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Leukemia, AcutePhase 1/2NCT01050764

Haploidentical Allogeneic Transplant With Post-transplant Infusion of Regulatory T-cells

A Phase 1/2 study testing Regulatory T-cells, Conventional T-cells and Melphalan in people with Leukemia, Acute and Chronic Myelogenous Leukemia (CML), run by Everett Meyer at 1 site in United States.

Terminated

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

Official record
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Trial summary

Patients with hematologic malignancies will receive myeloablative chemotherapy followed by stem cell rescue with bone marrow or hematopoietic peripheral blood stem cells collected by apheresis from a filgrastim- (G-CSF)-mobilized haploidentical related-donor, ie, hematopoietic peripheral blood stem cell transplant… Read more about this study

Who is it for?
Ages Up to 60 years
What is being tested?
Regulatory T-cells, Conventional T-cells and Melphalan
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
1 siteUnited States
Study dates
Jun 2009to Jun 2014
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 Up to 60 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • RECIPIENT
  • Histopathologically-confirmed:
  • Acute leukemia (in first remission with poor risk factors and molecular prognosis)
  • Acute myelogenous leukemia (AML) with -5,-7, t (6;9), tri8, -11
  • Acute lymphoblastic leukemia (ALL) with Ph+ t (9;22), t (4;22), (q34;q11)
  • Acute leukemia with refractory disease or > Complete Remission (CR) 1
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  • Chronic myelogenous leukemia (CML) (accelerated, blast or second chronic phase)
  • Myelodysplastic syndrome (in high and high intermediate risk categories)
  • Non-Hodgkin's lymphoma (NHL) with poor risk features and not suitable for autologous transplantation
  • Refractory Chronic lymphocytic leukemia (CLL)
  • At least 21 days from the end of most recent prior therapy to start of the transplant conditioning regimen
  • Must be < 60 years old at time of registration.
  • Karnofsky Performance Status (KPS) > 70%
  • Must have related donor who is:
  • Genotypically human leukocyte antigen (HLA) -A, B,C and DR beta 1 (DRB1), DQ loci haploidentical to the recipient (but differing for 2 to 3 HLA alleles on the unshared haplotype in the graft-versus-host disease (GvHD) direction)
  • No HLA-matched sibling or matched-unrelated donor is identified.
  • Adequate cardiac and pulmonary function (left ventricular ejection fraction (LVEF) > 45%, diffusing capacity of the lungs for carbon monoxide (DLCO) >50% corrected for hemoglobin)
  • Serum creatinine < 1.5 mg/dL OR Creatinine clearance > 50 mL/min for those above serum creatinine at least 1.5 mg/dL
  • Serum bilirubin < 2.0 mg/dL
  • Alanine transaminase (ALT) < 2x upper normal limit (ULN) (unless secondary to disease)
  • No prior myeloablative therapy or hematopoietic cell transplantation
  • DONOR:
  • Age ≤ 70 years
  • Weight ≥ 25 kg.
  • Medical history and physical examination confirm good health status as defined by institutional standards
  • Seronegative for HIV Ag within 30 days of apheresis collection for:
  • Hepatitis B surface antigen (sAg) or polymerase chain reaction (PCR) +
  • Hepatitis C ab or PCR+
  • Genotypically haploidentical as determined by HLA typing
  • Female donors (child-bearing potential) must have a negative serum or urine beta-human chorionic gonadotropin (HCG) test within 3 weeks of mobilization
  • Capable of undergoing leukapheresis
  • Has adequate venous access
  • Willing to undergo insertion of a central catheter if leukapheresis via peripheral vein is inadequate
  • Capable of agreeing to second donation of peripheral blood progenitor cell (PBPC) (or a bone marrow harvest) should the patient fail to demonstrate sustained engraftment following the transplant
  • Institutional review board (IRB)-approved consent form signed by donor or legal guardian > 18 years of age
  • Donor Selection in the priority order:
  • Recipient's biological mother preferred, if available
  • Other available haploidentical donors will be selected based upon the presence of natural killer (NK) alloreactivity between donor and recipient by high-resolution HLA typing of the C locus. An NK-alloreactive donor will be preferentially chosen. Recipients lacking a killer immunoglobulin-like receptor (KIR)-ligand present in the donor along with the corresponding KIR defines "NK alloreactivity".
  • If more than one NK-alloreactive donor is available, preference is to cytomegalovirus (CMV)-seronegative donor

