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NeuroblastomaPhase 1/2NCT00923351

Therapy to Treat Ewing's Sarcoma, Rhabdomyosarcoma or Neuroblastoma

A Phase 1/2 study testing Tumor Purged/CD25 Depleted Lymphocytes, Tumor Purged/CD25 Depleted Lymphocytes with Tumor Lysate/KLH Pulsed Dendritic Cell Vaccine and rhIL-7 in people with Neuroblastoma and Sarcoma, run by National Cancer Institute (NCI) 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

Background: Pediatric solid tumors (Ewing's sarcoma, rhabdomyosarcoma, and neuroblastoma) are often difficult to cure with standard treatment. Immune therapy using an experimental vaccine made from proteins from the patient's tumor cells may boost the body's immune response against the tumor. Read more about this study

Who is it for?
Ages 19 months to 35 years
Conditions the study is for
Neuroblastoma, Sarcoma, Rhabdomyosarcoma-Embryonal
What is being tested?
Tumor Purged/CD25 Depleted Lymphocytes, Tumor Purged/CD25 Depleted Lymphocytes with Tumor Lysate/KLH Pulsed Dendritic Cell Vaccine and rhIL-7
Could I receive a placebo?
No, everyone receives an active treatment
How many people
44 participants
Where
1 siteUnited States
Study dates
2 Jun 2007to 15 May 2018
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 19 months to 35 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Informed Consent
  • Because significant time will have elapsed between apheresis/tumor biopsy and the initiation of immunotherapy, all patients or their legal guardians (if the patient is less than 18 years old) must sign a second informed consent to document their understanding of the investigational nature and the risks of this study before any protocol related studies are performed (other than the studies which were performed to determine patient eligibility).
  • Time and Recovery from Cytotoxic Therapy
  • At least 3 weeks should have elapsed since the last cycle of cytotoxic therapy or since the last dose of radiation therapy, at least 4 weeks must have elapsed since the patient has received any investigational therapy, and patients should have recovered from toxic side effects of previous therapy to a grade 1 or less, with the exception of the following:
  • Hematological toxicity: recovery to levels required in Section 2.1.1.E.
  • Low electrolyte levels (Such individuals should receive appropriate supplementation).
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  • For patients on anticoagulant therapy or with pre-existing coagulation abnormalities, prothrombin time (PT), partial thromboplastin time (PTT) must return to baseline.
  • Liver function tests must resolve to values required in Section 2.1.1.E.
  • Grade 3 hypoalbuminemia.
  • Alopecia.
  • Sterility.
  • Laboratory Parameters
  • renal function: creatinine clearance greater than 60 mL/min/1.73m^2 or normal age adjusted serum creatinine (less than or equal to 5 yrs. less than or equal to 0.8 mg/ml; 5-10 yrs. less than or equal to 1.0 mg/ml; 10-15 yrs. less than or equal to 1.2 mg/ml; greater than 15 yrs. less than or equal to 1.5 mg/ml).
  • liver function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 2.5 times upper limit of normal (ULN), bilirubin less than 1.5 ULN.
  • hematologic function: absolute neutrophil count (ANC) greater than 750 cells/mcl, platelets greater than 50,000 cells/mcl.
  • Birth Control
  • Subjects of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while they are being treated on this study.

