Cervical CancerPhase 1/2NCT02111850
T Cell Receptor Immunotherapy Targeting MAGE-A3 for Patients With Metastatic Cancer Who Are HLA-DP0401 Positive
A Phase 1/2 study testing Anti-MAGE-A3-DP4 T Cell Receptor (TCR) Peripheral Blood Lymphocytes (PBL), Cyclophosphamide and Fludarabine in people with Cervical Cancer and Renal Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Background: The National Cancer Institute (NCI) Surgery Branch has developed an experimental therapy for treating patients with metastatic cancer that involves taking white blood cells from the patient, growing them in the laboratory in large numbers, genetically modifying these specific cells with a type of virus… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Cervical Cancer, Renal Cancer, Urothelial Cancer
- What is being tested?
- Anti-MAGE-A3-DP4 T Cell Receptor (TCR) Peripheral Blood Lymphocytes (PBL), Cyclophosphamide and Fludarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Feb 2014to 24 Mar 2021
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant.
- Active systemic infections, (e.g.: requiring anti-infective treatment), coagulation disorders or any other active major medical illnesses
- 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.
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- History of any cardiac events including coronary revascularization or ischemic symptoms.
- Documented left ventricular ejection fraction (LVEF) of less than or equal to 45% testing is required in patients who are
- greater than or equal to 65 years old
- Clinically significant atrial and or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or have a history of ischemic heart disease, or chest pain.
- Documented forced expiratory volume (FEV1) less than or equal to 60% predicted tested in patients with:
- A prolonged history of cigarette smoking (20 pk/year of smoking within the past 2 years).
- Symptoms of respiratory dysfunction
- Patients who are receiving any other investigational agents.
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: A Phase I/II Study of the Treatment of Metastatic Cancer That Expresses MAGE-A3 Using Lymphodepleting Conditioning Followed by Infusion of HLA-DP0401/0402 Restricted Anti-MAGE-A3 TCR-Gene Engineered Lymphocytes and Aldesleukin
Background:
The National Cancer Institute (NCI) Surgery Branch has developed an experimental therapy for treating patients with metastatic cancer that involves taking white blood cells from the patient, growing them in the laboratory in large numbers, genetically modifying these specific cells with a type of virus (retrovirus) to attack only the tumor cells, and then giving the cells back to the patient. This type of therapy is called gene transfer. In this protocol, we are modifying the patient s white blood cells with a retrovirus that has the gene for anti-Melanoma antigen family A, 3 (MAGE-A3)-DP0401/0402 incorporated in the retrovirus.
Read more
Objective:
The purpose of this study is to determine a safe number of these cells to infuse and to see if these particular tumor-fighting cells (anti-MAGE-A3-DP0401/0402 cells) cause tumors to shrink and to be certain the treatment is safe.
Eligibility:
- Adult's age 18-70 with metastatic cancer expressing the MAGE-A3 molecule.
Design:
- Work up stage: Patients will be seen as an outpatient at the National Institutes of Health (NIH) clinical Center and undergo a history and physical examination, scans, x-rays, lab tests, and other tests as needed
- Leukapheresis: If the patients meet all of the requirements for the study, they will undergo leukapheresis to obtain white blood cells to make the anti-MAGE-A3-DP0401/0402 cells. {Leukapheresis is a common procedure, which removes only the white blood cells from the patient.}
- Treatment: Once their cells have grown, the patients will be admitted to the hospital for the conditioning chemotherapy, the anti-MAGE-A3-DP0401/0402 cells and aldesleukin. They will stay in the hospital for approximately 4 weeks for the treatment.
- Follow up: Patients will return to the clinic for a physical exam, review of side effects, lab tests, and scans about every 1-3 months for the first year, and then every 6 months to 1 year as long as their tumors are shrinking.
Read the detailed description
Background:
- We have constructed a single retroviral vector that contains both and $ <= chains of a T cell receptor (TCR) that recognizes the DP0401/0402 restricted Melanoma antigen family A, 3 (MAGE-A3) tumor antigen, which can be used to mediate genetic transfer of this TCR with high efficiency.
- In co-cultures with HLA-DP0401/0402 and MAGE-A3 double positive tumors, the anti- MAGE-A3- DP0401/0402 restricted (anti-MAGE-A3-DP4) TCR transduced T cells secreted significant amounts of Interferon gamma (IFN-y) with high specificity.
Objectives:
Primary objectives:
- Determine a safe dose of the administration of autologous cluster of differentiation 4 (CD4) cells transduced with an anti-MAGE-A3-DP0401/0402 restricted (MAGE-A3-DP4) TCR and aldesleukin to patients following a nonmyeloablative but lymphoid depleting preparative regimen.
