Have you or your loved ones been diagnosed with recurrent childhood acute lymphoblastic leukemia?

You may be eligible to participate in a recurrent childhood acute lymphoblastic leukemia clinical trial.

Have you or your loved ones been diagnosed with recurrent childhood acute lymphoblastic leukemia? You may be eligible to participate in a recurrent childhood acute lymphoblastic leukemia clinical trial.

What is a clinical trial? Is participating in a clinical trial right for you? Learn more

Recurrent Childhood Acute Lymphoblastic Leukemia Clinical Trial in Seattle WA

NCT03326921 | Phase 1 | Interventional

Have you or your loved ones been diagnosed with recurrent childhood acute lymphoblastic leukemia?

You may be eligible to participate in a recurrent childhood acute lymphoblastic leukemia clinical trial.

Suspended

Male & Female

Up to 75

Years old

This study is looking to recruit 24 Participants

This phase I trial studies the side effects and best dose of CD4+ and CD8+ HA-1 T cell receptor (TCR) (HA-1 T TCR) T cells in treating patients with acute leukemia that persists, has come back (recurrent) or does not respond to treatment (refractory) following donor stem cell transplant. T cell receptor is a special protein on T cells that helps them recognize proteins on other cells including leukemia. HA-1 is a protein that is present on the surface of some peoples' blood cells, including leukemia. HA-1 T cell immunotherapy enables genes to be added to the donor cells to make them recognize HA-1 markers on leukemia cells.

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Details for the study

Brief Title

HA-1 T TCR T Cell Immunotherapy for the Treatment of Patients With Relapsed or Refractory Acute Leukemia After Donor Stem Cell Transplant

Official Title

Phase I Study of Adoptive Immunotherapy With CD8+ and CD4+ Memory T Cells Transduced to Express an HA-1-Specific T Cell Receptor (TCR) for Children and Adults With Recurrent Acute Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation (HCT)

Brief Summary

This phase I trial studies the side effects and best dose of CD4+ and CD8+ HA-1 T cell receptor (TCR) (HA-1 T TCR) T cells in treating patients with acute leukemia that persists, has come back (recurrent) or does not respond to treatment (refractory) following donor stem cell transplant. T cell receptor is a special protein on T cells that helps them recognize proteins on other cells including leukemia. HA-1 is a protein that is present on the surface of some peoples' blood cells, including leukemia. HA-1 T cell immunotherapy enables genes to be added to the donor cells to make them recognize HA-1 markers on leukemia cells.

Detailed Description

OUTLINE:

This is a dose-escalation study of CD4+ and CD8+ HA-1 TCR T cells.

Patients receive fludarabine for 1-3 doses 3-14 days prior to HA-1 TCR T cell administration.
Patients then receive CD4+ and CD8+ HA-1 TCR T cells intravenously (IV) over 1 hour.

After completion of study treatment, patients are followed up closely for 12 weeks and then
every 6 months for years 1-5, and every year for years 6-15.

Treatments and/or Procedures

CD8+ and CD4+ Donor Memory T cells expressing HA1 Specific TCR

Given IV

Fludarabine

Given IV

Laboratory biomarker analysis

Correlative studies

Outcome Measures

Outcome measures are the tests that investigators perform to prove whether or not a treatment being tested in a clinical trial is having any effect.

Primary

Feasibility of manufacturing minor H antigen (HA-1) T cell receptor (TCR) CD8+ and CD4+ T cells

Proportion of participants for whom a HA-1 TCR T cell product can be produced.

At time of T cell infusion (at day 0)

Primary

Feasibility of administering minor H antigen (HA-1) T cell receptor (TCR) CD8+ and CD4+ T cells

Proportion of participants for whom a HA-1 TCR T cell product can be administered.

At time of T cell infusion (at day 0)

Primary

Incidence of dose-limiting toxicities of HA-1 T cell receptor (TCR) T cells

Toxicities will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.

Up to 12 weeks after T-cell infusion

Secondary

Specific cytolytic activity of HA-1 T cell receptor (TCR) CD8+ and CD4+ T cells against HLA-A*0201+ HA-1+ target cells after adoptive T cell transfer

By in vitro chromium release assay or flow cytometric degranulation assay (CD107a) using samples of peripheral blood and/or bone marrow collected from patients after adoptive T cell transfer.

Up to 1 year

Secondary

Duration of in vivo persistence of transferred HA-1 T cell receptor (TCR) CD4+ T cells in peripheral blood

Evaluated by tetramer and/or molecular tracking e.g. quantitative polymerase chain reaction (qPCR).

Up to 1 year

Secondary

Duration of in vivo persistence of transferred HA-1 T cell receptor (TCR) CD8+ T cells in peripheral blood

Evaluated by tetramer and/or molecular tracking e.g. qPCR.

Up to 1 year

Secondary

Presence, proportion and persistence of HA-1 T cell receptor (TCR) CD4+ T cells in the bone marrow

Evaluated by tetramer and/or molecular tracking e.g. qPCR.