Who cannot join

  • Other conditions
  • Clinically significant unrelated systemic illness, such as serious infections or organ dysfunction, which in the judgment of the Principal or Associate Investigators would compromise the patient's ability to tolerate the investigational agents or are likely to interfere with the study procedures or results.
  • Persistent or progressive cancer following the completion of the standard therapy phase of the trial will not, in and of itself, preclude receipt of immunotherapy. However, patients will not receive immunotherapy if they have an Eastern Cooperative Oncology Group (ECOG) performance status performance status of 3 or 4 or, for children less than or equal to 10 years of age, Lansky less than or equal to 50 (Appendix III). Furthermore, patients will be removed from the trial if they develop requirements for anti-neoplastic therapy (e.g. radiation therapy) for progressive disease during the trial as discussed in protocol.
  • Women who are pregnant or lactating.
  • Patients with human immunodeficiency virus infection, hepatitis B, or hepatitis C infection due to confounding effects on immune function.
  • Patients who require chronic daily oral corticosteroid or other immunosuppressive therapy. Topical or inhaled corticosteroids are permitted. Also, a time limited course of steroids does for an unrelated medical condition (e.g. allergic reaction, poison ivy) will not preclude receipt of immunotherapy provided that two weeks elapse between the last dose of systemic corticosteroids and initiation of immunotherapy.
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  • Patients who are receiving other biologic therapies including cytokines or growth factors not specified by the protocol. Herbal supplements will not result in exclusion but should be noted and reviewed with the principal investigator (PI).
  • Patients with a history of CNS metastases from cancer are not excluded provided that the metastatic CNS disease has been effectively treated and there is no evidence of active CNS disease as evidenced by stable clinical findings and stable radiographic findings for a period of 6 weeks.
  • Excluded from Arm B:
  • Patients with history of autoimmune disease (excluding thyroiditis on chronic thyroid replacement therapy) or active auto-immune disease, due to a risk of exacerbation of autoimmunity with r-hIL7. Patients with a history of B cell malignancy due to a risk for growth with rhIL7 therapy.
  • Corrected QT interval (QTc) prolongation defined as a QTc greater than or equal to 470 ms or a prior history of cardiovascular disease, arrhythmias, or significant electrocardiogram (ECG) abnormalities.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: A Pilot Study of Tumor Vaccination and R-hIL-7 Following Standard Multimodality Therapy in Patients With High Risk Pediatric Solid Tumors

Background:

  • Pediatric solid tumors (Ewing's sarcoma, rhabdomyosarcoma, and neuroblastoma) are often difficult to cure with standard treatment.
  • Immune therapy using an experimental vaccine made from proteins from the patient's tumor cells may boost the body's immune response against the tumor.
  • The effects of chemotherapy on the immune system can potentially make immunotherapy more effective if administered soon after completion of chemotherapy. The addition of recombinant human IL-7 (interleukin 7) (rhIL-7 (recombinant human interleukin 7)) may make the immunotherapy more effective.
Read more

Objectives:

-To determine whether immune therapy given after immune suppression can help the body fight the tumor and to determine the safety of the treatment.

Eligibility:

-Patients with solid tumors, i.e., Ewing's sarcoma, rhabdomyosarcoma or neuroblastoma whose disease has recurred after treatment or spread beyond the original site

Design:

  • Patients undergo tumor biopsy (removal of a piece of tumor tissue) to collect tumor cells for making a vaccine from proteins in the patient's tumor and apheresis (removal of a quantity of white blood cells) to collect white cells for re-building the immune system after immune therapy. Apheresis is repeated three times during immunotherapy (weeks 8, 14 and 20).
  • After receiving standard chemotherapy for their tumor (and an additional course of fludarabine and cyclophosphamide to further suppress immunity if needed) patients receive immune therapy in Cohorts A and B. rhIL-7 is given 48 hours before the vaccine, as an injection under the skin in an extremity that will not be used for the vaccine in patients in Cohort B only. You will be watched closely for 6 hours after the rhIL-7 for any signs of reaction. rhIL-7 will be given before vaccine doses #1, #2, #3, and #4. The vaccine is given at study weeks 2, 4, 6, 8, 10 and 12. Each vaccine is given as a total of six separate rhIL-7 followed by injections: three intradermal (like a (tuberculosis) TB test) on one arm or leg and three subcutaneous (like those for insulin injections for diabetes). on the other arm or leg. An anesthetic cream may be used to minimize the discomfort of injections.
  • Patients' white cells are returned to them by infusion through a vein on the first day of immune therapy.
  • Imaging studies and immune studies are done at weeks 1, 8 and 20 to determine the response to treatment on the tumor and on the immune system.
Read the detailed description

Background:

  • Patients with recurrent or metastatic pediatric solid tumors experience low survival rates, but using current standard therapies, many patients with these diseases are rendered into a state of minimal residual disease associated with lymphopenia.
  • Lymphopenic hosts show augmented immune reactivity, which may be favorable for inducing antitumor immune responses.

Objectives:

  • To determine whether Alpha cluster of differentiation 25 (CD25) and 8H9 depleted autologous lymphocytes plus tumor lysate/keyhole limpet hemocyanin (KLH) pulsed dendritic cell vaccines plus or minus r-hIL7 (CYT107) can induce immune responses to tumor lysate in this patient population rendered lymphopenic by cytotoxic therapy.
  • To assess the safety of administering lymphocytes depleted of cluster of differentiation 4 (CD4) plus CD25plus suppressor T cells plus or minus r-hIL (CYT107 (interleukin 7)) to lymphopenic hosts.

Eligibility:

  • Patients with metastatic or recurrent pediatric solid tumors of the following histologies: Ewing's sarcoma family of tumors, rhabdomyosarcoma or neuroblastoma, synovial cell sarcoma, desmoplastic small round cell tumor, undifferentiated sarcoma, embryonal sarcoma.
  • Patients must have sufficient accessible tumor for biopsy to generate tumor lysate.
  • Patients must meet eligibility criteria upon enrollment and upon completion of standard therapy prior to administration of immunotherapy as significant time will have elapsed between the time points.

Design:

  • Immunotherapy consists of one autologous lymphocyte infusion depleted of CD25plus suppressive T cells and depleted of contaminating tumor cells plus 6 sequential tumor lysate/KLH pulsed dendritic cell vaccines. No cytokine is administered on Arm A and r-hIL7 (CYT107) is administered on Arm B.
  • Patients will be evaluated for immune responses to tumor lysates using ex vivo assays and delayed type hypersensitivity (DTH).
  • The trial uses a one-stage design targeting a response rate of 50 percent. Up to 47 patients will be treated.
  • Stopping rules will take effect if excessive toxicity is observed.
Being tested
Tumor Purged/CD25 Depleted Lymphocytes, Tumor Purged/CD25 Depleted Lymphocytes with Tumor Lysate/KLH Pulsed Dendritic Cell Vaccine, rhIL-7, Tumor Lysate/KLH Pulsed Dendritic Cell Vaccine
Keywords
Vaccine, Immunotherapy, Cancer, Chemotherapy, Tumor Lysate/KLH Pulsed Dendritic Cell Vaccine, Neuroblastoma, Autologous Lymphocyte Infusion, Ewing's Sarcoma, Rhabdomyosarcoma
Medical subject headings
Neuroblastoma, Sarcoma, Rhabdomyosarcoma, Embryonal, Rhabdomyosarcoma, Alveolar, Neuroectodermal Tumors, Primitive, Peripheral, Neoplasms, Sarcoma, Ewing, Rhabdomyosarcoma

What participants receive

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

  • Tumor Purged/CD25 Depleted LymphocytesDrug

  • Tumor Purged/CD25 Depleted Lymphocytes with Tumor Lysate/KLH Pulsed Dendritic Cell VaccineBiological

    Tumor lysate/KLH pulsed dendritic cells (minimum of 1 X 10e6 cells/kg) on Day2.

  • rhIL-7Drug

    rhIL-7 (20 mcg/kg/dose SQ) approx. 48 hours prior to vaccine) Day 0, Day 14, Day 28 and Day 42

  • Tumor Lysate/KLH Pulsed Dendritic Cell VaccineBiological

    Tumor lysate/KLH Pulsed dendritic cell vaccine (1-5 X 10e7 cells/injection site, given in 3 sites intradermal) on Day 2, Day 16, Day 30, Day 44, Day 56, Day 70.

Study groups in NCT00923351
Study groupRoleWhat they receive
Arm A - Participants who did not receive rhIL-7ExperimentalSix patients with Ewings sarcoma family or tumors (ESFT) participants will receive cytotoxic/lympholytic therapy with cyclophosphamide and fludarabine (if cluster of differentiation 4 (CD4) count > 200 cells/mcl). Participant will receive Tumor lysate/keyhole limpet hemocyanin (KLH) pulsed dendritic cell vaccine followed by Infusion of 8H9/CD25 depleted autologous lymphocyte infusion on Day 1, followed by Tumor lysate/KLH pulsed dendritic cell vaccine on week 4, 6, 8, 10, and 12.
Receives: Drug: Tumor Purged/CD25 Depleted Lymphocytes
Arm B - Participants who received rhIL-7ExperimentalEight patients with rhabdomyosarcoma, fifteen patients with Ewings sarcoma family or tumors (ESFT), two patients with desmoplastic small round cell tumor, and one patient with synovial cell sarcoma participants will receive CYT107 20 mcg/kg/dose subcutaneous (SQ) (approx. 48h prior to vaccine[Day 0]), Tumor lysate/KLH pulsed dendritic cell vaccine followed by Infuse 8H9/CD25 depleted autologous lymphocyte infusion on Day 2, followed by CYT107 20 mcg/kg/dose SQ on days 14, 28 and 42 (± 7 days), and Tumor lysate/KLH pulsed dendritic cell vaccine on Days 16, 30, 44, 56, and 70 (± 7 days). Apheresis/flow cytometry/delayed type of hypersensitivity (DTH) responses for immune endpoint monitoring (skin tests) will be performed on Week 8, 14, 20 (Arm A) and on Days 42, 84 and 126 (+/- 7 days) (Arm B); and radiographic studies for clinical restaging will be performed on Week 8 and 20 (Arm A) and Days 42 and 126 (+/- 7 days) (Arm B).
Receives: Biological: Tumor Purged/CD25 Depleted Lymphocytes with Tumor Lysate/KLH Pulsed Dendritic Cell Vaccine; Drug: rhIL-7; Biological: Tumor Lysate/KLH Pulsed Dendritic Cell Vaccine

