AzTrials
AzTrials

Recurrent Adult Acute Myeloid LeukemiaPhase 1/2NCT01640301

Laboratory-Treated T Cells in Treating Patients With High-Risk Relapsed Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Chronic Myelogenous Leukemia Previously Treated With Donor Stem Cell Transplant

A Phase 1/2 study testing Aldesleukin, Cyclophosphamide and Fludarabine Phosphate in people with Recurrent Adult Acute Myeloid Leukemia and Recurrent Childhood Acute Myeloid Leukemia, run by Fred Hutchinson Cancer Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

This phase I/II trial studies the side effects of laboratory-treated T cells and to see how well they work in treating patients with high-risk acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myelogenous leukemia (CML) that has returned after a period of improvement (relapsed), previously… Read more about this study

Who is it for?
Any age
What is being tested?
Aldesleukin, Cyclophosphamide and Fludarabine Phosphate
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
47 participants
Where
1 siteUnited States
Study dates
6 Dec 2012to 20 Mar 2020
Phase
Phase 1/2
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 Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Patients must express HLA-A*0201
  • Patients who are currently undergoing or who previously underwent matched allogeneic HCT for:
  • AML: Prospective enrollment will now be limited to patients with relapsed disease (overt relapse or minimal residual disease) at any time post allogeneic HCT
  • MDS will no longer be a criterion for eligibility
  • CML will no longer be a criterion for eligibility
  • Patients must have an HLA-matched donor of hematopoietic stem cells (related or unrelated)
Show all 14Show fewer
  • Patients must be able to provide blood and bone marrow samples and undergo the procedures required for this protocol
  • Patients must be >= 15 kg, as patients with lower weight would be incapable of providing high volume and frequent blood samples for monitoring and analysis
  • Patients must be able to give informed consent; parent or legal representative will be asked to consent for patients younger than 18 year old
  • DONOR: Patient and donor (related or unrelated) must be HLA-matched and express HLA-A*0201
  • DONOR: Donor must be Epstein-Barr virus (EBV) or cytomegalovirus (CMV) seropositive
  • DONOR: Donor must be age 18 or older
  • DONOR: In good general health
  • DONOR: Able to give informed consent

Who cannot join

  • Central nervous system (CNS) tumor refractory to intrathecal chemotherapy and/or cranio-spinal radiation
  • In patients whose leukemic cells are available for evaluation, the expression of WT1 in the patient's bone marrow will be determined; if WT1 expression in the patient's bone marrow is not highly expressed by polymerase chain reaction (PCR), the patient will be excluded from the study; patients with no evaluable leukemia will be eligible for enrollment based on the high frequency of positive leukemias (> 90%), and leukemia will be evaluated for WT1 expression if recurrence is detected
  • Human immunodeficiency virus (HIV) seropositive; testing for HIV should be within 6 months of enrollment
  • Medical or psychological conditions that would make the patient unsuitable candidate for cell therapy at the discretion of the principal investigator (PI)
  • Pregnancy or breast-feeding; women of childbearing potential must have a negative serum or urine beta-human chorionic gonadotropin (B-hCG) pregnancy test result within 14 days before the first dose of WT1-specific T cell infusion; woman of non-childbearing potential will be defined as being postmenopausal greater than one year or who have had a bilateral tubal ligation or hysterectomy; all recipients of WT1-specific T cells will be counseled to use effective birth control during participation in this study and for 12 months after the last T cell infusion
  • DONOR: Less than 18 years old
Show all 11Show fewer
  • DONOR: Active infectious hepatitis
  • DONOR: HIV or human T-lymphotropic virus (HTLV) seropositive
  • DONOR: Pregnancy or nursing
  • DONOR: Significant medical conditions (e.g. immunosuppressive therapy) that would make the donor an unsuitable T cell donor
  • DONOR: Unable to give informed consent

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: Phase I/II Study of Adoptive Immunotherapy After Allogeneic HCT With Virus Specific CD8+ T Cells That Have Been Transduced to Express a WT1-Specific T Cell Receptor for Patients With Relapsed AML

