Metastatic CancerPhase 1/2NCT00924287
Gene Therapy Using Anti-Her-2 Cells to Treat Metastatic Cancer
A Phase 1/2 study testing in vitro tumor reactive, chimeric T cell receptor (CAR ) gene-transduced PBL plus IV aldesleukin, Cyclophosphamide and Fludarabine in people with Metastatic Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Background: Human epidermal growth factor receptor-2 (Her-2) is a gene found in both normal cells and cancer cells. Extra copies of the gene (overexpression) can cause too many Her-2 proteins (receptors) to appear on the cell surface and cause tumors to grow. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Cancer
- What is being tested?
- in vitro tumor reactive, chimeric T cell receptor (CAR ) gene-transduced PBL plus IV aldesleukin, Cyclophosphamide and Fludarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2008to Dec 2010
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Metastatic cancer that expresses Her-2 at greater than or equal to 2+ and assessed by immunohistochemistry (IHC) in the clinical laboratory improvement amendment (CLIA) approved test in the Laboratory of Pathology, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH).
- Patients must have previously received systemic standard care (or effective salvage chemotherapy regimens) for metastatic disease, if known to be effective for that disease, and have been either non-responders (progressive disease) or have recurred. Subjects with estrogen receptor-positive or progesterone receptor-positive breast cancer must have progressed on or not be a candidate for anti-estrogens or aromatase inhibitors and all breast cancer patients must have progressed on or not be a candidate for an anthracycline-containing regimen and a taxane-containing regimen.
- Patients with breast cancer must have previously received trastuzumab. Patients will not continue to receive trastuzumab during the trial period.
- Greater than or equal to 18 years of age.
- Willing to sign a durable power of attorney
- Able to understand and sign the Informed Consent Document
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- Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1.
- Life expectancy of greater than three months.
- Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for up to four months after receiving the preparative regimen.
- Serology:
- Seronegative for human immunodeficiency virus (HIV) antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune-competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.)
- Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then patient must be tested for the presence of antigen by reverse transcriptase polymerase chain reaction (RT-PCR) and be hepatitis C virus ribonucleic acid (HCV RNA) negative.
- Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the preparative chemotherapy on the fetus.
- Hematology:
- Absolute neutrophil count greater than 1000/mm^3 without the support of filgrastim.
- White blood cell (WBC) (> 3000/mm^3).
- Platelet count greater than 100,000/mm^3.
- Hemoglobin greater than 8.0 g/dl.
- Chemistry:
- Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less or equal to 2.5 times the upper limit of normal.
- Serum creatinine less than or equal to 1.6 mg/dl.
- Total bilirubin less than or equal to 1.5 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.
- Left ventricular ejection fraction (LVEF) greater than or equal to 50%.
- More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patients' toxicities must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo).
- Patients who have previously received anti-cytotoxic T-lymphocyte antigen 4 (CTLA4) antibody therapy must have a normal colonoscopy with normal colonic biopsies.
Who cannot join
- Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
- Active systemic infections; coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system; myocardial infarction; cardiac arrhythmias; obstructive or restrictive pulmonary disease.
- Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
- Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities).
- Concurrent Systemic steroid therapy
- History of severe immediate hypersensitivity reaction to any of the agents used in this study.
Show all 10Show fewer
- History of coronary revascularization or ischemic symptoms
- Documented forced expiratory volume in 1 second (FEV1) less than or equal to 60% predicted tested in patients with:
- A prolonged history of cigarette smoking (20 pack/year of smoking within the past 2 years).
- Symptoms of respiratory dysfunction
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
Official title: Phase I/II Study of Metastatic Cancer That Expresses Her-2 Using Lymphodepleting Conditioning Followed by Infusion of Anti-Her-2 Gene Engineered Lymphocytes
Background:
- Human epidermal growth factor receptor-2 (Her-2) is a gene found in both normal cells and cancer cells. Extra copies of the gene (overexpression) can cause too many Her-2 proteins (receptors) to appear on the cell surface and cause tumors to grow.
