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CompletedNCT00439465Updated Mar 26, 2019Results posted

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

A Phase 2 interventional study of Ex-vivo expanded effector cells in Myeloma and Transplant-eligible Patients, sponsored by Dartmouth-Hitchcock Medical Center. Completed at 1 site in United States. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2019-03-26.

Sponsored by Dartmouth-Hitchcock Medical Center · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
23
Allocation
Not applicable
Ages
18 Years to 75 Years
Sex
All
01

Study 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 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.

02

Conditions studied

  • Myeloma
  • Transplant-eligible Patients
03

In context

Multiple Myeloma

3,632 studies on the registry are indexed under Multiple Myeloma; 745 are open to participants now.

This study's enrollment of 23 is below the median of 41 across 2,907 interventional studies indexed under Multiple Myeloma.

Browse Multiple Myeloma studies →

Lead sponsor

Dartmouth-Hitchcock Medical Center is the lead sponsor of 472 studies on the registry; 68 are open to participants now.

Of its 30 completed or terminated interventional studies of FDA-regulated products, 20 (67%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

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.
    • 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

Exclusion criteria

Exclusion Criteria:

  • 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
  • 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)
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
23 participants (actual)

Study arms

  • Other
    Ex-vivo expanded effector cells

    Infusing IL-2 and GM-CSF post-Hematopoietic Stem Cell Transplant (HSCT)

    Biological: Ex-vivo expanded effector cells

Interventions

  • BiologicalEx-vivo expanded effector cells

    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.

06

What researchers measure

Primary outcomes

  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).

    Time frame: From initiation of treatment on protocol until Day 100

Secondary outcomes

  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:

    Time frame: 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.

    Time frame: 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.

    Time frame: 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.

    Time frame: 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.

    Time frame: 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.

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

07

Results

Posted Mar 26, 2019

Participant flow

Participant flow — Overall Study
MilestoneEx-vivo Expanded Effector Cells
Started23
Completed19
Not completed4

Outcome measures

PrimaryNumber 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).

Time frame:
From initiation of treatment on protocol until Day 100
Reported as:
Count of participants · Participants
Number of Participants With Adverse Events in All Subjects
ParticipantsEx-vivo Expanded Effector Cells
Number of Participants With Adverse Events in All Subjects11
SecondaryCount 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:

Time frame:
Day 15 post-transplant and between days 21 to 28 post-transplant
Reported as:
Count of participants · Participants
Count of Participants With Increased CD3+CD8+, CD8+ and CD56+ Concentrations Between Day 15 Post-Transplant and Days 21 to 28 Post-transplant
ParticipantsEx-vivo Expanded Effector Cells
Day 15 — Increase7
Day 15 — No Increase9
Days 21-28 — Increase7
Days 21-28 — No Increase9
SecondaryTime 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.

Time frame:
From initiation of treatment on protocol until Day 100
Reported as:
Median · Days
Time to Recovery of Absolute Neutrophil Count
DaysEx-vivo Expanded Effector Cells
Time to Recovery of Absolute Neutrophil Count13 (12 to 16)
SecondaryTime 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.

Time frame:
From initiation of treatment on protocol until Day 100
Reported as:
Median · days
Time to Recovery of Platelet Count
daysEx-vivo Expanded Effector Cells
Time to Recovery of Platelet Count16 (10 to 26)
SecondaryAssessment 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.

Time frame:
From initiation of treatment on protocol until Day 100
Reported as:
Count of participants · Participants
Assessment of Disease Response to Treatment
ParticipantsEx-vivo Expanded Effector Cells
Complete Response12
Very Good Partial Response5
Partial Response1
Progressive disease1
SecondaryNumber 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.

Time frame:
Pre-transplant and following the third and fourth cellular infusions
Reported as:
Count of participants · Participants
Number of Participants With Increased Expression of DAP10 and NKG2D on the CD8 Cell Population
ParticipantsEx-vivo Expanded Effector Cells
Increased abs. NKG2D+CD3+CD8 Tcells12
Increased abs. NKG2D+CD3-CD56+ T cells12
SecondaryDetermine 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.

Time frame:
Pre-transplant and following the third and fourth cellular infusions.
Reported as:
Count of participants · Participants
Determine the Methods of Tumor Cell Killing of the in Vivo CD8+ Cells: Cytotoxicity Assays, Blocking Experiments, Analysis of T-cell Receptor (TCR)
ParticipantsEx-vivo Expanded Effector Cells
Autologous Myeloma Cells — Increased tumor lysis4
Autologous Myeloma Cells — Failure of tumor lysis0
Peripheral blood mononuclear cells — Increased tumor lysis5
Peripheral blood mononuclear cells — Failure of tumor lysis0

Adverse events

Collected over Adverse event data were collected from the start of treatment until 100 days post-treatment for all subjects. Total time of adverse event collection for the study was January 2007 through March 2010. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Ex-vivo Expanded Effector Cells0/23 (0%)0/23 (0%)11/23 (47.8%)
Most frequent other events
Showing 10 of 11
Most frequent other events
EventEx-vivo Expanded Effector Cells
Moderate infectionInfections and infestations3/23
anorexiaMetabolism and nutrition disorders3/23
NauseaGastrointestinal disorders2/23
VomitingGastrointestinal disorders2/23
Increased liver function testsHepatobiliary disorders2/23
FeverGeneral disorders2/23
TachycardiaCardiac disorders2/23
HypotensionCardiac disorders2/23
Severe infectionInfections and infestations1/23
Mucositis - oralGastrointestinal disorders1/23

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Ex-vivo Expanded Effector Cells
<=18 years0
Between 18 and 65 years17
>=65 years6
Age, Continuous
Age, Continuous(Years)Ex-vivo Expanded Effector Cells
Median60 (42 to 72)
Sex: Female, Male
Sex: Female, Male(Participants)Ex-vivo Expanded Effector Cells
Female9
Male14
Race and Ethnicity Not Collected
Race and Ethnicity Not Collected(Participants)Ex-vivo Expanded Effector Cells
Region of Enrollment
Region of Enrollment(Participants)Ex-vivo Expanded Effector Cells
United States23
08

Study locations

1 site
  • Dartmouth-Hitchcock Medical Center
    Lebanon, New Hampshire 03756, United States
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 26, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT00439465
Lead sponsor
Dartmouth-Hitchcock Medical Center
Collaborators
The Leukemia and Lymphoma Society
Responsible party
Kenneth Meehan (Director, Bone Marrow Transplant Program, Dartmouth-Hitchcock Medical Center) — Principal investigator
First posted
Feb 23, 2007
Start date
Jan 2007
Primary completion
Oct 15, 2012
Completion
Nov 30, 2012
Results posted
Mar 26, 2019
Last update
Mar 26, 2019

Study contacts

Kenneth Meehan, MD
principal investigator · Dartmouth-Hitchcock Medical Center

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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