Who cannot join

  • RECIPIENT:
  • Suitable candidate for autologous transplantation or allogeneic transplantation with an available matched-related or matched-unrelated donor
  • Seropositive for:
  • HIV ab
  • Hepatitis B sAg or PCR+
  • Hepatitis C ab or PCR+
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  • History of invasive Aspergillosis
  • Any active, uncontrolled bacterial, viral or fungal infection
  • Uncontrolled central nervous system (CNS) disease involvement
  • Lactating female
  • DONOR:
  • Evidence of active infection or viral hepatitis
  • Factors of increased risk for complications from leukapheresis or granulocyte-colony stimulating factor (G-CSF) therapy
  • Lactating female
  • HIV-positive

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: A Feasibility Trial of Post-Transplant Infusion of Allogeneic Regulatory T Cells and Allogeneic Conventional T Cells in Patients With Hematologic Malignancies Undergoing Allogeneic Myeloablative Hematopoietic Cell Transplantation From Haploidentical-Related Donors

Patients with hematologic malignancies will receive myeloablative chemotherapy followed by stem cell rescue with bone marrow or hematopoietic peripheral blood stem cells collected by apheresis from a filgrastim- (G-CSF)-mobilized haploidentical related-donor, ie, hematopoietic peripheral blood stem cell transplant (HSCT).

Read the detailed description

This is dose-escalation study intended to evaluate the use of classification determinant 15-positive (CD15+), CD4+, CD127dim, and FoxP3+ regulatory T-cells (T-reg cells) supplemented by conventional T-cells (T-con cells), to enhance the efficacy of allogeneic (CliniMACS CD34+ selected) hematopoietic stem cell transplantation (allo-HSCT), in the setting of leukemia, lymphoma, and myelodysplastic syndrome (MDS). This study investigates amelioration of the impaired immune recovery and address the significant relapse incidence in the haploidentical HSCT setting.

Pre-transplant myeloablative conditioning will be melphalan; thiotepa; fludarabine and rabbit antithymocyte globulin (rATG).

Stem cell rescue will be with CD34+ selected cells. The rescue infusion will be supplemented with infusions of regulatory T-cells (T-reg) and conventional T-cells (T-con) from the same donor collection, on Treatment Days 14 and 16 respectively. CD34+ cell infusion day is Treatment Day 0.

T-reg cells are those cells enriched by immunomagnetic selection of CD25+ cells, and further purified by flow cytometric cell sorting for the CD15+, CD4+, CD127dim, FoxP3+ cell population. These cells are an enriched but naturally-occurring T-cell population.

T-con cells are unseparated/unfractionated cells, ie, as collected by the peripheral blood stem cells apheresis procedure.

Post-transplant follow-up is for 5 years.

Being tested
Regulatory T-cells, Conventional T-cells, Melphalan, Thiotepa, Fludarabine
Medical subject headings
Leukemia, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Myelodysplastic Syndromes, Lymphoma, Non-Hodgkin, Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

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

  • Regulatory T-cellsDrug

    Also called T-reg cells

    To ameliorate the impaired immune recovery and address the significant relapse incidence in the haploidentical setting. Cells will be selected by a tandem selection process and infused on day +14. These are the enriched but naturally-occurring regulatory T cells. Possible dose cohorts and levels are:

    Cohort 1

    • T-reg: 1 x 10e5/kg
    • T-con: 3 x10e5/kg

    Cohort 2

    • T-reg: 3 x 10e5/kg
    • T-con: 1 x 10e6/kg

    Cohort 3

    • T-reg: 1 x 10e6/kg
    • T-con: 3 x 10e6/kg

    Cohort 4

    • T-reg: 3 x 10e6/kg
    • T-con: 1 x 10e7/kg
  • Conventional T-cellsDrug

    Also called T-con cells

    These are conventional (unselected) donor T-cells. Cell dosage of the infusion will be based on the CD3+ cell content and infused on day +16.