- An experimental procedure developed for treating patients with cancer uses blood cells found in their tumors or bloodstream. The cells are genetically modified using the anti-Her-2 gene and a type of virus. The modified cells (anti-Her-2 cells) are grown in the laboratory and then given back to the patient to try to decrease the size of the tumors. This is called gene therapy.
Read more
Objectives:
- To determine whether advanced cancers that overexpress Her-2 can be treated effectively with lymphocytes (white blood cells) that have been genetically engineered to contain an anti-Her-2 protein.
Eligibility:
- Patients 18 years of age and older with metastatic cancer (cancer that has spread beyond the original site) and for whom standard treatments are not effective.
- Patient's tumor overexpresses Her-2.
Design:
- Workup with scans, x-rays and other tests.
- Leukapheresis to obtain cells for preparing the anti-Her-2 cells for later infusion.
- 1 week of chemotherapy to prepare the immune system for receiving the anti-Her-2 cells.
- Infusion of anti-Her-2 cells, followed by interleukin-2 (IL-2) treatment. The cells are given as an infusion through a vein. IL-2 is given as a 15-minute infusion through a vein every 8 hours for a maximum of 15 doses.
- Periodic follow-up clinic visits after hospital discharge for physical examination, review of treatment side effects, laboratory tests and scans every 1 to 6 months.
Read the detailed description
Background:
- We have constructed a single retroviral vector that contains a chimeric T cell receptor (CAR) that recognizes the Her-2 tumor antigen, which can be used to mediate genetic transfer of this CAR with high efficiency (greater than 30%) without the need to perform any selection.
- In co-cultures with Her-2 positive tumors, anti-Her-2 CAR transduced T cells secreted significant amount of interferon-gamma (IFN-gamma) (Her-2 high specificity).
Objectives:
Primary objectives:
- To evaluate the safety of the administration of anti-Her-2 -CAR engineered peripheral blood lymphocytes in patients receiving the non-myeloablative conditioning regimen and aldesleukin.
- Determine if the administration of anti-Her-2 -CAR engineered peripheral blood lymphocytes and aldesleukin to patients following a nonmyeloablative but lymphoid depleting preparative regimen will result in clinical tumor regression in patients with metastatic cancer that expresses the Her-2 antigen.
Secondary objective:
- Determine the in vivo survival of CAR gene-engineered cells.
Eligibility:
Patients who are 18 years of age or older must have
- metastatic cancer whose tumors express the Her-2 antigen;
- previously received and have been a non-responder to or recurred after standard care for metastatic disease;
Patients may not have:
- contraindications for high dose aldesleukin administration.
Design:
- Peripheral blood mononuclear cell (PBMC) obtained by leukapheresis (approximately 5 times 10^9 cells) will be cultured in the presence of anti-CD3 (OKT3) and aldesleukin in order to stimulate T-cell growth.
- Transduction is initiated by exposure of approximately 10^8 to 5 times 10^8 cells to retroviral vector supernatant containing the anti-Her-2 CAR genes .
- Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous (IV) infusion of ex vivo tumor reactive, CAR genetransduced PBMC plus IV aldesleukin (720,000 IU/kg q8h for a maximum of 15 doses).
- Patients will undergo complete evaluation of tumor with physical examination, computed tomography (CT) of the chest, abdomen and pelvis and clinical laboratory evaluation four to six weeks after treatment. If the patient has stable disease (SD) or tumor shrinkage, repeat complete evaluations will be performed every 1-3 months. After the first year, patients continuing to respond will continue to be followed with this evaluation every 3-4 months until off study criteria are met.
- The study will be conducted using a Phase I/II optimal design. The protocol will proceed in a phase 1 dose escalation design, with three cohorts. Should a single patient experience a dose limiting toxicity (DLT) at a particular dose level, three more patients would be treated at that dose to confirm that no greater than 1/6 patients have a DLT prior to proceeding to the next higher level. If a level with 2 or more DLTs in 3-6 patients has been identified, three additional patients will be accrued at the next-lowest dose, for a total of 6, in order to further characterize the safety of the maximum tolerated dose prior to starting the phase II portion. If a dose limiting toxicity occurs in the first cohort, that cohort will be expanded to 6 patients. If 2 DLTs are encountered in this cohort, the study will be terminated.