- Determine if this approach will result in objective tumor regression in patients with metastatic cancer expressing MAGE-A3-DP4.
- Determine the toxicity profile of this treatment regimen.
Eligibility:
Patients who are human leukocyte antigens (HLA)-DP0401/0402 positive and 18 years of age or older must have
- Metastatic cancer whose tumors express the MAGE-A3-DP4 antigen.
- Previously received and have been a non-responder to or recurred following at least one first line treatment for metastatic disease.
Patients may not have:
- Contraindications for high dose aldesleukin administration.
Design:
- PBMC obtained by leukapheresis will be enriched for CD4 cells and transduced with the retroviral vector supernatant encoding the anti-MAGE-A3-DP4 TCR.
- The study will begin in a standard phase 1 dose escalation. After the maximum tolerated dose (MTD) cell dose has been determined, patients will be enrolled into the phase 2 portion of the trial at the MTD established during the phase 1 portion of the study. In the phase 2 portion, patients will be entered into two cohorts: cohort 1 will include patients with metastatic melanoma; cohort 2 will include patients with renal cancer and other types of metastatic cancer.
- Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of ex vivo tumor reactive, TCR gene-transduced peripheral blood mononuclear cells (PBMC) plus intravenous (IV) aldesleukin.
- Patients will undergo complete evaluation of tumor response every 1-6 months until off study criteria are met.
- For each of the 2 strata evaluated in the phase 2 portion, the study will be conducted using a phase 2 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.
- For both strata, the objective will be to determine if the treatment regimen 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
- Cervical Cancer, Renal Cancer, Urothelial Cancer, Melanoma, Breast Cancer
- Being tested
- Anti-MAGE-A3-DP4 T Cell Receptor (TCR) Peripheral Blood Lymphocytes (PBL), Cyclophosphamide, Fludarabine, Aldesleukin
- Keywords
- Gene Therapy, Tumor Regression, Immunotherapy, Adoptive Cell Therapy
- Medical subject headings
- Uterine Cervical Neoplasms, Kidney Neoplasms, Melanoma, Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anti-MAGE-A3-DP4 T Cell Receptor (TCR) Peripheral Blood Lymphocytes (PBL)Biological
Day 0: cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes
CyclophosphamideDrug
Also called Cytoxan
Days -7 and -6: Cyclophosphamide 60 mg/kg/day X 2 days intravenous (IV) in 250 ml dextrose 5 % in water (D5W) with Mesna 15 mg/kg /day X 2 days over 1 hour.
FludarabineDrug
Also called Fludara
Days -7 to -3: Fludarabine 25 mg/m^2 /day intravenous piggy-back (IVPB) daily over 30 minutes for 5 days.
AldesleukinDrug
Also called Proleukin
Aldesleukin 720,000 IU/kg intravenous (IV) (based on total body weight) over 15 minutes every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum 15 doses).
| Study group | Role | What they receive |
|---|---|---|
| 1/Phase I Experimental Therapy | Experimental | Non-myeloablative lymphodepleting preparative regimen of cyclophosphamide and fludarabine + Anti-Melanoma antigen family A, 3 (MAGE-A3)-DP4 T cell receptor (TCR) peripheral blood lymphocytes (PBL) + high-dose aldesleukin Receives: Biological: Anti-MAGE-A3-DP4 T Cell Receptor (TCR) Peripheral Blood Lymphocytes (PBL); Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Aldesleukin |
| 2/Phase II Experimental Therapy | Experimental | Non-myeloablative lymphodepleting preparative regimen of cyclophosphamide and fludarabine + Anti-Melanoma antigen family A, 3 (MAGE-A3)-DP4 T cell receptor (TCR) peripheral blood lymphocytes (PBL) + high-dose aldesleukin Receives: Biological: Anti-MAGE-A3-DP4 T Cell Receptor (TCR) Peripheral Blood Lymphocytes (PBL); Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Aldesleukin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Cell Dose (MTD) of Cluster of Differentiation 4 (CD4) Cells Transduced With an Anti-MAGE-A3-DP0401/0402 Restricted (MAGE-A3-DP4) T Cell Receptor and Aldesleukin
Highest dose at which less than or equal to 1 of 6 patients experienced a dose-limiting toxicity (DLT) (all grade 3 and greater toxicities with the exception of myelosuppression and grade 3 fever, for example) or the highest dose level studied if DLTs are not observed at any of the dose levels.
