Administration of Donor MultiTAA-Specific T Cells for ALL (STELLA)

December 4, 2024 updated by: Bilal Omer, Baylor College of Medicine

Administration of Donor-Derived Multi-Tumor-Associated Antigen (TAA)-Specific T Cells to Patients With ALL

This study uses special blood cells called multiple tumor-associated antigen (TAA)-specific T cells to treat patients with acute lymphoblastic leukemia (ALL) which has come back, or may come back, or has not gone away after standard treatment, including an allogeneic hematopoietic stem cell transplant (HSCT).

The investigators have previously used this sort of therapy to treat Hodgkin or non-Hodgkin lymphomas that are infected with Epstein-Barr virus (EBV). EBV is found in cancer cells of up to half of all patients with Hodgkin and non-Hodgkin lymphoma. This suggests that it may play a role in causing lymphoma. The cancer cells infected by EBV are able to hide from the body's immune system and escape being killed. The investigators previously tested whether special white blood cells (called T cells) that were trained to kill EBV-infected cells could affect these tumors, and in many patients the investigators found that giving these trained T cells caused a complete or partial response.

Other cancers express specific proteins that can be targeted in the same way. The investigators have been able to infuse such tumor-targeted cells into up to 10 patients with lymphoma who do not have EBV, and seen some complete responses. Importantly, the treatment appears to be safe. Therefore, the investigators now want to test whether the investigators can direct these special T cells against other types of cancers that carry similar proteins called tumor-associated antigens (TAAs). These proteins are specific to the leukemia cell, so they either do not show up, or show up in low quantities, on normal human cells.

The investigators will grow T cells from patients' stem cell donors in the laboratory in a way that will train them to recognize the tumor proteins WT1, PRAME and Survivin, which are expressed on most ALL cancer cells. The cells will be infused at least 30 days post-allogeneic HSCT. In this study, the investigators want to see whether these cells will be able to recognize and kill leukemia cells that express these antigens. These donor-derived multiTAA-specific T cells are an investigational product not yet approved by the U.S. Food and Drug Administration.

The purpose of this study is to find the largest safe dose of donor-derived multiTAA-specific T cells for patients with ALL.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

To make donor-derived multiTAA-specific T cells, the investigators will collect blood from the patient's stem cell donor, and mix the donor's T cells with small pieces of the tumor proteins WT1, PRAME and Survivin. These protein fragments stimulate the donor T cells to grow and react against these proteins in such a way that they will recognize and kill cancer cells that express these proteins. Once sufficient numbers of multiTAA-specific T cells have been made, the investigators test them to make sure they target the patient's cancer cells, but not their normal healthy cells.

The multiTAA-specific T cells will be administered as a single intravenous (IV) infusion over 10 minutes. The patient's cancer will be assessed within 4 weeks prior to the T cell infusion, at 4-6 weeks, and again at 8-12 weeks after the infusion. If at least 4 weeks after the infusion there is no change or a reduction in the number of cancer cells measured in the bone marrow, or a decline in cancer-specific markers in the blood, patients may receive up to six (6) additional doses of the T cells at least 4 weeks apart. All of the treatments will be given by the Center for Cell and Gene Therapy at Houston Methodist Hospital or Texas Children's Hospital.

For at least 4 weeks after the infusion, patients may not receive any other anti-cancer treatments, such as radiation therapy or chemotherapy, with the exception of drugs like dasatinib. Patients who do receive any other therapies will be taken off treatment, and will not be able to receive additional doses of T cells.

This is a dose escalation study, which means that at the beginning, patients will be started on the lowest dose (1 of 3 different levels) of T cells. Once that dose level proves safe, the next group of patients will be started at the next highest dose. This process will continue until all 3 dose levels have been studied. If side-effects are too severe, the dose will be lowered or the T cell injections will be stopped.

Before being treated, patients will undergo a series of standard medical tests:

  • Physical exam.
  • Blood tests to measure blood cells, kidney and liver function.
  • Measurement of ALL (done by a bone marrow biopsy or blood tests).
  • Pregnancy test, if patient is a female who can have children.

Patients will undergo standard medical tests both during the T cell infusions and after:

  • Blood tests to measure blood cells, kidney and liver function.
  • Measurement of disease 4-6 weeks and 8-12 weeks after the T cell infusion (done by bone marrow biopsy or blood tests).

Active participation in this study will last for approximately one (1) year. If the patient receives additional doses of the T cells as described above, their active participation will last until one (1) year after the last dose of T cells. We will then contact the patient once a year for up to 4 additional years (total of 5 years follow-up) in order to evaluate disease response long-term.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
40

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • Texas Children's Hospital
      • Houston, Texas, United States, 77030
        • Houston Methodist Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Only patients who receive infusions in the integrated Cell and Gene Therapy (CAGT) Transplant program at Texas Children's Hospital (TCH) or Houston Methodist Hospital (HMH) are eligible for this study.

  1. Patients will be eligible to receive donor-derived multiTAA-specific T cells following any type of allogeneic HSCT as:

    (i) Adjuvant therapy for ALL (Group A), or (ii) Treatment for relapsed/residual ALL disease (Group B)

    Residual disease at the time of transplant or post-transplant relapse is defined as PCR positivity, specific cytogenetic abnormalities, an abnormal population on flow cytometry, or increased blasts on bone marrow biopsy or in the peripheral blood. Minimal residual disease (MRD )will be defined as detection in blood or marrow of any of the following:

    (i) Any leukemia-specific marker (such as t(12;21); t(9;22) or t(4;11)) documented in the patient's leukemia cells pre-transplant on a post-transplant evaluation.