- Once the maximum tolerated dose (MTD) has been determined, the study then would proceed to the phase II portion. Patients will be entered into two cohorts based on histology: cohort 1 will include patients with metastatic breast cancer, and cohort 2 will include patients with other types of metastatic cancer that express Her-2.
- For each of the 2 strata evaluated, the study will be conducted using a phase II optimal design where initially 21 evaluable patients will be enrolled. For each of these two arms of the trial, if 0 or 1 of the 21 patients experiences a clinical response, then no further patients will be enrolled but if 2 or more of the first 21 evaluable patients enrolled have a clinical response, then accrual will continue until a total of 41 evaluable patients have been enrolled in that stratum.
- The objective will be to determine if the combination of high dose aldesleukin, lymphocyte depleting chemotherapy, and anti-Her-2 CAR-gene engineered lymphocytes is able to be associated with a clinical response rate that can rule out 5% (p0=0.05) in favor of a modest 20% partial response (PR) + complete response (CR) rate (p1=0.20).
- Conditions
- Metastatic Cancer
- Being tested
- in vitro tumor reactive, chimeric T cell receptor (CAR ) gene-transduced PBL plus IV aldesleukin, Cyclophosphamide, Fludarabine, Mesna
- Keywords
- Metastatic Cancer, Tumor Regression, Immunotherapy, Safety, Cancer
- Medical subject headings
- Neoplasm Metastasis, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
in vitro tumor reactive, chimeric T cell receptor (CAR ) gene-transduced PBL plus IV aldesleukinDrug
Also called Proleukin, IL-2, Interleukin-2
720,000 IU/kg every 8 hours for a maximum of 15 doses
CyclophosphamideDrug
Also called Cytoxan, Neosar, Endoxan, Procytox
60 mg/kg/day x 2 days intravenously (IV) in 250 ml 5% dextrose in water (D5W) with mesna 15 mg/kg/day x 2 days over 1 hour
FludarabineDrug
Also called Fludara
25 mg/m^2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days.
MesnaDrug
Also called Mesnex, Uromitexan
3 mg/kg/hour intravenously diluted in a suitable diluent over 23 hours after each cyclophosphamide dose.
| Study group | Role | What they receive |
|---|---|---|
| Metastatic Cancer | Experimental | Cancer that has invaded other parts of the body Receives: Drug: in vitro tumor reactive, chimeric T cell receptor (CAR ) gene-transduced PBL plus IV aldesleukin; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Mesna |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With an Objective Clinical Tumor Regression Response
Response Evaluation Criteria in Solid Tumors (RECIST) are used to determine objective clinical response. Complete Rresponse (CR) is the disappearance of all target lesions, partial response (PR) is at least a 30% decrease in the target lesions, progressive disease (PD) is at least a 20% increase in the target lesions or appearance of one or more new lesions, and stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Measured: 12 days
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: 12 days
Secondary outcomes (1)
Number of Participants With In Vivo Survival of Transfused Cells
In-vivo survival of infused cells is determined by analysis of the sequence of the variable region of the T cell receptor or flow cytometry (FACS).
Measured: 12 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2009 (estimated)
- Study startNov 2008
- Primary completionDec 2010
- Study completionDec 2010
Why it stopped: This study was terminated after the first patient treated on study died as a result of the treatment.
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 (3)Papers the sponsor has linked to this study.
