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Accelerated Phase Chronic Myelogenous LeukemiaPhase 1/2NCT00052598

Therapeutic Allogeneic Lymphocytes and Aldesleukin in Treating Patients With High-Risk or Recurrent Myeloid Leukemia After Undergoing Donor Stem Cell Transplant

A Phase 1/2 study testing therapeutic allogeneic lymphocytes, aldesleukin and laboratory biomarker analysis in people with Accelerated Phase Chronic Myelogenous Leukemia and Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome, 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
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Trial summary

This phase I/II trial is studies the side effects of giving therapeutic allogeneic lymphocytes together with aldesleukin and to see how well it works in treating patients with high-risk or recurrent myeloid leukemia after undergoing donor stem cell transplant. Read more about this study

Who is it for?
Any age
What is being tested?
therapeutic allogeneic lymphocytes, aldesleukin and laboratory biomarker analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
7 participants
Where
1 siteUnited States
Study dates
Sep 2002to Jun 2011
Phase
Phase 1/2
Are there results?
None posted in the registry

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 undergoing allogeneic hematopoietic stem cell transplantation for chronic myelogenous leukemia (CML) in accelerated or blast phase, acute myeloid leukemia (AML) beyond first remission, primary refractory AML, therapy-related AML at any stage, or acute leukemia at any stage arising in a patient with an antecedent diagnosis of a myelodysplastic or myeloproliferative syndrome (including chronic myelomonocytic leukemia, CML, polycythemia vera, essential thrombocytosis, and agnogenic myeloid metaplasia with myelofibrosis)
  • Patients and donors must both be human leukocyte antigen (HLA)-A2 positive
  • Patients must be able to provide blood and bone marrow samples required for this protocol
  • Eligibility for Prophylactic Treatment with CD8+ CTL After Transplant (Highest Risk Subgroup):
  • At time of planned treatment, CD8+ CTL specific for PR3 must have been generated and have completed Quality Control (QC) testing
  • Patients must have had > 5% morphologic blasts detectable in bone marrow or peripheral blood just prior to or at the time of transplant
Show all 16Show fewer
  • Patients must have evidence of posttransplant recovery of normal hematopoiesis (absolute neutrophil count [ANC] > 500/mm^3) for at least 7 days prior to the initiation of CTL infusions
  • Patients on immunosuppressive therapy for graft-versus-host disease (GVHD) are eligible for treatment if not receiving corticosteroids or if the dose of corticosteroids can be tapered to < the equivalent of 0.5 mg/kg/day of prednisone; The patient's symptoms have to remain stable and unlikely to increase to stage III or IV acute GVHD or chronic GVHD is unlikely to progress following the change in immunosuppressive therapy, after an appropriate monitoring period, as deemed by the patients treating physician and the principal investigator
  • Eligibility for Treatment with CD8+ CTL at the Time of Relapse After Transplant (All Others):
  • At time of planned treatment, CD8+ CTL specific for PR3 must have been generated and have completed Quality Control (QC) testing
  • Patients must have evidence of recurrent/progressive disease posttransplant
  • Morphologic relapse defined as one or more of the following: abnormal peripheral blasts in absence of growth factor therapy, abnormal bone marrow blasts > 5% of nucleated cells, extramedullary chloroma or granulocytic sarcoma
  • Flow cytometric relapse defined as the appearance in the peripheral blood or bone marrow of cells with an abnormal immunophenotype detected by flow cytometry that is consistent with leukemia recurrence/progression
  • Cytogenetic relapse/progression defined as the appearance in one or more metaphases from bone marrow or peripheral blood cells of either a non-constitutional cytogenetic abnormality identified in at least one cytogenetic study performed prior to transplant or a new abnormality known to be associated with leukemia; (for CML), an increase in the number of Ph+ metaphases from bone marrow or peripheral blood between two consecutive samples after engraftment, or an increase in the percentage of BCR/ABL+ cells by fluorescence in situ hybridization (FISH) between two consecutive samples after engraftment
  • Molecular relapse/progression defined as a polymerase chain reaction (PCR) assay of bone marrow (BM) or peripheral blood mononuclear cells (PBMC) positive for the presence of the BCR/ABL messenger ribonucleic acid (mRNA) fusion transcript that quantitatively increases by greater than one order of magnitude on a subsequent sample
  • Patients on immunosuppressive therapy for GVHD at the time of relapse are eligible for treatment if not receiving corticosteroids or if the dose of corticosteroids can be tapered to < the equivalent of 0.5 mg/kg/day of prednisone; the patient's symptoms have to remain stable and unlikely to increase to stage III or IV acute GVHD or chronic GVHD is unlikely to progress following the change in immunosuppressive therapy, after an appropriate monitoring period, as deemed by the patient's treating physician and the principal investigator

