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Acute Myeloid LeukemiaPhase 2NCT02424968

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

A Phase 2 study testing Anti-Thymocyte Globulin, Cyclosporine and Mycophenolate Mofetil in people with Acute Myeloid Leukemia and B-Cell Non-Hodgkin Lymphoma, run by Robert Lowsky at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 80 yearsHealthy volunteers can take part
What is being tested?
Anti-Thymocyte Globulin, Cyclosporine and Mycophenolate Mofetil
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteUnited States
Study dates
Jun 2015to Apr 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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:
  • Patients must be beyond day 30 and before day 60 after transplant
  • Patients must have evidence of mixed CD3 T-cell chimerism based on the day +28 (+/- 7 days) blood sample showing >= 5% and =< 95% donor type cells
  • Patients must have no evidence of active graft-versus-host disease at the time of the CD8+ memory T-cell infusion; patients with a history of acute GVHD overall grade II based on skin only involvement or upper gastrointestinal (GI) tract involvement only will be eligible; patients with a history of liver or lower GI tract GVHD will not be eligible
  • Patients must be on single immune suppression therapy with either tacrolimus or cyclosporine at the time of CD8+ memory T-cell infusion; prednisone at a physiologic dose of 5 mg per day or less is allowed
  • Patients must have a Karnofsky performance status of >= 60% at the time of the CD8+ memory T-cell infusion
  • Patients must not have an uncontrolled bacterial, fungal or viral infection, defined as progressive symptoms despite therapy, at the time of the CD8+ memory T-cell infusion; asymptomatic viremia is allowed
  • Patients must have adequate organ function and performance status at the time of the CD8+ memory T-cell infusion, defined by the following:
  • Total bilirubin =< 4 mg/dL
  • SGOT or SGPT =< 4 x ULN
  • Creatinine =< 3 mg/dL or estimated creatinine clearance >= 40ml/min

Who cannot join

  • 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
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  • 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
  • Karnofsky performance status (KPS) < 60%
  • Note: Patients positive for hepatitis B and C will be evaluated on a case by case basis

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Stanford University, School of Medicine

    Stanford, California, 94305

Other trials in United States

About this study

Official title: Post Transplant Infusion of Allogeneic CD8 Memory T-Cells as Consolidative Therapy After Non-myeloablative Allogeneic Hematopoietic Cell Transplantation in Patients With Leukemia and Lymphoma

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).

Read the detailed description

Participants undergo total lymphoid irradiation (TLI) on Days -11 to -7 and Days -4 to -1 and receive anti-thymocyte globulin (ATG) per standard institutional practice on Days -11 to -7. Patients also receive oral cyclosporine daily starting on Day -3, and will continue for at least 6 months post-transplant. Patients undergo standard non-myeloablative allogeneic HSCT on Day 0. Patients also receive oral mycophenolate mofetil daily beginning on Day 0 and continuing until Day 28. Participants receive an intravenous infusion of allogeneic cluster of differentiation 8 (CD8)+ memory T-cells over 10 to 20 minutes sometime between day 30 and day 60.

PRIMARY OBJECTIVES:

  1. To determine the rate of conversion to full-donor chimerism (FDC) following a post-transplant infusion (Day 30-60) of freshly-enriched allogeneic CD8+ memory T-cells in patients with acute myeloid leukemia (AML), non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), or Hodgkin lymphoma (HL), who received standard non-myeloablative total lymphoid irradiation (TLI) anti-thymocyte globulin (ATG) transplant conditioning.

SECONDARY OBJECTIVES:

  1. To determine the risk of disease progression, overall and event free survival, and non-relapse mortality.

II. To determine the incidence of acute and chronic graft-versus-host disease (GVHD) following the infusion of allogeneic CD8+ memory T-cells.

OUTLINE:

Patients undergo TLI on days -11 to -7 and -4 to -1 and receive ATG per standard institutional practice on days -11 to -7. Patients also receive cyclosporine orally (PO) daily starting on day -3 and will continue for at least 6 months post-transplant. Patients undergo non-myeloablative allogeneic hematopoietic stem cell transplant (HSCT) on day 0. Patients also receive mycophenolate mofetil PO daily beginning on day 0 and continue until day 28. Based on the patient's status after the initial transplant, patients receive CD8+ memory T-cells intravenously (IV) over 10-20 minutes sometime between day 30 and day 60.

After completion of study treatment, patients are followed up periodically.

