Ewing's SarcomaPhase 2NCT00001566
A Pilot Study of Autologous T-Cell Transplantation With Vaccine Driven Expansion of Anti-Tumor Effectors After Cytoreductive Therapy in Metastatic Pediatric Sarcomas
A Phase 2 study testing therapeutic autologous dendritic cells, indinavir sulfate and peripheral blood stem cell transplantation in people with Ewing's Sarcoma and Rhabdomyosarcoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This is a single arm study. The tumor specimen is analyzed for the presence of a fusion protein which corresponds to available peptides. Patients undergo T cell harvest 10 days after an initial priming peptide-pulsed antigen presenting cell (APC) vaccine is performed. Read more about this study
- Who is it for?
- Ages 5 to 35 years
- Conditions the study is for
- Ewing's Sarcoma, Rhabdomyosarcoma
- What is being tested?
- therapeutic autologous dendritic cells, indinavir sulfate and peripheral blood stem cell transplantation
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 1996to Sep 2008
- 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 5 to 35 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients with fusion protein bearing, metastatic malignancies of the following histologic subtypes are eligible for evaluation for treatment on this protocol: alveolar rhabdomyosarcoma (AR), and Ewing's sarcoma family of tumors (ESFT) which includes classical, atypical and extraosseous Ewing's sarcoma, peripheral primitive neuroectodermal tumors, peripheral neuroepithelioma, primitive sarcoma of bone, and ectomesenchymoma. Eligibility will not be confirmed until the presence of a tumor-specific fusion protein is documented by reverse transcription polymerase chain reaction (RT-PCR) which corresponds to one of the tumor-specific peptides available for vaccination.
- Patients with Stage IV or metastatic disease are eligible to be enrolled on study at the time of initial presentation with tumor, prior to any cytoreductive therapy.
- Alternatively, patients who have recurrent disease, but who have been remotely treated (completed all antineoplastic therapy greater than or equal to one year prior to enrollment for patients who are greater than 5 years of age, or completed all antineoplastic therapy greater than 6 months prior to enrollment for patients who are less than or equal to 5 years of age), are also eligible for enrollment prior to any subsequent cytoreductive therapy.
- Patients who have received cytoreductive therapy for Stage IV or metastatic disease may be enrolled at the time of completion of cytoreductive therapy if an apheresis specimen is available which was collected and processed prior to cytotoxic therapy according to the guidelines described in the protocol Section 3.2.2.
- Such products will have been obtained by apheresis at the Clinical Center, National Institutes of Health (NIH), with informed consent administered as per protocol 98-C-37, 97-C-0050 or as described on standard government request form 2626 for invasive procedures.
- Patients must be less than or equal to 35 years at the time of initial diagnosis of alveolar rhabdomyosarcoma or ESFT, weight greater than 10 kg at the time of apheresis. Patients between 10-15 kg must be approved by the apheresis unit in the Department of Transfusion Medicine (DTM) prior to enrollment on the protocol.
Show all 9Show fewer
- All patients or their legal guardians must give written informed consent indicating their understanding of the investigational nature and risks of the study.
- Patients must have adequate renal function (serum creatinine (Cr) less than 1.5 mg/dl or creatinine clearance (Cr Cl), greater than 60 ml/min./1.73 m^2 and liver function (transaminases less than 3 times normal, bilirubin less than 2.0 mg/dl). Patients will not be excluded based upon abnormal hepatic function which is related to hepatic involvement by tumor.
- For remotely treated patients, a CD4 count of greater than or equal to 400 cells/mm^3 is required.
Who cannot join
- Women who are pregnant or lactating.
- Patients with human immunodeficiency virus infection due to confounding effects on immune function.
- Patients with hepatitis B or hepatitis C infection will be excluded due to the untoward risks to personnel working with blood specimens.
- Patients who require daily oral corticosteroid therapy for any underlying disease will be excluded.
- Topical or inhaled corticosteroids are permitted.