This phase I/II trial studies the side effects of laboratory-treated T cells and to see how well they work in treating patients with high-risk acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myelogenous leukemia (CML) that has returned after a period of improvement (relapsed), previously treated with donor stem cell transplant. Biological therapies, such as cellular adoptive immunotherapy, may stimulate the immune system in different ways and stop cancer cells from growing. Placing a gene that has been created in the laboratory into a person's T cells may make the body build an immune response to kill cancer cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine the safety and potential toxicities associated with treating patients with high risk or relapsed AML, MDS, and CML after allogeneic hematopoietic cell transplantation (HCT) by adoptive transfer of virus-specific cluster of differentiation (CD)8 T cells genetically-modified to express a high affinity Wilms tumor 1 (WT1)-specific T cell receptor (TCR).

II. Determine the anti-leukemic activity associated with treating patients with relapsed AML, MDS and CML after allogeneic HCT by adoptive transfer of virus-specific CD8 T cells genetically-modified to express a high affinity WT1-specific T cell receptor (TCR).

SECONDARY OBJECTIVES:

  1. Determine the in vivo persistence of transferred T cells and ability to migrate to and accumulate in bone marrow.

II. Determine the maintenance of TCR expression and function of transduced T cells.

OUTLINE: Patients are assigned to 1 of 2 treatment arms.

ARM I: Patients with no evidence of leukemia post-HCT receive WT1-sensitized T cells intravenously (IV) over 45 minutes (or longer for patients who are 15-30 kg) on days 0 and 14 and aldesleukin subcutaneously (SC) twice daily (BID) on days 14-28.

ARM II: Patients with evidence of AML (minimal residual disease or overt relapse) post-HCT receive cyclophosphamide IV and fludarabine phosphate IV daily on days -4 to -2. Patients also receive WT1-sensitized T cells IV over 45 minutes (or longer for patients who are 15-30 kg) on days 0 and 21 and aldesleukin SC BID on days 14-28.

After completion of study treatment, patients are followed up weekly for 4 weeks, at weeks 6 and 8, at 3, 6, 12 months, and then annually for up to 15 years.

Being tested
Aldesleukin, Cyclophosphamide, Fludarabine Phosphate, Laboratory Biomarker Analysis, WT1-Sensitized Allogeneic T-Lymphocytes
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

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

  • AldesleukinBiological

    Also called 125-L-Serine-2-133-interleukin 2, Proleukin, r-serHuIL-2, Recombinant Human IL-2

    Given SC

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • Fludarabine PhosphateDrug

    Also called 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • WT1-Sensitized Allogeneic T-LymphocytesBiological

    Given IV

Study groups in NCT01640301
Study groupRoleWhat they receive
Arm I (high-risk for relapse after HCT)ExperimentalPatients with no evidence of leukemia or MDS post-HCT receive WT1-sensitized T cells IV over 45 minutes (or longer for patients who are 15-30 kg) on days 0 and 14 and aldesleukin SC BID on days 14-28.
Receives: Biological: Aldesleukin; Other: Laboratory Biomarker Analysis; Biological: WT1-Sensitized Allogeneic T-Lymphocytes
Arm II (relapsed after HCT)ExperimentalPatients with evidence of AML (minimal residual disease or overt relapse) post-HCT receive cyclophosphamide IV and fludarabine phosphate IV daily on days -4 to -2. Patients also receive WT1-sensitized T cells IV over 45 minutes (or longer for patients who are 15-30 kg) on days 0 and 21 and aldesleukin SC BID on days 14-28.
Receives: Biological: Aldesleukin; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Biological: WT1-Sensitized Allogeneic T-Lymphocytes

What is being measured

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

  1. Anti-leukemic Potential Efficacy, in Terms of Duration of Response (Arm II)

    Response is assessed throughout the 1 year post treatment timeframe. Morphologic criteria for response:

    Complete Response (CR) = Bone Marrow blasts <5%; no blasts with Auer rods; no extramedullary disease. Transfusion independent.

    Platelets ≥ 100,000/μl Absolute neutrophil count >1000/μl (CRi: incomplete hematologic recovery CRp: incomplete platelet recovery)

    Partial Response (PR) = Decrease of at least 50% in the percentage of blasts to 5-25% in the bone marrow and the normalization of blood counts as for CR. (PRi and PRp if incomplete hematologic or platelet recovery)

    Stable Disease (SD) = Failure to achieve at least PR, but no evidence of progression for >4 weeks.

