Mismatched Donor Cells to Treat Acute Myeloid Leukemia (ATAC-AML-01)

August 28, 2017 updated by: Elizabeth Krakow, Maisonneuve-Rosemont Hospital

Adoptive Transfer of Alloreactive Cells to Treat Patients With Poor-Prognosis Acute Myeloid Leukemia-01

The purpose of this study is to assess the safety and efficacy of infusing immune cells from a donor as treatment for patients with acute myeloid leukemia that is resistant to chemotherapy or who have experienced relapse. Unlike standard bone marrow or stem cell transplantation which uses donors who are well 'matched' to the patient, this study uses donors whose immune cells are not compatible with the patient. With standard stem cell or bone marrow transplantation, the well-matched immune cells will attack the leukemia but they also attack the patient's organs (a situation called graft-versus-host disease, which can persist in the long term). Our hypothesis is that the mismatched donor cells will fight the leukemia but will then be eliminated from the patient's body, so long-term side effects like graft-versus-host disease should not occur.

Study Overview

Status

Status

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

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

The ATAC cell therapy product contains unselected, non-mobilized peripheral blood mononuclear cells from related donors who are mismatched to the recipients at 3 or more (out of 6) HLA loci. Cohorts of 3 patients will be treated at each of four pre-specified dose levels (T cells per kg recipient weight). One ATAC infusion is administered 24-48 hours following re-induction chemotherapy (for relapsed or primary refractory AML patients not in remission). In situations where ATAC infusion is not available immediately following re-induction chemotherapy and patients nonetheless achieve complete remission, one ATAC infusion is given 24-48 hours after consolidation chemotherapy.

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 (Anticipated)

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.
12

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 Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Canada
    • Quebec
      • Montreal, Quebec, Canada, H1T 3M4
        • Recruiting
        • Hopital Maisonneuve-Rosemont

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Recipient Inclusion Criteria:

  • Age ≥ 18 years (no upper age limit, but physician discretion is advised)
  • AML that is refractory to 2 courses of induction therapy (that together constitute the 'first-line' therapy) or that has relapsed after a period of morphologic complete remission or morphologic remission with incomplete blood count recovery (CRi)
  • Candidacy for intense induction chemotherapy (ECOG 0-2, adequate renal, liver and cardiac function, absence of uncontrolled infections)
  • Availability of parents, siblings or children who are HLA haploidentical (and not homozygous for the shared haplotype), who are deemed suitable donors after medical evaluation, and who complete peripheral blood mononuclear cell collection
  • No history of autologous or allogeneic stem cell transplant, purine analog chemotherapy or cyclophosphamide, or total body irradiation
  • Ability to comprehend the investigational nature of the study and provide informed consent

Recipient Exclusion Criteria:

  • Acute promyelocytic leukemia (including those with non-classical rearrangements of RARα)
  • History of severe myelodysplastic syndrome clearly preceding the diagnosis of AML (i.e., red cell transfusion dependence or erythropoietin dependence over a 4-month period, or in the absence of a clear cause, any of the following: hemoglobin consistently below 9 g/dL or platelets below 50 x 10^9/L or ANC below 1000/uL on 2 or more occasions 2 weeks apart, or use of G-CSF to maintain the ANC threshold in the absence of infection, in the 3 months preceding the diagnosis of AML). Exception: If ATAC therapy is being considered as a bridge to stem cell transplantation in patients with an available standard transplant donor (familial, unrelated, or cord blood), this exclusion criterion does not apply.
  • Grade 2-3/3 fibrosis in the diagnostic bone marrow biopsy
  • DLCO < 40% predicted
  • Left ventricular ejection fraction < 40% (evaluated by ECHO or MUGA)
  • AST/SGOT > 2.5 x ULN
  • Bilirubin > 1.5 x ULN
  • Creatinine > 1.5 x ULN
  • Creatinine clearance < 50 mL/min
  • HIV positive
  • Major anticipated illness or organ failure incompatible with survival from chemotherapy
  • Concurrent second primary cancer or a prior malignancy that required cytotoxic treatment within the past 12 months, other than cervical carcinoma in-situ or prostate cancer in-situ
  • Severe psychiatric illness or mental deficiency sufficiently severe as to make compliance with the treatment unlikely and informed consent impossible
  • Any congenital or acquired immunodeficiency that would possibly permit permanent engraftment of donor cells
  • Receiving systemic steroid therapy or systemic immunosuppression such as cyclosporine or TNF-inhibitors
  • Prior or concurrent receipt of any marketed or investigational agent deemed on an ad hoc basis to cause immunomodulation, pose a threat of permanent engraftment or increase the risk of GVHD.