- Patients who are allergic to eggs, egg products, or thimerosal, or have a history of Guillain-Barre syndrome may be enrolled on study but are ineligible to receive the influenza vaccine.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
This is a single arm study.
The tumor specimen is analyzed for the presence of a fusion protein which corresponds to available peptides. Patients undergo T cell harvest 10 days after an initial priming peptide-pulsed antigen presenting cell (APC) vaccine is performed.
Read more
Fresh APCs are utilized for initial priming vaccination. All subsequent vaccinations will use cryopreserved APCs. Minimum number of APCs administered per vaccination is 100,000/kg and maximum is 100,000,000/kg.
Patients undergo cytoreductive therapy for the treatment of their particular malignancy. This therapy usually consists of multiagent chemotherapy in the context of a separate protocol.
Following chemotherapy, infusion of harvested T cells followed by infusion of peptide-pulsed APC vaccinations occurs every 6 weeks for a total of 3 post-priming vaccinations. Influenza vaccine is administered by intramuscular injection concurrent to peptide-pulsed APC vaccines.
Interleukin -2 (IL-2) is administered as a continuous intravenous (IV) infusion for 4 days/week for 3 successive weeks starting on the same day as T cell /peptide-pulsed infusions.
Read the detailed description
Eradication of low tumor burdens can occur in vivo when T-cell mediated responses are generated against specific tumor antigens. The Ewing's sarcoma family of tumors (ESFT) and alveolar rhabdomyosarcoma (AR) display several features which make them candidate diseases for trials of such immunotherapy. First, intensive cytotoxic chemotherapy is generally able to eradicate bulk disease in patients with metastatic disease, but tumor relapse eventually occurs in nearly all patients. Second, tumor-specific chromosomal translocations resulting in the production of novel fusion proteins have been identified in the great majority of these tumors. Peptides derived from these fusion proteins have been shown to function as tumor antigens for cytolytic T cells in animal studies. Third, studies of immune reconstitution after intensive cytotoxic therapy have provided evidence that antigen-specific T cells can be generated in vivo when the adoptive transfer of peripheral T cells and antigen are provided during the period of T cell regeneration. This process can be augmented in murine models by the use of human immunodeficiency virus (HIV) active protease inhibitor, indinavir, potentially through inhibition of programmed cell death in expanding T cells. Merging these concepts, this protocol will attempt to eradicate minimal residual disease in pediatric patients with metastatic ESFT and AR via vaccination with tumor-specific peptides undertaken concomitant with autologous T cell transplantation and indinavir.
- Conditions
- Ewing's Sarcoma, Rhabdomyosarcoma
- Being tested
- therapeutic autologous dendritic cells, indinavir sulfate, peripheral blood stem cell transplantation
- Keywords
- Rhabdomyosarcoma, Ewing's Sarcoma, Immunotherapy, Tumor Vaccine, Interleukin-2
- Medical subject headings
- Sarcoma, Ewing, Rhabdomyosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
therapeutic autologous dendritic cellsBiological
3 syringes containing 1 x 10^6peptide pulsed dendritic cells
indinavir sulfateDrug
Also called Crixivan
Oral dose, 350 mg/m^2 administered every 8 hours. Maximum dose is 800 mg every 8 hours.
peripheral blood stem cell transplantationProcedure or surgery
Harvested autologous T cells, minimum dose 1 x 10^6/kg will be thawed rapidly in 37 degree water bath and infused sequentially over 5-15 minutes.