What is being measured

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

  1. Number of Participants With a Positive Immune Response as Evidenced by the Delayed Type of Hypersensitivity (DTH) Reaction Assay

    A positive response to the tumor vaccine requires a positive reaction in at least one of the two assays below (immune responses to tumor lysates using ex vivo and delayed type of hypersensitivity (DTH).

    The presence of a positive delayed type of hypersensitivity (DTH) reaction to the tumor lysate in a patient who did not show a positive DTH reaction prior to immunotherapy. A positive reaction is induration of at least 0.5 cm.

    Immunotherapy administered to patients with recurrent or metastatic pediatric solid tumors such as Ewing's sarcoma, rhabdomyosarcoma, or neuroblastoma. Each vaccine is given as 6 separate injections. Three intradermal on one arm or leg and three subcutaneous on the other arm or leg.

    Measured: Week 8, 14, 20 (Arm A) and on Days 42, 84 and 126 (± 7 days) (Arm B)

  2. Toxicity

    Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.

    Measured: Date treatment consent signed to date off study, approximately 49.5 months

  3. Overall Survival

    Overall survival is defined as the time between the first day of treatment to the day of death.

    Measured: Time between the first day of treatment to the day of death or at the conclusion of 5 years of follow-up, whichever comes first, assessed up to approximately 11 years.

Timeline

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

  1. First posted18 Jun 2009 (estimated)
  2. Study start2 Jun 2007
  3. Primary completion30 Aug 2012
  4. Study completion15 May 2018

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
44 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00923351
Sponsor's protocol ID
070206
Other IDs
07-C-0206
Status last verified
May 2018
First submitted
17 Jun 2009
Last updated
15 Jun 2018
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Arndt CA, Crist WM. Common musculoskeletal tumors of childhood and adolescence. N Engl J Med. 1999 Jul 29;341(5):342-52. doi: 10.1056/NEJM199907293410507. No abstract available.

    PubMed 10423470

  • La TH, Meyers PA, Wexler LH, Alektiar KM, Healey JH, Laquaglia MP, Boland PJ, Wolden SL. Radiation therapy for Ewing's sarcoma: results from Memorial Sloan-Kettering in the modern era. Int J Radiat Oncol Biol Phys. 2006 Feb 1;64(2):544-50. doi: 10.1016/j.ijrobp.2005.07.299. Epub 2005 Sep 28.

    PubMed 16198063

  • Barker LM, Pendergrass TW, Sanders JE, Hawkins DS. Survival after recurrence of Ewing's sarcoma family of tumors. J Clin Oncol. 2005 Jul 1;23(19):4354-62. doi: 10.1200/JCO.2005.05.105. Epub 2005 Mar 21.

    PubMed 15781881

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Tumor Purged/CD25 Depleted Lymphocytes, Tumor Purged/CD25 Depleted Lymphocytes with Tumor Lysate/KLH Pulsed Dendritic Cell Vaccine and rhIL-7 in people with Neuroblastoma and Sarcoma, run by National Cancer Institute (NCI) 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 17 inclusion and 11 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 15 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 20 Sep 2013). 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 a Positive Immune Response as Evidenced by the Delayed Type of Hypersensitivity (DTH) Reaction Assay (time frame: Week 8, 14, 20 (Arm A) and on Days 42, 84 and 126 (± 7 days) (Arm B)). The study lists 3 primary outcomes in all. 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 NCT00923351, which also lists 3 linked publications.

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 Jun 2018.

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