Donor inclusion criteria:

  • Mismatched family donor (incompatibility at 3 loci HLA-A, B and DR of the unshared haplotype, or higher-order incompatibility)
  • Age ≥ 16 and ≤ 80 years
  • Fit to undergo apheresis (normal blood counts, normotensive and no history of stroke).
  • Donor has been tested negative for HIV-1, HIV-2, hepatitis B virus (HBV, surface and core antigen), hepatitis C virus, human T-lymphotropic virus types I/II, and Treponema pallidum (syphilis).
  • ECOG performance status of 2 or less.
  • Adequate veins for leukapheresis or agree to placement of a temporary central venous catheter.
  • Donor must provide written informed consent.
  • Where multiple equally-suitable donors are available, sex mismatched donors will be preferred.

Donor exclusion criteria:

  • Medically uncontrolled coronary heart disease
  • Myocardial infarction within the last 3 months
  • History of seizure
  • History of stroke
  • History of malignancy (except basal cell or squamous carcinoma of the skin, or positive PAP smear and subsequent negative follow-up)
  • Presence of a transmissible disease (such as HIV seropositivity)
  • Presence of a major illness or a suspected systemic dysfunction
  • Presence of an an active inflammatory or autoimmune disorder
  • Female donors who are pregnant or nursing

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: N/A
  • 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: ATAC Therapy
Biological: ATAC Therapy
Unselected peripheral blood mononuclear cells given 24-48 hours after induction or consolidation chemotherapy
Other Names:
  • Unselected Peripheral Blood Mononuclear 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
Safety
Time Frame: 60 days (up to 2 years)
Maximum tolerated cell dose: Dose at which < 33% of patients experienced dose-limiting toxicity. If no DLT occurs, then dose titration will stop at a pre-specified number of T cells/kg. Four dose-level cohorts are planned.
60 days (up to 2 years)

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
Time Frame
Treatment-related mortality
Time Frame: Continuous up to 2 years
Continuous up to 2 years
Non-relapse mortality
Time Frame: Continuous up to 2 years
Continuous up to 2 years
Incidence of graft-versus-host disease
Time Frame: Continuous up to 2 years
Continuous up to 2 years
Duration of cytopenias
Time Frame: Monitored continuously from ATAC infusion until peripheral blood count recovery or maximum 2 years (whichever is earlier)
Monitored continuously from ATAC infusion until peripheral blood count recovery or maximum 2 years (whichever is earlier)
Overall survival
Time Frame: Continuous up to 2 years
Continuous up to 2 years
Complete and incomplete remissions (CR, CRi)
Time Frame: Day 60 post cell infusion
Day 60 post cell infusion
Relapse-free survival
Time Frame: Continuous up to 2 years
Continuous up to 2 years

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.
Maisonneuve-Rosemont Hospital

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.
  • Study Chair: Jean-Sébastien Delisle, MD,PhD, Hôpital Maisonneuve-Rosemont and Université de Montréal
  • Principal Investigator: Elizabeth Krakow, MD, Hôpital Maisonneuve-Rosemont and Université de Montréal

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.
September 1, 2012

Primary Completion (Anticipated)

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.
December 1, 2018

Study Completion (Anticipated)

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.
December 1, 2018

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).
February 10, 2013

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.
February 13, 2013

First Posted (Estimate)

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.
February 15, 2013

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.
August 30, 2017

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.
August 28, 2017

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.
August 1, 2017

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.
  • ATAC-AML-01

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.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings