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MyelomaPhase 2NCT00439465

Adoptive Cellular Immunotherapy Following Autologous Peripheral Blood Stem Cell Transplantation for Multiple Myeloma

A Phase 2 study testing Ex-vivo expanded effector cells in people with Myeloma and Transplant-eligible Patients, run by Dartmouth-Hitchcock Medical 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

The purpose of this study is to determine whether the administration of highly effective "killer" cells (cytotoxic T cells), along with Interleukin-2 (IL-2) and Recombinant Human Granulocyte Colony Stimulating Factor (GM-CSF) immediately following Autologous Peripheral Blood Stem Cell Transplantation (APBSCT) will… Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Myeloma, Transplant-eligible Patients
What is being tested?
Ex-vivo expanded effector cells
Could I receive a placebo?
No, everyone receives an active treatment
How many people
23 participants
Where
1 siteUnited States
Study dates
Jan 2007to 30 Nov 2012
Phase
Phase 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 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Multiple Myeloma:
  • Patients must meet criteria for diagnosis of Multiple Myeloma.
  • Patient must meet either criterion listed below:
  • Stage I, II, or III newly diagnosed multiple myeloma
  • Progressive or relapsed disease in partial response (PR) or complete response (CR)
  • Primary refractory disease.
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  • Relapsed refractory disease.
  • Patients may have received a prior autologous transplant.
  • The patients must have recovered from all serious and life threatening effects of previous treatment at the time of study entry (unless this abnormality is believed to be due to the underlying myeloma).
  • The patient must have adequate bone marrow function, i.e. a total white blood cell count (WBC) of > 2,000/ul, a Hemoglobin (Hgb) of > 7 gm/dl, and a platelet count of > 50,000/ul, unless this abnormality is believed to be due to the underlying myeloma.
  • The patient must have adequate liver function, i.e. bilirubin <2.0 mg/dl, aspartate aminotransferase (SGOT), alanine aminotransferase (SGPT) not greater than 2 times the upper normal limit (unless this abnormality is believed to be due to the underlying myeloma).
  • The patient must have adequate renal function, i.e. serum creatinine < 3.0 mg/dl, and/or creatinine clearance >50 ml/min. This eligibility criterion is excluded if renal insufficiency is believed to be secondary to myeloma.
  • Age >18 years and < 75 years old
  • The patient must have a Karnofsky status > 80%
  • Patients must have a life expectancy of at least 12 weeks
  • Left ventricular ejection fraction of > 45% by radionuclide scan or echocardiography
  • Pulmonary function tests: forced vital capacity, Diffusing capacity of the lungs for carbon monoxide (DLCO) and expiratory volume in one second (FEV1) must be > 50% of predicted
  • No significant co-morbid medical or psychiatric illness which would significantly compromise the patient's clinical care and chances of survival.
  • Informed written consent must be obtained. Patients must be able to give informed consent as a prerequisite to this procedure. The Informed Consent form will become part of his/her permanent record and a copy will be given to the patient

Who cannot join

  • Medical, social, or psychological factors which would prevent the patient from receiving or cooperating with the full course of therapy.
  • Evidence on physical exam, lumbar puncture, computed tomography (CT), or magnetic resonance imaging (MRI) scan of central nervous system (CNS) involvement with malignancy
  • Any clinically significant cardiac disease (angina, myocardial infarction, congestive heart failure, ventricular arrhythmias requiring therapy) or clinically significant obstructive/restrictive pulmonary disease
  • Serology positive for human immunodeficiency virus (HIV) or human T-lymphotropic virus (HTLVI)
  • Active hepatitis B or C
  • History of seizures
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  • Concurrent or expected need for therapy with corticosteroids
  • Active connective tissue disease
  • Current "clinically significant" pleural effusion, pericardial effusion, or ascites
  • Positive pregnancy test or presence of lactation
  • Collection of fewer than 1 x 106 cluster of differentiation 34 positive (CD34+) cells/kg (peripheral blood stem cells). If the apheresis collection is inadequate based on this criteria, the patient will be removed from protocol and a marrow harvest may be performed
  • A history of a second malignancy (other then squamous cell/ basal cell carcinoma of the skin or cervical dysplasia) must be reviewed by the Principal Investigator, before inclusion or exclusion in the study. Based upon the PI's review, this patient may be eligible (i.e., distant past history of a malignancy)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Dartmouth-Hitchcock Medical Center

    Lebanon, New Hampshire, 03756

Other trials in United States

About this study

The purpose of this study is to determine whether the administration of highly effective "killer" cells (cytotoxic T cells), along with Interleukin-2 (IL-2) and Recombinant Human Granulocyte Colony Stimulating Factor (GM-CSF) immediately following Autologous Peripheral Blood Stem Cell Transplantation (APBSCT) will enhance anti-tumor immune reconstitution and improve outcome of Multiple Myeloma patients.

The overall hypothesis of this proposal is that immediately following APBSCT the immune reconstitution is optimal to administer "killer" cells, combined with the administration of IL-2 and GM-CSF.