Up to 1 year

Secondary

Presence, proportion and persistence of HA-1 T cell receptor (TCR) CD8+ T cells in the bone marrow

Evaluated by tetramer and/or molecular tracking e.g. qPCR.

Up to 1 year

Secondary

Specific cytolytic activity of HA-1 T cell receptor (TCR) CD8+ and CD4+ T cells against HLA-A*0201+ HA-1+ target cells before adoptive T cell transfer

Assessed by in vitro chromium release assay or equivalent cytotoxicity assay.

At the time of T cell infusion (at day 0)

Secondary

Reduction of leukemia in the bone marrow in patients who have measurable leukemia in the marrow prior to HA-1 T cell receptor (TCR) T cell infusion

Quantified by flow cytometry to determine percentage of leukemic cells in the marrow.

Up to 1 year

Secondary

Reduction of recipient normal hematopoietic cells in the bone marrow in patients who have measurable recipient normal hematopoietic cells in the marrow prior to HA-1 T cell receptor (TCR) T cell infusion

Quantified by variable number tandem repeat (VNTR) to determine percentage of normal recipient and donor cells in the marrow.

Up to 1 year

Secondary

Proportion of patients who develop new or recurrent symptoms or signs of graft-versus-host disease

Assessed using clinical evaluation and standard clinical graft versus host disease (GVHD) grading criteria

Up to 1 year

Study Criteria

Inclusion Criteria:

  -  Patient age 0-75 years at the time of enrollment.

  -  Patients must express HLA-A*0201

  -  Patients must have the HA-1(H) genotype (RS_1801284: A/G, A/A)

  -  Patients must have an adult donor for HCT who is adequately HLA matched by
     institutional standards (includes HLA-matched related or unrelated donors, and
     HLA-mismatched family donors, including haploidentical donors) and is either:

       -  HLA-A*0201 positive and HA-1(H) negative (RS_1801284: G/G) or

       -  HLA-A*0201 negative

  -  Patients who are currently undergoing or who previously underwent allogeneic HCT for

       -  Acute myeloid leukemia (AML) of any subtype

       -  Acute lymphoid leukemia (ALL) of any subtype

       -  Mixed phenotype/undifferentiated/any other type of acute leukemia, including
          blastic plasmacytoid dendritic cell neoplasm

       -  Chronic myeloid leukemia with a history of blast crisis and:

            -  With relapse or refractory disease (>= 5% marrow blasts, or circulating
               blasts) at any time after HCT

            -  With persistent rising minimal residual disease (defined as detectable
               disease by morphology, flow cytometry, molecular or cytogenetic testing but
               < 5% marrow blasts by morphology, no circulating blasts on >= 2 of two
               consecutive tests), refractory or ineligible for treatment with tyrosine
               kinase inhibitors at any time after HCT

       -  Myelodysplastic syndrome (MDS) of any subtype

       -  Chronic myelomonocytic leukemia (CMML)

       -  Juvenile myelomonocytic leukemia (JMML)

  -  Patients must be able to understand and be willing to give informed consent;
     decision-impaired adults may consent with their legally authorized representative;
     parent or legal representative will be asked to consent for patients younger than 18
     years old

  -  Patients must agree to participate in long-term follow-up for up to 15 years if they
     are enrolled in the study and receive T cell infusion

  -  Patients who have relapsed or have MRD after HCT may receive other agents for
     treatment of disease and remain eligible for the protocol

  -  A specific performance status score is not required for enrolling on the protocol; a
     delay in infusion of the HA-1 TCR T cells may be required for patients with low
     performance status

DONOR SELECTION INCLUSION

  -  Donor age >= 18 years

  -  Donors must be able to give informed consent

  -  Patients must have an adult donor for HCT who is adequately HLA matched by
     institutional standards (includes HLA-matched related or unrelated donors, and
     HLA-mismatched family donors, including haploidentical donors) and is either:

       -  HLA-A*0201 positive and HA-1(H) negative (RS_1801284: G/G) or

       -  HLA-A*0201 negative

Exclusion Criteria:

  -  Medical or psychological conditions that would make the patient unsuitable candidate
     for cell therapy at the discretion of the principal investigator (PI)

  -  Fertile patients unwilling to use contraception during and for 12 months after
     treatment

  -  Patients with a life expectancy < 3 months of enrollment from coexisting disease other
     than leukemia

  -  Patients who develop grade IV acute GVHD or severe chronic GVHD following most recent
     transplant prior to enrollment on the protocol

  -  The presence of organ toxicities will not necessarily exclude patients from enrolling
     on the protocol at the discretion of the PI; however, a delay in the infusion of HA-1
     TCR T cells may be required

DONOR SELECTION EXCLUSION

  -  Donors who are HIV-1, HIV-2, human T-lymphotropic virus (HTLV)-1, HTLV-2 seropositive
     or with active hepatitis B or hepatitis C virus infection

  -  Unrelated donor residing outside of the United States of America (USA) unless the
     donor screening, testing and leukapheresis occur at an NMDP-affiliated and qualified
     donor center and are facilitated by the NMDP.