Measured: Before progression to next-higher dose level, at least two weeks
Percentage of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression)
Percentage of participants who have a clinical response to treatment (objective tumor regression) measured by the Response Evaluation Criteria in Solid Tumors (RECIST)v1.0. Complete response is disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the longest diameter of target lesions. Progression is at least a 20% increase in the sum of longest diameter of target lesions or the appearance of one or more new lesions. And stable disease is neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease.
Measured: 6 and 12 weeks after cell infusion, then every 3 months x3, then every 6 months x2 years, then per principal investigator discretion, approximately 6 years
Number of Adverse Events With Grades ≥1 That Are Possibly, Probably, and/or Definitely Related to Treatment
Aggregate of all adverse events with Grades ≥1 that are possibly, probably, and/or definitely related to treatment. Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life-threatening, and Grade 5 is death related to adverse events.
Measured: 6 weeks after cell infusion
Secondary outcomes (1)
Number of Engineered T Cell Receptor (TCR) Cells That Survived at 4 Weeks
T cell receptor (TCR) and vector presence was quantitated in peripheral blood mononuclear cells (PBMC) samples using flow cytometry. It is a process by which cells are suspended in a liquid so they can be counted.
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2014 (estimated)
- Study start7 Feb 2014
- Primary completion24 Mar 2021
- Study completion24 Mar 2021
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 Cervical 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
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 21 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 Cancer Institute (NCI)
- Investigators
- Steven A Rosenberg, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02111850
- Sponsor's protocol ID
- 140052
- Other IDs
- 14-C-0052
- Status last verified
- Mar 2022
- First submitted
- 9 Apr 2014
- Last updated
- 29 Mar 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Morgan RA, Dudley ME, Yu YY, Zheng Z, Robbins PF, Theoret MR, Wunderlich JR, Hughes MS, Restifo NP, Rosenberg SA. High efficiency TCR gene transfer into primary human lymphocytes affords avid recognition of melanoma tumor antigen glycoprotein 100 and does not alter the recognition of autologous melanoma antigens. J Immunol. 2003 Sep 15;171(6):3287-95. doi: 10.4049/jimmunol.171.6.3287.
PubMed 12960359Suri A. Cancer testis antigens--their importance in immunotherapy and in the early detection of cancer. Expert Opin Biol Ther. 2006 Apr;6(4):379-89. doi: 10.1517/14712598.6.4.379.
PubMed 16548764Robbins PF, Morgan RA, Feldman SA, Yang JC, Sherry RM, Dudley ME, Wunderlich JR, Nahvi AV, Helman LJ, Mackall CL, Kammula US, Hughes MS, Restifo NP, Raffeld M, Lee CC, Levy CL, Li YF, El-Gamil M, Schwarz SL, Laurencot C, Rosenberg SA. Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J Clin Oncol. 2011 Mar 1;29(7):917-24. doi: 10.1200/JCO.2010.32.2537. Epub 2011 Jan 31.
PubMed 21282551
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of the Treatment of Metastatic Cancer That Expresses MAGE-A3 Using Lymphodepleting Conditioning Followed by Infusion of HLA-DP0401/0402 Restricted Anti-MAGE-A3 TCR-Gene Engineered Lymphocytes and Aldesleukin
- ClinicalTrials.gov ID
- NCT02111850
- Acronym / sponsor ID
- 140052
- Conditions
- Cervical Cancer, Renal Cancer, Urothelial Cancer, Melanoma, Breast Cancer
- Keywords
- Gene Therapy, Tumor Regression, Immunotherapy, Adoptive Cell Therapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 7 Feb 2014 (actual)
- Primary completion
- 24 Mar 2021 (actual)
- Study completion
- 24 Mar 2021 (actual)
- First posted
- 11 Apr 2014 (estimated)
- Results
- Posted 29 Mar 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
The National Cancer Institute (NCI) Surgery Branch has developed an experimental therapy for treating patients with metastatic cancer that involves taking white blood cells from the patient, growing them in the laboratory in large numbers, genetically modifying these specific cells with a type of virus (retrovirus) to attack only the tumor cells, and then giving the cells back to the patient. This type of therapy is called gene transfer. In this protocol, we are modifying the patient s white blood cells with a retrovirus that has the gene for anti-Melanoma antigen family A, 3 (MAGE-A3)-DP0401/0402 incorporated in the retrovirus.
Objective:
The purpose of this study is to determine a safe number of these cells to infuse and to see if these particular tumor-fighting cells (anti-MAGE-A3-DP0401/0402 cells) cause tumors to shrink and to be certain the treatment is safe.
Eligibility:
- Adult's age 18-70 with metastatic cancer expressing the MAGE-A3 molecule.
