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Adult Acute Myeloid Leukemia With 11q23 (MLL) AbnormalitiesPhase 1/2NCT00052520

Biological Therapy in Treating Patients With Advanced Myelodysplastic Syndrome, Acute or Chronic Myeloid Leukemia, or Acute Lymphoblastic Leukemia Who Are Undergoing Stem Cell Transplantation

A Phase 1/2 study testing therapeutic allogeneic lymphocytes, aldesleukin and peripheral blood stem cell transplantation in people with Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities and Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), run by Fred Hutchinson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase I/II trial is studying the side effects of biological therapy and to see how well it works in treating patients with advanced myelodysplastic syndrome, chronic myeloid leukemia, acute myeloid leukemia, or acute lymphoblastic leukemia. Read more about this study

Who is it for?
Any age
What is being tested?
therapeutic allogeneic lymphocytes, aldesleukin and peripheral blood stem cell transplantation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
37 participants
Where
1 siteUnited States
Study dates
Sep 2002to Jun 2013
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

  • Eligibility for Enrollment:
  • a.
  • i) Pre-transplant: Patients undergoing allogeneic hematopoietic stem cell transplantation for refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEB-t), CML beyond chronic phase, AML beyond first remission, Philadelphia chromosome (BCR-ABL)-positive ALL at any stage, any ALL beyond first remission, primary refractory AML or ALL, 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);
  • ii) Post-transplant: Patients who have relapsed after transplant (morphologic, flow cytometric, cytogenetic and molecular relapse) can be offered enrollment on the protocol and may undergo therapy if it is considered possible to control their disease while waiting for the generation of study therapy
  • b. Patients and donors must both express an human leukocyte antigen (HLA)-allele for which it is possible to generate WT1-specific clones for
  • c. Patients must be able to provide blood and bone marrow samples required for this protocol
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  • Eligibility for Prophylactic Treatment with CD8+ CTL After Transplant (Highest Risk Subgroup): At time of planned treatment, CD8+ CTL specific for WT1 must have been generated and have completed Quality Control (QC) testing
  • a. Patients must have had > 5% morphologic blasts detectable in bone marrow or peripheral blood just prior to or at the time of transplant
  • b. Patients must have evidence of post transplant recovery of normal hematopoiesis (absolute neutrophil count [ANC] > 500/mm^3) for at least 7 days prior to the initiation of CTL infusions
  • c. 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 WT1 must have been generated and have completed Quality Control (QC) testing
  • a. Patients must have evidence of recurrent disease post transplant; this includes patients with the following:
  • i) 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
  • ii) 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
  • iii) Cytogenetic relapse 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
  • iv) Molecular relapse defined as: one or more positive polymerase chain reaction (PCR) assays for the presence of clonotypic immunoglobulin heavy chain (IgH) or T cell receptor (TCR) gene rearrangement in patients transplanted for B-or T-cell acute lymphoblastic leukemia, respectively; one or more positive post transplant reverse transcription (RT)-PCR assays for the presence of BCR-ABL messenger ribonucleic acid (mRNA) fusion transcripts in patients transplanted for Philadelphia chromosome (BCRABL)-positive acute lymphoblastic leukemia; (for CML) a PCR assay of bone marrow (BM) or peripheral blood mononuclear cell (PBMC) positive for the presence of the BCR/ABL mRNA fusion transcript that quantitatively increases by greater than one order of magnitude on a subsequent sample
  • b. 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 patients treating physician and the principal investigator
  • DONOR: Both the patient and donor must have an HLA-allele which it is possible to generate WT1-specific clones for
  • DONOR: If a separate leukapheresis via peripheral intravenous access can be arranged, the stem cell donor will undergo leukapheresis to provide the required PBMC no sooner than 2 weeks before or after the stem cell mobilization and harvest
  • DONOR: If a separate leukapheresis is not possible, a portion of the PBMC from the donor's peripheral blood stem cell harvest may potentially be used to generate WT1-specific CTL clones; the feasibility of this option will depend upon the minimal cell dose required for transplantation and the presence of an excess harvest yield and the possibility of generating CTL from this product
  • DONOR: Some donors will be asked to provide both a separate leukapheresis and a portion of the peripheral blood mononuclear cells (PBMC) from the donor's peripheral blood stem cell harvest
  • DONOR: Leukapheresis donors must be age 18 or older

Who cannot join

  • Patients for whom CD8+ CTL clones specific for WT1 have not been generated in time for planned infusion (these patients can potentially be treated later if CTL become available); Also we will exclude patients whose malignant cells do not over express WT-1, 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 MMF is not strictly an exclusion criteria, 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
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  • DONOR: Medical conditions precluding either leukapheresis or blood donation may include but are not limited to:
  • Inadequate age or weight (leukapheresis donors must be age 18 or older, other criteria per physician discretion)
  • Active infection, with or without antibiotic treatment
  • Recent hepatitis exposure, hepatitis A or B antigenemia, or hepatitis C antibody positivity
  • Pregnancy or nursing; HIV or human T-lymphotropic virus (HTLV) infection
  • Severe cardiovascular disease (e.g., uncontrolled hypertension, recent myocardial infarction [MI], or unstable angina)