- Other trials for Metastatic CancerStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Steven Rosenberg, M.D., National Institutes of Health Clinical Center (CC)
- Investigators
- Steven A Rosenberg, M.D., Principal investigator, National Cancer Institute, National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00924287
- Sponsor's protocol ID
- 090041
- Other IDs
- 09-C-0041
- Status last verified
- Oct 2015
- First submitted
- 17 Jun 2009
- Last updated
- 28 Oct 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Kawakami Y, Eliyahu S, Sakaguchi K, Robbins PF, Rivoltini L, Yannelli JR, Appella E, Rosenberg SA. Identification of the immunodominant peptides of the MART-1 human melanoma antigen recognized by the majority of HLA-A2-restricted tumor infiltrating lymphocytes. J Exp Med. 1994 Jul 1;180(1):347-52. doi: 10.1084/jem.180.1.347.
PubMed 7516411Dudley ME, Wunderlich J, Nishimura MI, Yu D, Yang JC, Topalian SL, Schwartzentruber DJ, Hwu P, Marincola FM, Sherry R, Leitman SF, Rosenberg SA. Adoptive transfer of cloned melanoma-reactive T lymphocytes for the treatment of patients with metastatic melanoma. J Immunother. 2001 Jul-Aug;24(4):363-73. doi: 10.1097/00002371-200107000-00012.
PubMed 11565838Dudley ME, Wunderlich JR, Yang JC, Hwu P, Schwartzentruber DJ, Topalian SL, Sherry RM, Marincola FM, Leitman SF, Seipp CA, Rogers-Freezer L, Morton KE, Nahvi A, Mavroukakis SA, White DE, Rosenberg SA. A phase I study of nonmyeloablative chemotherapy and adoptive transfer of autologous tumor antigen-specific T lymphocytes in patients with metastatic melanoma. J Immunother. 2002 May-Jun;25(3):243-51. doi: 10.1097/01.CJI.0000016820.36510.89.
PubMed 12000866
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of Metastatic Cancer That Expresses Her-2 Using Lymphodepleting Conditioning Followed by Infusion of Anti-Her-2 Gene Engineered Lymphocytes
- ClinicalTrials.gov ID
- NCT00924287
- Acronym / sponsor ID
- 090041
- Conditions
- Metastatic Cancer
- Keywords
- Metastatic Cancer, Tumor Regression, Immunotherapy, Safety, Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: This study was terminated after the first patient treated on study died as a result of the treatment.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Nov 2008
- Primary completion
- Dec 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 18 Jun 2009 (estimated)
- Results
- Posted 14 Feb 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- Human epidermal growth factor receptor-2 (Her-2) is a gene found in both normal cells and cancer cells. Extra copies of the gene (overexpression) can cause too many Her-2 proteins (receptors) to appear on the cell surface and cause tumors to grow.
- An experimental procedure developed for treating patients with cancer uses blood cells found in their tumors or bloodstream. The cells are genetically modified using the anti-Her-2 gene and a type of virus. The modified cells (anti-Her-2 cells) are grown in the laboratory and then given back to the patient to try to decrease the size of the tumors. This is called gene therapy.
Objectives:
- To determine whether advanced cancers that overexpress Her-2 can be treated effectively with lymphocytes (white blood cells) that have been genetically engineered to contain an anti-Her-2 protein.
Eligibility:
- Patients 18 years of age and older with metastatic cancer (cancer that has spread beyond the original site) and for whom standard treatments are not effective.
- Patient's tumor overexpresses Her-2.
Design:
- Workup with scans, x-rays and other tests.
- Leukapheresis to obtain cells for preparing the anti-Her-2 cells for later infusion.
- 1 week of chemotherapy to prepare the immune system for receiving the anti-Her-2 cells.
- Infusion of anti-Her-2 cells, followed by interleukin-2 (IL-2) treatment. The cells are given as an infusion through a vein. IL-2 is given as a 15-minute infusion through a vein every 8 hours for a maximum of 15 doses.
- Periodic follow-up clinic visits after hospital discharge for physical examination, review of treatment side effects, laboratory tests and scans every 1 to 6 months.
Detailed description
Background:
- We have constructed a single retroviral vector that contains a chimeric T cell receptor (CAR) that recognizes the Her-2 tumor antigen, which can be used to mediate genetic transfer of this CAR with high efficiency (greater than 30%) without the need to perform any selection.