Design:
- Work up stage: Patients will be seen as an outpatient at the National Institutes of Health (NIH) clinical Center and undergo a history and physical examination, scans, x-rays, lab tests, and other tests as needed
- Leukapheresis: If the patients meet all of the requirements for the study, they will undergo leukapheresis to obtain white blood cells to make the anti-MAGE-A3-DP0401/0402 cells. {Leukapheresis is a common procedure, which removes only the white blood cells from the patient.}
- Treatment: Once their cells have grown, the patients will be admitted to the hospital for the conditioning chemotherapy, the anti-MAGE-A3-DP0401/0402 cells and aldesleukin. They will stay in the hospital for approximately 4 weeks for the treatment.
- Follow up: Patients will return to the clinic for a physical exam, review of side effects, lab tests, and scans about every 1-3 months for the first year, and then every 6 months to 1 year as long as their tumors are shrinking.
Detailed description
Background:
- We have constructed a single retroviral vector that contains both and $ <= chains of a T cell receptor (TCR) that recognizes the DP0401/0402 restricted Melanoma antigen family A, 3 (MAGE-A3) tumor antigen, which can be used to mediate genetic transfer of this TCR with high efficiency.
- In co-cultures with HLA-DP0401/0402 and MAGE-A3 double positive tumors, the anti- MAGE-A3- DP0401/0402 restricted (anti-MAGE-A3-DP4) TCR transduced T cells secreted significant amounts of Interferon gamma (IFN-y) with high specificity.
Objectives:
Primary objectives:
- Determine a safe dose of the administration of autologous cluster of differentiation 4 (CD4) cells transduced with an anti-MAGE-A3-DP0401/0402 restricted (MAGE-A3-DP4) TCR and aldesleukin to patients following a nonmyeloablative but lymphoid depleting preparative regimen.
- Determine if this approach will result in objective tumor regression in patients with metastatic cancer expressing MAGE-A3-DP4.
- Determine the toxicity profile of this treatment regimen.
Eligibility:
Patients who are human leukocyte antigens (HLA)-DP0401/0402 positive and 18 years of age or older must have
- Metastatic cancer whose tumors express the MAGE-A3-DP4 antigen.
- Previously received and have been a non-responder to or recurred following at least one first line treatment for metastatic disease.
Patients may not have:
- Contraindications for high dose aldesleukin administration.
Design:
- PBMC obtained by leukapheresis will be enriched for CD4 cells and transduced with the retroviral vector supernatant encoding the anti-MAGE-A3-DP4 TCR.
- The study will begin in a standard phase 1 dose escalation. After the maximum tolerated dose (MTD) cell dose has been determined, patients will be enrolled into the phase 2 portion of the trial at the MTD established during the phase 1 portion of the study. In the phase 2 portion, patients will be entered into two cohorts: cohort 1 will include patients with metastatic melanoma; cohort 2 will include patients with renal cancer and other types of metastatic cancer.
- Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of ex vivo tumor reactive, TCR gene-transduced peripheral blood mononuclear cells (PBMC) plus intravenous (IV) aldesleukin.
- Patients will undergo complete evaluation of tumor response every 1-6 months until off study criteria are met.
- For each of the 2 strata evaluated in the phase 2 portion, the study will be conducted using a phase 2 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.
- For both strata, the objective will be to determine if the treatment regimen 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
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1/Phase I Experimental Therapy | Experimental | Biological: Anti-MAGE-A3-DP4 T Cell Receptor (TCR) Peripheral Blood Lymphocytes (PBL), Drug: Cyclophosphamide, Drug: Fludarabine, Drug: AldesleukinNon-myeloablative lymphodepleting preparative regimen of cyclophosphamide and fludarabine + Anti-Melanoma antigen family A, 3 (MAGE-A3)-DP4 T cell receptor (TCR) peripheral blood lymphocytes (PBL) + high-dose aldesleukin |
| 2/Phase II Experimental Therapy | Experimental | Biological: Anti-MAGE-A3-DP4 T Cell Receptor (TCR) Peripheral Blood Lymphocytes (PBL), Drug: Cyclophosphamide, Drug: Fludarabine, Drug: AldesleukinNon-myeloablative lymphodepleting preparative regimen of cyclophosphamide and fludarabine + Anti-Melanoma antigen family A, 3 (MAGE-A3)-DP4 T cell receptor (TCR) peripheral blood lymphocytes (PBL) + high-dose aldesleukin |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (14 listed)
- Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant.