| Study group | Role | What they receive |
|---|---|---|
| Peptide vaccine/autologous T cell transplant/indinavir therapy | Experimental | Patients receive oral indinavir sulfate 350 mg/m^2 administered every 8 hours; maximum dose i.e. 800 mg every 8 hours; peptide pulsed dendritic cells 1 x 10^6 injection; harvested autologous T cells (minimum dose 1 x 10^6/kg will be thawed rapidly in 37 degree water bath and infused sequentially over 5-15 minutes. Receives: Biological: therapeutic autologous dendritic cells; Drug: indinavir sulfate; Procedure: peripheral blood stem cell transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With an Immune Response to Tumor-specific and Non-tumor Specific Peptides During a Period of Immune Reconstitution
Immune response was defined as a percent specific lysis of >10% following challenge with peptide pulsed targets, or interferon gamma production following challenge with peptide pulsed targets >2-fold that found with no-peptide controls or a proliferation index >3.0. Tumor specific peptides: Ewings sarcoma Type 1: EF-1 (EWS/FLI-1)*SSSYGQQN/PSYDSVRRGA,Ewing's Sarcoma Type 2: EF-2 (EWS/FLI-2)* SSSYGQ/QSSLLAYNT, Alveolar rhabdomyosarcoma: PXFK (PAX3/FKHR)† TIGNGLSPQ/NSIRHNLSL. Non-tumor specific peptide:HPV16E7 MLDLQPETT-MET-9-THR. See protocol link module for additional information re: peptides.
Measured: 20 weeks post vaccination
The Percent of Patients Who Recover CD4 Counts Within 6 Months of Completion of Chemotherapy
CD4 counts were measured from peripheral blood using standard flow cytometric techniques at the following timepoints: 2 months post-chemotherapy, 4 months post-chemotherapy and 6 months post-chemotherapy. To be eligible for evaluation for this endpoint, patient much have been <10 years of age and sustained a CD4 count of <300 cells/mcl upon completion of standard therapy. Recovery was defined as a CD4 count > 500 cells/mcl at any timepoint within 6 months of completing chemotherapy.
Measured: 2 to 6 months
Number of Participants With an Immune Response to the Translocation Breakpoint Peptide
Immune responses were measured following 3 sequential influenza vaccines during the same period as the peptide-pulsed dendritic cell vaccines.
Measured: 5 years
Number of Participants With an Immune Response to Non-Tumor-specific Peptide E7
Immune response was defined as a percent specific lysis of >10% following challenge with peptide pulsed targets, or interferon gamma production following challenge with peptide pulsed targets >2-fold that found with no-peptide controls or a proliferation index >3.0.
Measured: 5 years
Number of Participants With an Immune Response to Tumor-Specific Peptides at the Time of Presentation
Immune response was defined as a percent specific lysis of >10% following challenge with tumor peptide pulsed targets, or interferon gamma production following challenge with tumor peptide pulsed targets >2-fold that found with no-peptide controls or a proliferation index >3.0 to tumor peptide targets.Tumor specific peptides: Ewings sarcoma Type 1: EF-1 (EWS/FLI-1)*SSSYGQQN/PSYDSVRRGA,Ewing's Sarcoma Type 2: EF-2 (EWS/FLI-2)* SSSYGQ/QSSLLAYNT, Alveolar rhabdomyosarcoma: PXFK (PAX3/FKHR)† TIGNGLSPQ/NSIRHNLSL. See protocol link module for additional information re: peptides.
Measured: Once per enrollment
Secondary outcomes (4)
Percentage of Participants Overall Survival
Overall survival is defined as the time between the first day of treatment to the day of death.
Measured: 5 years
Percent of Participants: Event Free Survival
Event free survival is calculated from the date of diagnosis for patients enrolled with newly diagnosed metastatic disease and from the date of the last recurrence detection before enrollment on this study for patients with recurrent disease.
Measured: 5 years
Number of Participants With Adverse Events
Here are the number of participants with adverse events. For the detailed list of adverse events see the adverse event module.
Measured: 5 years
Median Overall Survival
Overall survival is defined as the time between the first day of treatment to the day of death.