Being tested
Ex-vivo expanded effector cells
Medical subject headings
Neoplasms, Plasma Cell

What participants receive

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

  • Ex-vivo expanded effector cellsBiological

    This trial will test if the combination of infusing ex vivo expanded cytotoxic effector cells with IL-2 and GM-CSF post-transplant will accelerate immune reconstitution, resulting in an effector cell-versus-myeloma effect and, possibly, improved clinical outcomes.

Study groups in NCT00439465
Study groupRoleWhat they receive
Ex-vivo expanded effector cellsOtherInfusing IL-2 and GM-CSF post-Hematopoietic Stem Cell Transplant (HSCT)
Receives: Biological: Ex-vivo expanded effector cells

What is being measured

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

  1. Number of Participants With Adverse Events in All Subjects

    To establish the safety (toxicity) of myeloma patients treated with high dose melphalan, autologous peripheral blood stem cell transplantation (APBSCT) \& adoptive transfer of cytotoxic effector cells with Interleukin-2 (IL-2) and Recombinant Human Granulocyte Colony Stimulating Factor (GM-CSF).

    Measured: From initiation of treatment on protocol until Day 100

Secondary outcomes (6)

  1. Count of Participants With Increased CD3+CD8+, CD8+ and CD56+ Concentrations Between Day 15 Post-Transplant and Days 21 to 28 Post-transplant

    To demonstrate that the effector cell infusions result in a clinical effect, phenotypic analyses of blood samples using flow cytometry will be performed prior to, and after each infusion, focusing on the CD8 + populations (CD3+CD8+, CD8+CD56+). As a complement to flow cytometry, the following assays will be used to identify cell subset precursor frequencies, subset proliferation, and cytokine production:

    • Dye Dilution Proliferation Assay (DDPA) 36 - Evaluation of CD8+ T Cell Precursors
    • ELISPOT-Quantifying cytokine producing T cells:

    Measured: Day 15 post-transplant and between days 21 to 28 post-transplant

  2. Time to Recovery of Absolute Neutrophil Count

    To establish the time to engraftment of myeloma patients treated with high dose melphalan, APBSCT\& adoptive transfer of cytotoxic effector cells with IL-2 and GM-CSF.

    Measured: From initiation of treatment on protocol until Day 100

  3. Time to Recovery of Platelet Count

    To establish the time to engraftment of myeloma patients treated with high dose melphalan, APBSCT\& adoptive transfer of cytotoxic effector cells with IL-2 and GM-CSF.

    Measured: From initiation of treatment on protocol until Day 100

  4. Assessment of Disease Response to Treatment

    To establish the disease response of myeloma patients treated with high dose melphalan, APBSCT\& adoptive transfer of cytotoxic effector cells with IL-2 and GM-CSF.

    Measured: From initiation of treatment on protocol until Day 100

  5. Number of Participants With Increased Expression of DAP10 and NKG2D on the CD8 Cell Population

    • Isolate CD3+CD8+ and CD8+CD56+ from patients' blood following transplant.
    • Identify NKG2D and DAP10 expression.
    • Determine the mechanism of tumor cell killing and the relationship to NKG2D or DAP 10 expression.

    After isolating CD8+ cells from patient's blood samples using the AutoMACS, we will evaluate the expression of NKG2D and DAP10 on all CD8+ cells (CD3+CD8+ and CD8+CD56+cells) pre-transplant (Baseline) and following the third and fourth cellular infusions using phenotypic analysis. We postulate the increased expression of both DAP10 and NKG2D on the CD8 population immediately following APSCT and effector cell infusions when compared to baseline.

    Measured: Pre-transplant and following the third and fourth cellular infusions

  6. Determine the Methods of Tumor Cell Killing of the in Vivo CD8+ Cells: Cytotoxicity Assays, Blocking Experiments, Analysis of T-cell Receptor (TCR)

    We will isolate the CD8+ populations (CD3+CD8+, CD8+CD56+) using the Auto MACS (Miltenyi) and then identify the mechanisms of tumor cell killing by the CD8+ cells obtained pre-transplant (Baseline) and following the third and fourth cellular infusions. We will examine mechanisms of tumor cell killing through NKG2D receptor, major histocompatibility complex (MHC) Class I molecules or through the T cell receptor. We postulate the CD8+ cells obtained from patient's blood will kill tumor cells both via MHC Class I and through the NKG2D receptor.

    Measured: Pre-transplant and following the third and fourth cellular infusions.

Timeline

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

  1. First posted23 Feb 2007 (estimated)
  2. Study startJan 2007
  3. Primary completion15 Oct 2012
  4. Study completion30 Nov 2012

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
23 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00439465
Sponsor's protocol ID
D0717
Status last verified
Mar 2019
First submitted
21 Feb 2007
Last updated
26 Mar 2019
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ex-vivo expanded effector cells in people with Myeloma and Transplant-eligible Patients, run by Dartmouth-Hitchcock Medical 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 19 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 26 Mar 2019. 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 phase mean?

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 26 Mar 2019). 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?

Number of Participants With Adverse Events in All Subjects (time frame: From initiation of treatment on protocol until Day 100). 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 NCT00439465.

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 26 Mar 2019.

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