Being tested
Anti-Thymocyte Globulin, Cyclosporine, Mycophenolate Mofetil, Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplant, Allogeneic Cluster of Differentiation 8 (CD8)+ Memory T-cells
Keywords
Healthy Stem Cell Donor
Medical subject headings
Leukemia, Myeloid, Acute, Lymphoma, B-Cell, Leukemia, Lymphocytic, Chronic, B-Cell, Hodgkin Disease, Myelodysplastic Syndromes, Myeloproliferative Disorders, Lymphoma, T-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Anti-Thymocyte GlobulinBiological

    Also called Antithymocyte Globulin, Antithymocyte Serum, ATG, ATGAM

    Given per standard institutional practice

  • CyclosporineDrug

    Also called 27-400, Ciclosporin, CsA, Cyclosporin

    Given PO

  • Mycophenolate MofetilDrug

    Also called Cellcept, MMF

    Given PO

  • Nonmyeloablative Allogeneic Hematopoietic Stem Cell TransplantProcedure or surgery

    Also called Non-myeloablative allogeneic transplant, Nonmyeloablative Stem Cell Transplant, NST, Peripheral Blood Stem Cell (PBSC) Transplant

    Undergo nonmyeloablative allogeneic HSCT

  • Allogeneic Cluster of Differentiation 8 (CD8)+ Memory T-cellsBiological

    Also called Allogeneic Lymphocytes, Tumor-Derived Lymphocyte

    Receive CD8+ memory T-cells via IV

  • Total Nodal IrradiationRadiation

    Undergo TLI

Study groups in NCT02424968
Study groupRoleWhat they receive
Infusion of Allogeneic CD8+ Memory T-cellsExperimentalAll participants receive allogeneic CD8+ memory T-cells 30 to 60 days after standard non-myeloablative allogeneic hematopoietic cell transplant (aHCT).
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 3 months

Secondary outcomes (7)

  1. Event-free Survival (EFS

    Event-free survival (EFS) is defined as the number of transplant recipients of allogeneic cluster of differentiation 8 (CD8+) memory T-cells that remain alive at 12 months after transplant without disease relapse. Relapse is defined as bone marrow blasts > 5% . The outcome is expressed as the number of allogeneic CD8+ memory T-cell recipients remaining alive at 1 year after transplant without disease relapse, a number without dispersion.

    Measured: 1 year

  2. Incidence of Acute Graft vs Host Disease (GvHD)

    Occurrence of acute graft vs host disease (aGvHD) following the infusion of allogeneic transplantation of cluster of differentiation 8 (CD8+) memory T-cells will be assessed. The outcome is reported as the number of allogeneic CD8+ memory T-cell recipients who experience aGvHD within 30 days of the cellular infusion, a number without dispersion.

    Measured: Up to 30 days post-infusion

  3. LOWSKY Grade 3 or Higher Toxicities

    Related adverse events, ie, toxicities, ≥ Grade 3 are significant considerations in the treatment of study participants receiving allogeneic transplantation of cluster of differentiation 8 (CD8+) memory T-cells. The outcome is reported as the number of allogeneic CD8+ memory T-cells transplant recipients who experienced ≥ Grade 3 toxicity within 60 days of infusion of the allogeneic transplantation of cluster of differentiation 8 (CD8+) memory T-cells, a number without dispersion.

    Measured: Up to 60 days post-infusion

  4. Chronic Graft vs Host Disease (GvHD)

    The incidence of chronic graft vs host disease (cGvHD) following the infusion of allogeneic transplantation of cluster of differentiation 8 (CD8+) memory T-cells will be assessed. The outcome is reported as the number of allogeneic CD8+ memory T-cell recipients who experience cGvHD more 30 days but within 1 year of the cellular infusion, a number without dispersion.

    Measured: 1 year

  5. Non-relapse Mortality (NRM)

    Non-relapse mortality (NRM) is defined as death without known disease relapse or recurrence. The outcome is expressed as the number of allogeneic CD8+ memory T-cells tr. ansplant recipients whose cause of death was not disease relapse or recurrence, a number without dispersion

    Measured: 1 year

  6. Overall Survival (OS)

    Overall survival (OS) is defined as remaining alive 12 months after the infusion of allogeneic cluster of differentiation 8 (CD8+) memory T-cells. The outcome is reported as the number of allogeneic CD8+ memory T-cell transplant recipients remaining alive at 12 months after the cellular infusion, a number without dispersion

    Measured: 1 year

  7. Disease Progression (TDP)

    Whether or not the treated disease returns, known as disease progression or relapse, is a measure of treatment efficacy. Recipients of allogeneic transplantation of cluster of differentiation 8 (CD8+) memory T-cells were monitored for disease progression through 1 year after the cellular infusion. The outcome is reported as the number of allogeneic CD8+ memory T-cells recipients that experienced disease progression within 12 months (1 year).

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Apr 2015 (estimated)
  2. Study startJun 2015
  3. Primary completion3 Jul 2020
  4. Study completionApr 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02424968
Sponsor's protocol ID
IRB-33058
Other IDs
NCI-2015-00567, 351, BMT288, P01CA049605
Status last verified
May 2021
First submitted
16 Apr 2015
Last updated
24 Jun 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Anti-Thymocyte Globulin, Cyclosporine and Mycophenolate Mofetil in people with Acute Myeloid Leukemia and B-Cell Non-Hodgkin Lymphoma, run by Robert Lowsky at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Full-dose Donor Chimerism (FDC) (time frame: 3 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02424968.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jun 2021.

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Clinical Trial NCT02424968 | AzTrials