    Measured: Up to 1 year

  2. Efficacy, in Terms of Relapse Rate (Arm I)

    Measured: At 1 year post-transplant

  3. Count of Participants Who Experienced Chronic Graft Versus Host Disease (GVHD) (Arm I)

    Measured: Up to 1 year

  4. Count of Participants Who Experienced Chronic Graft Versus Host Disease (GVHD) (Arm II)

    Measured: Up to 1 year

  5. Count of Participants Who Experienced Grade III-IV Acute Graft Versus Host Disease (GVHD) (Arm II)

    Measured: Up to 1 year following infusion per patient

  6. Count of Participants Who Experienced Grade III-IV Acute Graft-versus-host Disease (GVHD) (Arm I)

    Measured: Up to 1 year

  7. Treatment-related Toxicity Rate (Arm I)

    Outcome will be reported as a count of participants that experienced adverse events. Toxicity will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 4.0

    Measured: Up to 30 days after last study intervention per patient

  8. Treatment-related Toxicity Rate (Arm II)

    Outcome will be reported as a count of participants that experienced adverse events. Toxicity will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 4.0

    Measured: Up to 30 days after last study intervention per patient

Secondary outcomes (5)

  1. Disease-free Survival After T Cell Therapy

    Measured: Up to 1 year

  2. Incidence of Relapse After T Cell Therapy (Arm II)

    Measured: Up to 1 year

  3. Maintenance of T Cell Receptor (TCR) Expression of Transduced T Cells (Arm I) i.e. Persistence

    Measured: Up to 28 days post intervention per patient

  4. Maintenance of Function of Transduced T Cells (Arm I)

    Measured: Up to 28 days post intervention per patient

  5. Time to Progression After T Cell Therapy (Arm I)

    Measured: Up to 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 posted13 Jul 2012 (estimated)
  2. Study start6 Dec 2012
  3. Primary completion20 Mar 2020
  4. Study completion20 Mar 2020

Why it stopped: Terminated due to slow accrual.

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
47 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01640301
Sponsor's protocol ID
2498.00
Other IDs
NCI-2011-03362, 2498, 2498.00, P01CA018029, RG9212029
Status last verified
Jun 2022
First submitted
29 Nov 2011
Last updated
14 Jul 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Chapuis AG, Egan DN, Bar M, Schmitt TM, McAfee MS, Paulson KG, Voillet V, Gottardo R, Ragnarsson GB, Bleakley M, Yeung CC, Muhlhauser P, Nguyen HN, Kropp LA, Castelli L, Wagener F, Hunter D, Lindberg M, Cohen K, Seese A, McElrath MJ, Duerkopp N, Gooley TA, Greenberg PD. T cell receptor gene therapy targeting WT1 prevents acute myeloid leukemia relapse post-transplant. Nat Med. 2019 Jul;25(7):1064-1072. doi: 10.1038/s41591-019-0472-9. Epub 2019 Jun 24.

    PubMed 31235963

  • Oda SK, Daman AW, Garcia NM, Wagener F, Schmitt TM, Tan X, Chapuis AG, Greenberg PD. A CD200R-CD28 fusion protein appropriates an inhibitory signal to enhance T-cell function and therapy of murine leukemia. Blood. 2017 Nov 30;130(22):2410-2419. doi: 10.1182/blood-2017-04-777052. Epub 2017 Oct 17.

    PubMed 29042364

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Aldesleukin, Cyclophosphamide and Fludarabine Phosphate in people with Recurrent Adult Acute Myeloid Leukemia and Recurrent Childhood Acute Myeloid Leukemia, run by Fred Hutchinson Cancer Center 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 14 inclusion and 11 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: stopped early, as of the sponsor's last update on 14 Jul 2022. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 23 Jun 2022). 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?

Anti-leukemic Potential Efficacy, in Terms of Duration of Response (Arm II) (time frame: Up to 1 year). The study lists 8 primary outcomes in all. 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 NCT01640301, which also lists 2 linked publications.

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 14 Jul 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in