Who cannot join

  • Exclusions for Treatment at the Time of Relapse/Progression After Transplant:
  • Patients for whom CD8+ CTL clones specific for PR3 have not been generated by the time of disease relapse/progression post-transplant; these patients can potentially be treated later if CTL become available; patients whose malignant cells do not overexpress PR3, based on direct analysis of a bone marrow sample with > 50% blasts or of leukemia cells isolated for expression analysis; in either case, patients will be informed about the availability of other treatment protocols for which they might be eligible
  • Patients with Karnofsky performance status or Lansky play score =< 30%
  • Patients with current stage III or IV GVHD unresponsive to therapy or requiring therapy with anti-CD3 mAb, prednisone > 0.5 mg/kg/day (or corticosteroid equivalent), or other treatments resulting in the ablation or inactivation of T cells (such as other anti-T cell monoclonal antibodies); although the concurrent use of cyclosporine, FK506, or mycophenolate mofetil (MMF) is not strictly an exclusion criterion, attempts should be made to discontinue it if possible
  • Patients requiring concurrent therapy with hydroxyurea or other agents that may interfere with the function or survival of infused CTL clones
  • Patients with a preexisting nonhematopoietic organ toxicity that is deemed by the principal investigator to place the patient at unacceptable risk for treatment on the protocol
  • Patients with graft rejection or failure

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Fred Hutchinson Cancer Research Center/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 With CD8+ Proteinase 3 (Myeloblastin)-Specific CTL Clones for HLA-A2+ Patients With Relapse or Progression of Disease After Allogeneic Hematopoietic Stem Cell Transplant for High Risk Myeloid Leukemias

This phase I/II trial is studies the side effects of giving therapeutic allogeneic lymphocytes together with aldesleukin and to see how well it works in treating patients with high-risk or recurrent myeloid leukemia after undergoing donor stem cell transplant. Biological therapies, such as therapeutic autologous lymphocytes, may stimulate the immune system in different ways and stop cancer cells from growing. Aldesleukin may stimulate the white blood cells to kill cancer cells. Giving therapeutic autologous lymphocytes together with aldesleukin may kill more cancer cells

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the safety and potential toxicities associated with infusing donor CD8+ cytotoxic T lymphocytes (CTL) clones specific for Proteinase 3 (Myeloblastin) in patients with relapse/progression of high risk myeloid leukemias after transplant.

SECONDARY OBJECTIVES:

  1. To determine the in vivo persistence of transferred T cells and assess migration to the bone marrow, a predominant site of leukemic relapse.

II. To determine if adoptively transferred proteinase 3 (PR3)-specific T cells mediate antileukemic activity.

OUTLINE:

Patients receive allogeneic CD8+ PR3-specific CTLs intravenously (IV) over 1-2 hours on days 0, 7, 14, 28, and 49 and aldesleukin subcutaneously (SC) twice daily on days 28-41 and 49-63 in the absence of unacceptable toxicity.

After completion of study treatment, patients are followed up every 1-3 months.

Being tested
therapeutic allogeneic lymphocytes, aldesleukin, laboratory biomarker analysis, flow cytometry
Medical subject headings
Leukemia, Myeloid, Accelerated Phase, Congenital Abnormalities, Blast Crisis, Leukemia, Myeloid, Acute

What participants receive

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

  • therapeutic allogeneic lymphocytesBiological

    Also called ALLOLYMPH

    Given IV

  • aldesleukinBiological

    Also called IL-2, Proleukin, recombinant human interleukin-2, recombinant interleukin-2

    Given SC

  • laboratory biomarker analysisOther

    Correlative studies

  • flow cytometryOther

    Correlative studies

Study groups in NCT00052598
Study groupRoleWhat they receive
Treatment (adoptive immunotherapy)ExperimentalPatients receive allogeneic CD8+ PR3-specific CTLs IV over 1-2 hours on days 0, 7, 14, 28, and 49 and aldesleukin SC twice daily on days 28-41 and 49-63 in the absence of unacceptable toxicity.
Receives: Biological: therapeutic allogeneic lymphocytes; Biological: aldesleukin; Other: laboratory biomarker analysis; Other: flow cytometry

What is being measured

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

  1. Toxicity rate associated with infusing donor CD8+CTL clones specific for PR3

    Measured: From the first CTL infusion to 4 weeks after the final dose of CTL or IL-2

Secondary outcomes (3)

  1. In vivo persistence of transferred T-cells and assessment of migration to the bone marrow

    Measured: Baseline and days +7, +11, +14, +21, and +28 after each CTL infusion

  2. Duration of response as assessed by PCR or cytogenetic analysis of peripheral blood and bone marrow samples

    Measured: Days +0, +15, +29, +50, +63, and at approximately 1 month after completion of all therapy

  3. Proportion of responders

    Measured: Approximately one month after completion of all therapy

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2003 (estimated)
  2. Study startSep 2002
  3. Primary completionNov 2009
  4. Study completionJun 2011

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
7 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00052598
Sponsor's protocol ID
1671.00
Other IDs
NCI-2010-00826, P01CA018029
Status last verified
Feb 2017
First submitted
24 Jan 2003
Last updated
15 Feb 2017
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing therapeutic allogeneic lymphocytes, aldesleukin and laboratory biomarker analysis in people with Accelerated Phase Chronic Myelogenous Leukemia and Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome, 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 16 inclusion and 7 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 15 Feb 2017. 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?

The study was stopped early. Results are not available in the source record.

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?

Toxicity rate associated with infusing donor CD8+CTL clones specific for PR3 (time frame: From the first CTL infusion to 4 weeks after the final dose of CTL or IL-2). 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 NCT00052598.

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 15 Feb 2017.

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