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+ WT1-Specific CTL Clones for Patients With Advanced MDS, CML, AML or ALL After Allogeneic Hematopoietic Stem Cell Transplant

This phase I/II trial is studying the side effects of biological therapy and to see how well it works in treating patients with advanced myelodysplastic syndrome, chronic myeloid leukemia, acute myeloid leukemia, or acute lymphoblastic leukemia. Biological therapies, including immunotherapy, can potentially be used to stimulate the immune system and stop cancer cells from growing. Immunotherapy given to patients who have undergone donor stem cell transplantation may be a way to eradicate remaining cancer cells

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the safety and potential toxicities associated with infusing donor CD8+ cytotoxic T lymphocyte (CTL) clones specific for Wilms' tumor (WT1) in patients who have relapsed or at a high risk of relapse post transplant for myelodysplastic syndromes (MDS), chronic myelogenous leukemia (CML), acute myeloid leukemia (AML), or acute lymphoblastic leukemia (ALL).

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 WT1-specific T cells mediate antileukemic activity.

OUTLINE: Donors undergo leukapheresis for stem cell harvest to generate CD8-positive WT1 gene-specific CTL clones at the time of allogeneic stem cell transplantation.

After post-transplantation hematopoietic recovery, patients receive treatment for either highest-risk disease (prophylactically) or relapsed disease.

Highest-risk disease group: Patients receive CD8-positive WT1 gene-specific CTL clones intravenously (IV) over 1-2 hours on days 0, 14, and 28. Beginning 2-4 hours after CTL infusion, patients receive interleukin-2 subcutaneously (SC) twice daily on days 28-42 in the absence of unacceptable toxicity.

Relapsed-disease group: Some patients with evidence of leukemic relapse may receive standard salvage chemotherapy prior to donor CTL infusions and then receive CD8-positive WT1 gene-specific CTL clones and interleukin-2 as in the highest-risk group.

Patients in both groups who have progressive disease after complete or partial response to therapy may be eligible for retreatment with CD8-positive WT1 gene-specific CTL clones.

After completion of study treatment, patients are followed every 3 months for 2 years.

Being tested
therapeutic allogeneic lymphocytes, aldesleukin, peripheral blood stem cell transplantation, allogeneic bone marrow transplantation, laboratory biomarker analysis
Medical subject headings
Congenital Abnormalities, Leukemia, Myelomonocytic, Chronic, Thrombocythemia, Essential, Polycythemia Vera, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Anemia, Refractory, with Excess of Blasts

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

  • peripheral blood stem cell transplantationProcedure or surgery

    Also called PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell

    Undergo transplantation

  • allogeneic bone marrow transplantationProcedure or surgery

    Also called bone marrow therapy, allogeneic, bone marrow therapy, allogenic, transplantation, allogeneic bone marrow, transplantation, allogenic bone marrow

    Undergo transplantation

  • laboratory biomarker analysisOther

    Correlative studies

  • gene expression analysisGenetic

    Correlative studies

  • immunologic techniqueOther

    Also called immunological laboratory methods, laboratory methods, immunological

    Correlative studies

  • flow cytometryOther

    Correlative studies

  • polymerase chain reactionGenetic

    Also called PCR

    Correlative studies

  • cytogenetic analysisGenetic

    Correlative studies

  • staining methodOther

    Also called Staining

    Correlative studies

Study groups in NCT00052520
Study groupRoleWhat they receive
TreatmentExperimentalSee Detailed Description
Receives: Biological: therapeutic allogeneic lymphocytes; Biological: aldesleukin; Procedure: peripheral blood stem cell transplantation; Procedure: allogeneic bone marrow transplantation; Other: laboratory biomarker analysis; Genetic: gene expression analysis; Other: immunologic technique; Other: flow cytometry; Genetic: polymerase chain reaction; Genetic: cytogenetic analysis; Other: staining method

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 WT1 in patients at high risk for post transplant relapse of CML, AML, or ALL

    Assessed by Common Terminology Criteria (CTC) version 3.0.

    Measured: Up to 4 weeks after the final dose of CTL

Secondary outcomes (1)

  1. Relapse of disease

    Patients achieving complete remission with chemotherapy and T cell infusions will be followed to determine the duration of response. The proportion of responders will be estimated with associated confidence intervals. Duration of remission will be summarized using time-to-event methods, which will allow estimates to be made while some patients remain in remission.

    Measured: Up to 2 years

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 completionApr 2011
  4. Study completionJun 2013

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
37 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00052520
Sponsor's protocol ID
1655.00
Other IDs
NCI-2009-01471, P01CA018029
Status last verified
Jul 2013
First submitted
24 Jan 2003
Last updated
29 Mar 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 peripheral blood stem cell transplantation in people with Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities and Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), 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 22 inclusion and 12 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: finished, as of the sponsor's last update on 29 Mar 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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 WT1 in patients at high risk for post transplant relapse of CML, AML, or ALL (time frame: Up to 4 weeks after the final dose of CTL). 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 NCT00052520.

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 29 Mar 2017.

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