Measured: 5.4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 1999 (estimated)
- Study startDec 1996
- Primary completionSep 2008
- Study completionSep 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Ewing's SarcomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Investigators
- Crystal Mackall, M.D., Principal investigator, National Cancer Institute, National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001566
- Sponsor's protocol ID
- 970052
- Other IDs
- 97-C-0052
- Status last verified
- Jun 2012
- First submitted
- 3 Nov 1999
- Last updated
- 15 Jun 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Yanuck M, Carbone DP, Pendleton CD, Tsukui T, Winter SF, Minna JD, Berzofsky JA. A mutant p53 tumor suppressor protein is a target for peptide-induced CD8+ cytotoxic T-cells. Cancer Res. 1993 Jul 15;53(14):3257-61.
PubMed 7686815Mackall CL, Bare CV, Granger LA, Sharrow SO, Titus JA, Gress RE. Thymic-independent T cell regeneration occurs via antigen-driven expansion of peripheral T cells resulting in a repertoire that is limited in diversity and prone to skewing. J Immunol. 1996 Jun 15;156(12):4609-16.
PubMed 8648103Mackall CL, Fleisher TA, Brown MR, Andrich MP, Chen CC, Feuerstein IM, Horowitz ME, Magrath IT, Shad AT, Steinberg SM, et al. Age, thymopoiesis, and CD4+ T-lymphocyte regeneration after intensive chemotherapy. N Engl J Med. 1995 Jan 19;332(3):143-9. doi: 10.1056/NEJM199501193320303.
PubMed 7800006Zhang H, Chua KS, Guimond M, Kapoor V, Brown MV, Fleisher TA, Long LM, Bernstein D, Hill BJ, Douek DC, Berzofsky JA, Carter CS, Read EJ, Helman LJ, Mackall CL. Lymphopenia and interleukin-2 therapy alter homeostasis of CD4+CD25+ regulatory T cells. Nat Med. 2005 Nov;11(11):1238-43. doi: 10.1038/nm1312. Epub 2005 Oct 16.
PubMed 16227988Mackall CL, Rhee EH, Read EJ, Khuu HM, Leitman SF, Bernstein D, Tesso M, Long LM, Grindler D, Merino M, Kopp W, Tsokos M, Berzofsky JA, Helman LJ. A pilot study of consolidative immunotherapy in patients with high-risk pediatric sarcomas. Clin Cancer Res. 2008 Aug 1;14(15):4850-8. doi: 10.1158/1078-0432.CCR-07-4065.
PubMed 18676758
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Autologous T-Cell Transplantation With Vaccine Driven Expansion of Anti-Tumor Effectors After Cytoreductive Therapy in Metastatic Pediatric Sarcomas
- ClinicalTrials.gov ID
- NCT00001566
- Acronym / sponsor ID
- 970052
- Conditions
- Ewing's Sarcoma, Rhabdomyosarcoma
- Keywords
- Rhabdomyosarcoma, Ewing's Sarcoma, Immunotherapy, Tumor Vaccine, Interleukin-2
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Dec 1996
- Primary completion
- Sep 2008 (actual)
- Study completion
- Sep 2008 (actual)
- First posted
- 4 Nov 1999 (estimated)
- Results
- Posted 12 Jun 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single arm study.
The tumor specimen is analyzed for the presence of a fusion protein which corresponds to available peptides. Patients undergo T cell harvest 10 days after an initial priming peptide-pulsed antigen presenting cell (APC) vaccine is performed.
Fresh APCs are utilized for initial priming vaccination. All subsequent vaccinations will use cryopreserved APCs. Minimum number of APCs administered per vaccination is 100,000/kg and maximum is 100,000,000/kg.
Patients undergo cytoreductive therapy for the treatment of their particular malignancy. This therapy usually consists of multiagent chemotherapy in the context of a separate protocol.
Following chemotherapy, infusion of harvested T cells followed by infusion of peptide-pulsed APC vaccinations occurs every 6 weeks for a total of 3 post-priming vaccinations. Influenza vaccine is administered by intramuscular injection concurrent to peptide-pulsed APC vaccines.