- Active systemic infections, (e.g.: requiring anti-infective treatment), coagulation disorders or any other active major medical illnesses
- 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 |
|---|---|---|
| Anti-MAGE-A3-DP4 T Cell Receptor (TCR) Peripheral Blood Lymphocytes (PBL)Day 0: cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes | Biological | 1/Phase I Experimental Therapy, 2/Phase II Experimental Therapy |
| CyclophosphamideAlso: CytoxanDays -7 and -6: Cyclophosphamide 60 mg/kg/day X 2 days intravenous (IV) in 250 ml dextrose 5 % in water (D5W) with Mesna 15 mg/kg /day X 2 days over 1 hour. | Drug | 1/Phase I Experimental Therapy, 2/Phase II Experimental Therapy |
| FludarabineAlso: FludaraDays -7 to -3: Fludarabine 25 mg/m^2 /day intravenous piggy-back (IVPB) daily over 30 minutes for 5 days. | Drug | 1/Phase I Experimental Therapy, 2/Phase II Experimental Therapy |
| AldesleukinAlso: ProleukinAldesleukin 720,000 IU/kg intravenous (IV) (based on total body weight) over 15 minutes every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum 15 doses). | Drug | 1/Phase I Experimental Therapy, 2/Phase II Experimental Therapy |
Primary outcome
Maximum Tolerated Cell Dose (MTD) of Cluster of Differentiation 4 (CD4) Cells Transduced With an Anti-MAGE-A3-DP0401/0402 Restricted (MAGE-A3-DP4) T Cell Receptor and Aldesleukin
Time frame: Before progression to next-higher dose level, at least two weeks
Highest dose at which less than or equal to 1 of 6 patients experienced a dose-limiting toxicity (DLT) (all grade 3 and greater toxicities with the exception of myelosuppression and grade 3 fever, for example) or the highest dose level studied if DLTs are not observed at any of the dose levels.
Percentage of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression)
Time frame: 6 and 12 weeks after cell infusion, then every 3 months x3, then every 6 months x2 years, then per principal investigator discretion, approximately 6 years
Percentage of participants who have a clinical response to treatment (objective tumor regression) measured by the Response Evaluation Criteria in Solid Tumors (RECIST)v1.0. Complete response is disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the longest diameter of target lesions. Progression is at least a 20% increase in the sum of longest diameter of target lesions or the appearance of one or more new lesions. And stable disease is neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease.
Number of Adverse Events With Grades ≥1 That Are Possibly, Probably, and/or Definitely Related to Treatment
Time frame: 6 weeks after cell infusion
Aggregate of all adverse events with Grades ≥1 that are possibly, probably, and/or definitely related to treatment. Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life-threatening, and Grade 5 is death related to adverse events.
1 secondary outcome
Number of Engineered T Cell Receptor (TCR) Cells That Survived at 4 Weeks
Time frame: 4 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 12960359Morgan RA, Dudley ME, Yu YY, Zheng Z, Robbins PF, Theoret MR, Wunderlich JR, Hughes MS, Restifo NP, Rosenberg SA. High efficiency TCR gene transfer into primary human lymphocytes affords avid recognition of melanoma tumor antigen glycoprotein 100 and does not alter the recognition of autologous melanoma antigens. J Immunol. 2003 Sep 15;171(6):3287-95. doi: 10.4049/jimmunol.171.6.3287.
- Background: PubMed 16548764Suri A. Cancer testis antigens--their importance in immunotherapy and in the early detection of cancer. Expert Opin Biol Ther. 2006 Apr;6(4):379-89. doi: 10.1517/14712598.6.4.379.
- Background: PubMed 21282551Robbins PF, Morgan RA, Feldman SA, Yang JC, Sherry RM, Dudley ME, Wunderlich JR, Nahvi AV, Helman LJ, Mackall CL, Kammula US, Hughes MS, Restifo NP, Raffeld M, Lee CC, Levy CL, Li YF, El-Gamil M, Schwarz SL, Laurencot C, Rosenberg SA. Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J Clin Oncol. 2011 Mar 1;29(7):917-24. doi: 10.1200/JCO.2010.32.2537. Epub 2011 Jan 31.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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 (NCI)
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 Anti-MAGE-A3-DP4 T Cell Receptor (TCR) Peripheral Blood Lymphocytes (PBL), Cyclophosphamide and Fludarabine in people with Cervical Cancer and Renal 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 0 inclusion and 14 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 29 Mar 2022. 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 29 Mar 2022). 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?
Maximum Tolerated Cell Dose (MTD) of Cluster of Differentiation 4 (CD4) Cells Transduced With an Anti-MAGE-A3-DP0401/0402 Restricted (MAGE-A3-DP4) T Cell Receptor and Aldesleukin (time frame: Before progression to next-higher dose level, at least two weeks). 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 NCT02111850, 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 29 Mar 2022.