    (ii) A leukemia-specific phenotype (e.g. expression of markers including CD10 and/or CD19 or CD3 and/or CD4 or CD8) post-transplant at a level greater than or equal to 0.01%.

    (iii) Mixed donor chimerism (greater than 20%).

  2. Life expectancy greater than or equal to 6 weeks.
  3. Karnofsky/Lansky score of greater than or equal to 50.
  4. Patient or parent/guardian capable of providing informed consent.
  5. Bilirubin less than or equal to 2X upper limit of normal.
  6. AST less than or equal to 3X upper limit of normal.
  7. Serum creatinine less than or equal to 2X upper limit of normal.
  8. Hgb greater than or equal to 7.0 g/dL (can be transfused).
  9. Pulse oximetry of greater than 90% on room air.
  10. Sexually active patients must be willing to utilize one of the more effective birth control methods for 6 months after the ATL infusion. Male partner should use a condom.
  11. Available donor-derived multiTAA-specific T cell line.
  12. No other investigational anti-neoplastic therapy for one month prior to entry in this study.
  13. Undergoing Stem Cell Transplant at CAGT

Exclusion Criteria:

  1. Patients receiving ATG or Campath within 28 days of infusion.
  2. Patients receiving a Donor Lymphocyte Infusion (DLI) within 4 weeks of planned T cell infusion.
  3. Less than 30 days post-allogeneic stem cell transplant.
  4. Severe intercurrent infection.
  5. Evidence of GVHD greater than Grade II.
  6. Pregnant or lactating.
  7. Currently taking corticosteroids (greater than 0.5 mg/kg/day prednisone or equivalent).

Donor Eligibility:

Donors for allogeneic (i.e. HLA matched or mismatched related or unrelated) stem cell transplants who have fulfilled eligibility for and consented to stem cell donation as per the stem cell transplant program's standard operating procedures. Subjects must be at least 12 kg or 24 pounds to be eligible for stem cell donation. The stem cell donor will have already been selected by the primary Bone Marrow Transplant attending according to CAGT SOPs for Donor Evaluation, Donor Selection, and Donor Deferral. If a donor has been chosen for the transplant based on urgent medical need, that same donor will also be used for T cell generation, provided that there are no new reasons for ineligibility since the stem cell collection. In this study, the subject's hematopoietic stem cell donor will also be the donor for the T cells.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Group A
Treatment with donor-derived multiTAA-specific T cells as adjuvant therapy following HSCT for ALL.
Biological: MultiTAA-specific T cells

The 3 dose levels are:

Dose Level 1: 5 x 10e6 cells/m2; Dose Level 2: 1 x 10e7 cells/m2; Dose Level 3: 2 x 10e7 cells/m2

The T cells are given from 30 days post-HSCT. They are administered by intravenous injection over 1-10 minutes through either a peripheral or a central line.

Patients being treated on Arm A (adjuvant) or Arm B (active disease) who have a partial response, complete response or stable disease, will be eligible to receive up to 6 further doses of multiTAA-specific T cells at the same dose as the initial infusions at a minimum of 4 weeks apart.

Other Names:
  • Multiple tumor-associated antigen (TAA)-specific T cells
Experimental: Group B
Treatment with donor-derived multiTAA-specific T cells for relapsed/residual disease following HSCT for ALL.
Biological: MultiTAA-specific T cells

The 3 dose levels are:

Dose Level 1: 5 x 10e6 cells/m2; Dose Level 2: 1 x 10e7 cells/m2; Dose Level 3: 2 x 10e7 cells/m2

The T cells are given from 30 days post-HSCT. They are administered by intravenous injection over 1-10 minutes through either a peripheral or a central line.

Patients being treated on Arm A (adjuvant) or Arm B (active disease) who have a partial response, complete response or stable disease, will be eligible to receive up to 6 further doses of multiTAA-specific T cells at the same dose as the initial infusions at a minimum of 4 weeks apart.

Other Names:
  • Multiple tumor-associated antigen (TAA)-specific T cells

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of patients with dose-limiting toxicities (DLTs).
Time Frame: 4 weeks
Maximum tolerated dose (MTD) of multiTAA-specific T cells among the three pre-specified dose levels.
4 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of patients with a decrease in the marker of disease.
Time Frame: 4 weeks
To obtain information on the anti-tumor effects of adoptively transferred donor-derived multiTAA-specific T cells in patients with ALL.
4 weeks
Median number of T cells post-infusion.
Time Frame: 1 year
To obtain information on the expansion and persistence of adoptively transferred donor-derived multiTAA-specific T cells in patients with ALL.
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Baylor College of Medicine

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
The Methodist Hospital Research Institute
Center for Cell and Gene Therapy, Baylor College of Medicine

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Bilal Omer, MD, Baylor College of Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 29, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 18, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 12, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 16, 2015

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 19, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 6, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 4, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • H-37042 STELLA
  • STELLA (Other Identifier: Baylor College of Medicine)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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