Interleukin -2 (IL-2) is administered as a continuous intravenous (IV) infusion for 4 days/week for 3 successive weeks starting on the same day as T cell /peptide-pulsed infusions.
Detailed description
Eradication of low tumor burdens can occur in vivo when T-cell mediated responses are generated against specific tumor antigens. The Ewing's sarcoma family of tumors (ESFT) and alveolar rhabdomyosarcoma (AR) display several features which make them candidate diseases for trials of such immunotherapy. First, intensive cytotoxic chemotherapy is generally able to eradicate bulk disease in patients with metastatic disease, but tumor relapse eventually occurs in nearly all patients. Second, tumor-specific chromosomal translocations resulting in the production of novel fusion proteins have been identified in the great majority of these tumors. Peptides derived from these fusion proteins have been shown to function as tumor antigens for cytolytic T cells in animal studies. Third, studies of immune reconstitution after intensive cytotoxic therapy have provided evidence that antigen-specific T cells can be generated in vivo when the adoptive transfer of peripheral T cells and antigen are provided during the period of T cell regeneration. This process can be augmented in murine models by the use of human immunodeficiency virus (HIV) active protease inhibitor, indinavir, potentially through inhibition of programmed cell death in expanding T cells. Merging these concepts, this protocol will attempt to eradicate minimal residual disease in pediatric patients with metastatic ESFT and AR via vaccination with tumor-specific peptides undertaken concomitant with autologous T cell transplantation and indinavir.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Peptide vaccine/autologous T cell transplant/indinavir therapy | Experimental | Biological: therapeutic autologous dendritic cells, Drug: indinavir sulfate, Procedure: peripheral blood stem cell transplantationPatients receive oral indinavir sulfate 350 mg/m^2 administered every 8 hours; maximum dose i.e. 800 mg every 8 hours; peptide pulsed dendritic cells 1 x 10^6 injection; harvested autologous T cells (minimum dose 1 x 10^6/kg will be thawed rapidly in 37 degree water bath and infused sequentially over 5-15 minutes. |
Who may qualify
- Ages
- 5 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (9 listed)
- Patients with fusion protein bearing, metastatic malignancies of the following histologic subtypes are eligible for evaluation for treatment on this protocol: alveolar rhabdomyosarcoma (AR), and Ewing's sarcoma family of tumors (ESFT) which includes classical, atypical and extraosseous Ewing's sarcoma, peripheral primitive neuroectodermal tumors, peripheral neuroepithelioma, primitive sarcoma of bone, and ectomesenchymoma. Eligibility will not be confirmed until the presence of a tumor-specific fusion protein is documented by reverse transcription polymerase chain reaction (RT-PCR) which corresponds to one of the tumor-specific peptides available for vaccination.
- Patients with Stage IV or metastatic disease are eligible to be enrolled on study at the time of initial presentation with tumor, prior to any cytoreductive therapy.
- Alternatively, patients who have recurrent disease, but who have been remotely treated (completed all antineoplastic therapy greater than or equal to one year prior to enrollment for patients who are greater than 5 years of age, or completed all antineoplastic therapy greater than 6 months prior to enrollment for patients who are less than or equal to 5 years of age), are also eligible for enrollment prior to any subsequent cytoreductive therapy.
- Patients who have received cytoreductive therapy for Stage IV or metastatic disease may be enrolled at the time of completion of cytoreductive therapy if an apheresis specimen is available which was collected and processed prior to cytotoxic therapy according to the guidelines described in the protocol Section 3.2.2.
- Such products will have been obtained by apheresis at the Clinical Center, National Institutes of Health (NIH), with informed consent administered as per protocol 98-C-37, 97-C-0050 or as described on standard government request form 2626 for invasive procedures.
Key exclusion criteria (6 listed)
- Women who are pregnant or lactating.
- Patients with human immunodeficiency virus infection due to confounding effects on immune function.