  • MelphalanDrug

    Also called L-PAM, L-Sarcolysin, Phenylalanine Mustard

    Anti-cancer chemotherapy drug administered IV at 140 mg/m² on Day -8 prior to HSCT (a component of the conditioning regiment prior to infusion of cells)

  • ThiotepaDrug

    Also called thiophosphamide, TESPA, TSPA

    Anti-cancer chemotherapy drug administered IV at 10 mg/kg on Day -7 prior to HSCT (a component of the conditioning regiment prior to infusion of cells)

  • FludarabineDevice

    Also called Fludarabine phosphate, Fludarabine 5'-monophosphate, FAMP, Fludara

    Anti-cancer chemotherapy drug administered IV at 160mg/m² on Days -6; -5; -4; and -3 prior to HSCT (a component of the conditioning regiment prior to infusion of cells

  • Anti-thymocyte globulin, rabbitDrug

    Also called Thymoglobulin, rATG

    Rabbit-derived antibodies against human T-cells used as transplant rejection prophylaxis. Administered at 6 mg/kg IV on Days -6; -5; -4; and -3 prior to HSCT

  • CliniMACS CD34 Reagent SystemDrug

    An in vitro medical device system that uses antibodies conjugated to magnetic beads to select and enrich for CD34+ blood stem cells from the allogeneic donor apheresis product prior to HSCT, while removing other cells that can cause GvHD. CD34+ cell dosage will be based on the participant's body weight.

Study groups in NCT01050764
Study groupRoleWhat they receive
T-reg Cell Infusion after Allogeneic Stem Cell TransplantExperimentalNot described
Receives: Drug: Regulatory T-cells; Drug: Conventional T-cells; Drug: Melphalan; Drug: Thiotepa; Device: Fludarabine; Drug: Anti-thymocyte globulin, rabbit; Drug: CliniMACS CD34 Reagent System

What is being measured

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

  1. Maximum-tolerated Dose (MTD) of Regulatory and Conventional T-cells

    The maximum-tolerated dose (MTD) was to be determined based on the safety and feasibility observed for a pre-determined set of cellular dose level combinations of regulatory T-cells (T-reg) and conventional T-cells (T-con).

    Measured: 30 days after HSCT infusion

Secondary outcomes (5)
  1. Acute Graft-versus-Host-Disease (aGvHD)

    The primary outcome was incidence of grade 3 or 4 acute graft-vs-host-disease (aGvHD), reported as the number of participants developing grade 3 or 4 aGvHD.

    Measured: 1 year

  2. Overall Survival (OS), 1 Year

    Assessed as subjects remaining alive 12 months after CD34+ cell infusion (ie, excludes death due to any cause)

    Measured: 1 year

  3. Median Overall Survival (OS)

    Reported as the median overall survival (OS) in months from infusion of the hematopoietic stem cells (HSCT)

    Measured: 25 months

  4. To Measure the Incidence and Severity of Acute and Chronic GvHD

    Population of participants that received HSCT and T-reg plus T-con, and developed actue, chronic, or any graft vs host disease (GvHD)

    Measured: 1 year

  5. Serious Infections

    Serious infections are reported as the number of participants experienced serious infections.

    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 posted15 Jan 2010 (estimated)
  2. Study startJun 2009
  3. Primary completionAug 2012
  4. Study completionJun 2014

Why it stopped: Safety

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01050764
Sponsor's protocol ID
IRB-15919
Other IDs
BMT204, SU-03312009-2059
Status last verified
Jun 2018
First submitted
11 Jan 2010
Last updated
27 Jun 2018
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 1/2 study testing Regulatory T-cells, Conventional T-cells and Melphalan in people with Leukemia, Acute and Chronic Myelogenous Leukemia (CML), run by Everett Meyer 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 39 inclusion and 15 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 27 Jun 2018. 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 11 May 2017). 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?

Maximum-tolerated Dose (MTD) of Regulatory and Conventional T-cells (time frame: 30 days after HSCT infusion). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 27 Jun 2018.

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