Metastatic Cancer Clinical Trial
Official title:
Phase I/II Study of Metastatic Cancer That Expresses MAGE-A3/12 Using Lymphodepleting Conditioning Followed by Infusion of Anti-MAGE-A3/12 TCR-Gene Engineered Lymphocytes
Background:
- MAGE-A3/12 is a type of protein commonly found on certain types of cancer cells,
particularly in metastatic cancer. Researchers have developed a process to take lymphocytes
(white blood cells) from cancer patients, modify them in the laboratory to target cancer
cells that contain MAGE-A3/12, and return them to the patient to help attack and kill the
cancer cells. These modified white blood cells are an experimental treatment, but
researchers are interested in determining their safety and effectiveness as a possible
treatment for cancers that involve MAGE-A3/12.
Objectives:
- To evaluate the safety and effectiveness of anti-MAGE-A3/12 lymphocytes as a treatment for
metastatic cancers that have not responded to standard treatment.
Eligibility:
- Individuals at least 18 years of age who have been diagnosed with metastatic melanoma,
renal cell cancer, or another type of metastatic cancer that has not responded to standard
treatment.
Design:
- Participants will be screened with a full medical history and physical examination, as
well as blood and urine tests, tumor samples, and imaging studies.
- Participants will have leukapheresis to collect enough white blood cells for
modification in the laboratory.
- Seven days before the start of anti-MAGE-A3/12 treatment, participants will have
chemotherapy with cyclophosphamide and fludarabine to suppress the immune system in
preparation for the treatment.
- After the last dose of chemotherapy, participants will receive the anti-MAGE-A3/12
cells as an infusion for 20 to 30 minutes, followed by a dose of interleukin-2 to keep
the anti-MAGE-A3/12 cells alive and active as long as possible. Participants will also
receive filgrastim to encourage the production of blood cells.
- Participants will remain in the hospital to be monitored for possible side effects, and
after release from the hospital will have regular followup exams with blood samples and
imaging studies to evaluate the effectiveness of the treatment....
Background
We have constructed a single retroviral vector that contains both alpha and beta chains of a
T cell receptor (TCR) that recognizes the MAGE-A3/12 tumor antigen, which can be used to
mediate genetic transfer of this TCR with high efficiency (> 30%) without the need to
perform any selection.
In co-cultures with human leukocyte antigen serotype within HLA-A serotype group (HLA-A2)
and MAGE-A3/12 double positive tumors, anti-MAGE-A3/12 TCR transduced T cells secreted
significant amounts of Interferon (IFN)-gamma with high specificity.
Objectives:
Primary objectives:
- Determine if the administration of anti-MAGE-A3/12 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 MAGE-A3/12 antigen.
- Determine the toxicity profile of this treatment regimen
Secondary objectives:
-Determine the in vivo survival of TCR gene-engineered cells.
Eligibility:
Patients who are human leukocyte antigen (HLA)-A*0201 positive and 18 years of age or older
must have:
- metastatic cancer whose tumors express the MAGE-A3/12 antigen;
- previously received and have been a non-responder to or recurred following standard
care for metastatic disease;
Patients may not have:
-contraindications for high dose aldesleukin administration.
Design:
PBMC obtained by leukapheresis (approximately 10^10) 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 10^7 to 5 X 10^8 cells to retroviral
vector supernatant containing the anti-MAGE-A3/12 TCR genes.
The study will begin by evaluating the safety of two ranges of cells, 5 x 10^9 - 3 x 10^10,
and greater than 3 x 10^10- 1 x 10^11 in a standard phase I dose escalation fashion using a
3+3 design. Once this safety has been confirmed, patients will be enrolled into the phase 2
portion of the trial using up to 1 x 10^11 cells. In the phase 2 portion, patients will be
entered into two cohorts based on histology: cohort 1 will include patients with metastatic
melanoma or renal cell cancer; cohort 2 will include patients with 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 (720,000 IU/kg every (q)8h 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.
For each of the 2 strata evaluated in the phase 2 portion, 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.
For both strata, the objective will be to determine if the combination of high dose
aldesleukin, lymphocyte depleting chemotherapy, and anti-MAGE-A3/12 TCR-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).
;
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05094804 -
A Study of OR2805, a Monoclonal Antibody Targeting CD163, Alone and in Combination With Anticancer Agents
|
Phase 1/Phase 2 | |
Enrolling by invitation |
NCT00068003 -
Harvesting Cells for Experimental Cancer Treatments
|
||
Recruiting |
NCT05798611 -
Study of ART0380 in Patients With Biologically Selected Solid Tumors
|
Phase 2 | |
Not yet recruiting |
NCT04931420 -
Study Comparing Standard of Care Chemotherapy With/ Without Sequential Cytoreductive Surgery for Patients With Metastatic Foregut Cancer and Undetectable Circulating Tumor-Deoxyribose Nucleic Acid Levels
|
Phase 2 | |
Recruiting |
NCT05566574 -
A Study of RP-3500 in Combination With Standard Radiation Therapy in People With Solid Tumor Cancer
|
Phase 1/Phase 2 | |
Recruiting |
NCT05036681 -
A Phase II Study of Futibatinib and Pembrolizumab in Metastatic Microsatellite Stable Endometrial Carcinoma
|
Phase 2 | |
Withdrawn |
NCT00005030 -
SCH 66336 Before Surgery in Treating Patients With Colorectal Cancer That Has Metastasized to the Liver
|
Phase 1 | |
Recruiting |
NCT05525858 -
KPMNG Study of MOlecular Profiling Guided Therapy Based on Genomic Alterations in Advanced Solid Tumors II
|
||
Recruiting |
NCT04085029 -
Role of Ablative Radiotherapy in the Management of Metastatic Disease: A Patient Data Registry
|
||
Recruiting |
NCT06058988 -
Trastuzumab Deruxtecan (T-DXd) for People With Brain Cancer
|
Phase 2 | |
Not yet recruiting |
NCT05981170 -
Rurality Adapted Physical Activity Sport Health
|
||
Not yet recruiting |
NCT03058809 -
Evaluation of Viatarâ„¢ Oncopheresis System in Removing CTC From Whole Blood
|
Phase 1/Phase 2 | |
Completed |
NCT02529553 -
A Study of LY3076226 in Participants With Advanced or Metastatic Cancer
|
Phase 1 | |
Terminated |
NCT01929941 -
An Open-Label Study of a Novel JAK-inhibitor, INCB047986, Given in Patients With Advanced Malignancies
|
Phase 1 | |
Terminated |
NCT00918645 -
Calcium-41 (41Ca) Chloride Aqueous Solution in Diagnosing Patients With Prostate Cancer and Bone Metastasis
|
N/A | |
Completed |
NCT01302808 -
Romidepsin and Erlotinib Hydrochloride in Treating Patients With Stage III or Stage IV Non-Small Cell Lung Cancer
|
Phase 1 | |
Withdrawn |
NCT00769990 -
Genistein in Treating Patients Undergoing External-Beam Radiation Therapy for Bone Metastases
|
Phase 1/Phase 2 | |
Completed |
NCT00795678 -
Chemotherapeutic Agents in Brain/Breast
|
N/A | |
Completed |
NCT00557102 -
Cetuximab and Combination Chemotherapy as First-Line Therapy in Treating Patients With Colorectal Cancer That Has Spread to the Liver and/or Lung
|
Phase 2 | |
Recruiting |
NCT00398437 -
Magnetic Resonance Imaging for the Early Detection of CNS Metastases in Women With Stage IV Breast Cancer
|
N/A |