- Patients with hepatitis B or hepatitis C infection will be excluded due to the untoward risks to personnel working with blood specimens.
- Patients who require daily oral corticosteroid therapy for any underlying disease will be excluded.
- Topical or inhaled corticosteroids are permitted.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| therapeutic autologous dendritic cells3 syringes containing 1 x 10^6peptide pulsed dendritic cells | Biological | Peptide vaccine/autologous T cell transplant/indinavir therapy |
| indinavir sulfateAlso: CrixivanOral dose, 350 mg/m^2 administered every 8 hours. Maximum dose is 800 mg every 8 hours. | Drug | Peptide vaccine/autologous T cell transplant/indinavir therapy |
| peripheral blood stem cell transplantationHarvested autologous T cells, minimum dose 1 x 10^6/kg will be thawed rapidly in 37 degree water bath and infused sequentially over 5-15 minutes. | Procedure or surgery | Peptide vaccine/autologous T cell transplant/indinavir therapy |
Primary outcome
Number of Participants With an Immune Response to Tumor-specific and Non-tumor Specific Peptides During a Period of Immune Reconstitution
Time frame: 20 weeks post vaccination
Immune response was defined as a percent specific lysis of >10% following challenge with peptide pulsed targets, or interferon gamma production following challenge with peptide pulsed targets >2-fold that found with no-peptide controls or a proliferation index >3.0. Tumor specific peptides: Ewings sarcoma Type 1: EF-1 (EWS/FLI-1)*SSSYGQQN/PSYDSVRRGA,Ewing's Sarcoma Type 2: EF-2 (EWS/FLI-2)* SSSYGQ/QSSLLAYNT, Alveolar rhabdomyosarcoma: PXFK (PAX3/FKHR)† TIGNGLSPQ/NSIRHNLSL. Non-tumor specific peptide:HPV16E7 MLDLQPETT-MET-9-THR. See protocol link module for additional information re: peptides.
The Percent of Patients Who Recover CD4 Counts Within 6 Months of Completion of Chemotherapy
Time frame: 2 to 6 months
CD4 counts were measured from peripheral blood using standard flow cytometric techniques at the following timepoints: 2 months post-chemotherapy, 4 months post-chemotherapy and 6 months post-chemotherapy. To be eligible for evaluation for this endpoint, patient much have been <10 years of age and sustained a CD4 count of <300 cells/mcl upon completion of standard therapy. Recovery was defined as a CD4 count > 500 cells/mcl at any timepoint within 6 months of completing chemotherapy.
Number of Participants With an Immune Response to the Translocation Breakpoint Peptide
Time frame: 5 years
Immune responses were measured following 3 sequential influenza vaccines during the same period as the peptide-pulsed dendritic cell vaccines.
Number of Participants With an Immune Response to Non-Tumor-specific Peptide E7
Time frame: 5 years
Immune response was defined as a percent specific lysis of >10% following challenge with peptide pulsed targets, or interferon gamma production following challenge with peptide pulsed targets >2-fold that found with no-peptide controls or a proliferation index >3.0.
Number of Participants With an Immune Response to Tumor-Specific Peptides at the Time of Presentation
Time frame: Once per enrollment
Immune response was defined as a percent specific lysis of >10% following challenge with tumor peptide pulsed targets, or interferon gamma production following challenge with tumor peptide pulsed targets >2-fold that found with no-peptide controls or a proliferation index >3.0 to tumor peptide targets.Tumor specific peptides: Ewings sarcoma Type 1: EF-1 (EWS/FLI-1)*SSSYGQQN/PSYDSVRRGA,Ewing's Sarcoma Type 2: EF-2 (EWS/FLI-2)* SSSYGQ/QSSLLAYNT, Alveolar rhabdomyosarcoma: PXFK (PAX3/FKHR)† TIGNGLSPQ/NSIRHNLSL. See protocol link module for additional information re: peptides.