- In co-cultures with Her-2 positive tumors, anti-Her-2 CAR transduced T cells secreted significant amount of interferon-gamma (IFN-gamma) (Her-2 high specificity).
Objectives:
Primary objectives:
- To evaluate the safety of the administration of anti-Her-2 -CAR engineered peripheral blood lymphocytes in patients receiving the non-myeloablative conditioning regimen and aldesleukin.
- Determine if the administration of anti-Her-2 -CAR engineered peripheral blood lymphocytes and aldesleukin to patients following a nonmyeloablative but lymphoid depleting preparative regimen will result in clinical tumor regression in patients with metastatic cancer that expresses the Her-2 antigen.
Secondary objective:
- Determine the in vivo survival of CAR gene-engineered cells.
Eligibility:
Patients who are 18 years of age or older must have
- metastatic cancer whose tumors express the Her-2 antigen;
- previously received and have been a non-responder to or recurred after standard care for metastatic disease;
Patients may not have:
- contraindications for high dose aldesleukin administration.
Design:
- Peripheral blood mononuclear cell (PBMC) obtained by leukapheresis (approximately 5 times 10^9 cells) will be cultured in the presence of anti-CD3 (OKT3) and aldesleukin in order to stimulate T-cell growth.
- Transduction is initiated by exposure of approximately 10^8 to 5 times 10^8 cells to retroviral vector supernatant containing the anti-Her-2 CAR genes .
- Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous (IV) infusion of ex vivo tumor reactive, CAR genetransduced PBMC plus IV aldesleukin (720,000 IU/kg q8h for a maximum of 15 doses).
- Patients will undergo complete evaluation of tumor with physical examination, computed tomography (CT) of the chest, abdomen and pelvis and clinical laboratory evaluation four to six weeks after treatment. If the patient has stable disease (SD) or tumor shrinkage, repeat complete evaluations will be performed every 1-3 months. After the first year, patients continuing to respond will continue to be followed with this evaluation every 3-4 months until off study criteria are met.
- The study will be conducted using a Phase I/II optimal design. The protocol will proceed in a phase 1 dose escalation design, with three cohorts. Should a single patient experience a dose limiting toxicity (DLT) at a particular dose level, three more patients would be treated at that dose to confirm that no greater than 1/6 patients have a DLT prior to proceeding to the next higher level. If a level with 2 or more DLTs in 3-6 patients has been identified, three additional patients will be accrued at the next-lowest dose, for a total of 6, in order to further characterize the safety of the maximum tolerated dose prior to starting the phase II portion. If a dose limiting toxicity occurs in the first cohort, that cohort will be expanded to 6 patients. If 2 DLTs are encountered in this cohort, the study will be terminated.
- Once the maximum tolerated dose (MTD) has been determined, the study then would proceed to the phase II portion. Patients will be entered into two cohorts based on histology: cohort 1 will include patients with metastatic breast cancer, and cohort 2 will include patients with other types of metastatic cancer that express Her-2.
- For each of the 2 strata evaluated, the study will be conducted using a phase II optimal design where initially 21 evaluable patients will be enrolled. For each of these two arms of the trial, if 0 or 1 of the 21 patients experiences a clinical response, then no further patients will be enrolled but if 2 or more of the first 21 evaluable patients enrolled have a clinical response, then accrual will continue until a total of 41 evaluable patients have been enrolled in that stratum.
- The objective will be to determine if the combination of high dose aldesleukin, lymphocyte depleting chemotherapy, and anti-Her-2 CAR-gene engineered lymphocytes is able to be associated with a clinical response rate that can rule out 5% (p0=0.05) in favor of a modest 20% partial response (PR) + complete response (CR) rate (p1=0.20).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Metastatic Cancer | Experimental | Drug: in vitro tumor reactive, chimeric T cell receptor (CAR ) gene-transduced PBL plus IV aldesleukin, Drug: Cyclophosphamide, Drug: Fludarabine, Drug: MesnaCancer that has invaded other parts of the body |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
Key exclusion criteria (10 listed)
- Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
- Active systemic infections; coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system; myocardial infarction; cardiac arrhythmias; obstructive or restrictive pulmonary disease.
- Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
- Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities).
- Concurrent Systemic steroid therapy
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 |
|---|---|---|
| in vitro tumor reactive, chimeric T cell receptor (CAR ) gene-transduced PBL plus IV aldesleukinAlso: Proleukin, IL-2, Interleukin-2720,000 IU/kg every 8 hours for a maximum of 15 doses | Drug | Metastatic Cancer |
| CyclophosphamideAlso: Cytoxan, Neosar, Endoxan, Procytox60 mg/kg/day x 2 days intravenously (IV) in 250 ml 5% dextrose in water (D5W) with mesna 15 mg/kg/day x 2 days over 1 hour | Drug | Metastatic Cancer |
| FludarabineAlso: Fludara25 mg/m^2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days. | Drug | Metastatic Cancer |
| MesnaAlso: Mesnex, Uromitexan3 mg/kg/hour intravenously diluted in a suitable diluent over 23 hours after each cyclophosphamide dose. | Drug | Metastatic Cancer |
Primary outcome
Number of Participants With an Objective Clinical Tumor Regression Response
Time frame: 12 days
Response Evaluation Criteria in Solid Tumors (RECIST) are used to determine objective clinical response. Complete Rresponse (CR) is the disappearance of all target lesions, partial response (PR) is at least a 30% decrease in the target lesions, progressive disease (PD) is at least a 20% increase in the target lesions or appearance of one or more new lesions, and stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Number of Participants With Adverse Events
Time frame: 12 days
Here are the number of participants with adverse events. For the detailed list of adverse events see the adverse event module.
1 secondary outcome
Number of Participants With In Vivo Survival of Transfused Cells
Time frame: 12 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 7516411Kawakami Y, Eliyahu S, Sakaguchi K, Robbins PF, Rivoltini L, Yannelli JR, Appella E, Rosenberg SA. Identification of the immunodominant peptides of the MART-1 human melanoma antigen recognized by the majority of HLA-A2-restricted tumor infiltrating lymphocytes. J Exp Med. 1994 Jul 1;180(1):347-52. doi: 10.1084/jem.180.1.347.
- Background: PubMed 11565838Dudley ME, Wunderlich J, Nishimura MI, Yu D, Yang JC, Topalian SL, Schwartzentruber DJ, Hwu P, Marincola FM, Sherry R, Leitman SF, Rosenberg SA. Adoptive transfer of cloned melanoma-reactive T lymphocytes for the treatment of patients with metastatic melanoma. J Immunother. 2001 Jul-Aug;24(4):363-73. doi: 10.1097/00002371-200107000-00012.
- Background: PubMed 12000866Dudley ME, Wunderlich JR, Yang JC, Hwu P, Schwartzentruber DJ, Topalian SL, Sherry RM, Marincola FM, Leitman SF, Seipp CA, Rogers-Freezer L, Morton KE, Nahvi A, Mavroukakis SA, White DE, Rosenberg SA. A phase I study of nonmyeloablative chemotherapy and adoptive transfer of autologous tumor antigen-specific T lymphocytes in patients with metastatic melanoma. J Immunother. 2002 May-Jun;25(3):243-51. doi: 10.1097/01.CJI.0000016820.36510.89.
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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.
Steven A Rosenberg, 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 1/2 study testing in vitro tumor reactive, chimeric T cell receptor (CAR ) gene-transduced PBL plus IV aldesleukin, Cyclophosphamide and Fludarabine in people with Metastatic Cancer, 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 25 inclusion and 10 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: stopped early, as of the sponsor's last update on 28 Oct 2015. 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 14 Feb 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 Objective Clinical Tumor Regression Response (time frame: 12 days). The study lists 2 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 NCT00924287, 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 28 Oct 2015.