myeloproliferative Disorders; Lymphoma, T-Cell

Interventions

Antilymphocyte Serum; thymoglobulin; Cyclosporine; Cyclosporins; Mycophenolic Acid; Transplantation; Peripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Surgical Procedures, Operative; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics

Results Point of Contact

• Title: Robert Lowsky, Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy)
• Organization: Stanford University

rlowsky@stanford.edu

650-723-0822

Study Officials

• Robert Lowsky

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: April 16, 2015
• First Posted: April 23, 2015
• Study Start: June 1, 2015
• Primary Completion: July 3, 2020
• Study Completion: April 1, 2021
• Last Updated: June 24, 2021
• Results First Posted: June 24, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)