4 secondary outcomes
Percentage of Participants Overall Survival
Time frame: 5 years
Percent of Participants: Event Free Survival
Time frame: 5 years
Number of Participants With Adverse Events
Time frame: 5 years
Median Overall Survival
Time frame: 5.4 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 7686815Yanuck M, Carbone DP, Pendleton CD, Tsukui T, Winter SF, Minna JD, Berzofsky JA. A mutant p53 tumor suppressor protein is a target for peptide-induced CD8+ cytotoxic T-cells. Cancer Res. 1993 Jul 15;53(14):3257-61.
- Background: PubMed 8648103Mackall CL, Bare CV, Granger LA, Sharrow SO, Titus JA, Gress RE. Thymic-independent T cell regeneration occurs via antigen-driven expansion of peripheral T cells resulting in a repertoire that is limited in diversity and prone to skewing. J Immunol. 1996 Jun 15;156(12):4609-16.
- Background: PubMed 7800006Mackall CL, Fleisher TA, Brown MR, Andrich MP, Chen CC, Feuerstein IM, Horowitz ME, Magrath IT, Shad AT, Steinberg SM, et al. Age, thymopoiesis, and CD4+ T-lymphocyte regeneration after intensive chemotherapy. N Engl J Med. 1995 Jan 19;332(3):143-9. doi: 10.1056/NEJM199501193320303.
- Background: PubMed 16227988Zhang H, Chua KS, Guimond M, Kapoor V, Brown MV, Fleisher TA, Long LM, Bernstein D, Hill BJ, Douek DC, Berzofsky JA, Carter CS, Read EJ, Helman LJ, Mackall CL. Lymphopenia and interleukin-2 therapy alter homeostasis of CD4+CD25+ regulatory T cells. Nat Med. 2005 Nov;11(11):1238-43. doi: 10.1038/nm1312. Epub 2005 Oct 16.
- Results publication: PubMed 18676758Mackall CL, Rhee EH, Read EJ, Khuu HM, Leitman SF, Bernstein D, Tesso M, Long LM, Grindler D, Merino M, Kopp W, Tsokos M, Berzofsky JA, Helman LJ. A pilot study of consolidative immunotherapy in patients with high-risk pediatric sarcomas. Clin Cancer Res. 2008 Aug 1;14(15):4850-8. doi: 10.1158/1078-0432.CCR-07-4065.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
Related trials for Ewing's Sarcoma
RecruitingPhase 1/2
Study of Lurbinectedin Monotherapy in Pediatric and Young Adult Participants With Relapsed/Refractory Ewing Sarcoma
Refractory Ewing Sarcoma, Relapsed Ewing Sarcoma
Not yet recruitingPhase 1
GD2IL18CART Combined With Bevacizumab for Relapsed and Refractory GD2-positive Solid Tumors
Neuroblastoma (NBL), Ewing Sarcoma
Not yet recruitingPhase 1/2
Combination Immunotherapy Targeting Sarcomas
Sarcoma, Osteoid Sarcoma
RecruitingPhase 1
International Phase I Trial of Dinutuximab Beta With VDC/IE in GD2-Positive Ewing Sarkoma
High-risk GD2 Positive Ewing Sarkoma
Not yet recruitingPhase 1/2
Safety and Efficacy Evaluation of 4th Generation Safety-engineered CAR T Cells Targeting Sarcomas
Sarcoma, Osteoid Sarcoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Crystal Mackall, M.D. principal investigator
National Cancer Institute, National Institutes of Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing therapeutic autologous dendritic cells, indinavir sulfate and peripheral blood stem cell transplantation in people with Ewing's Sarcoma and Rhabdomyosarcoma, 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 9 inclusion and 6 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 2012. 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 12 Jun 2012). 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 an Immune Response to Tumor-specific and Non-tumor Specific Peptides During a Period of Immune Reconstitution (time frame: 20 weeks post vaccination). The study lists 5 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 NCT00001566, which also lists 5 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 2012.