Adoptive Transfer of Autologous T Cells Targeted to Prostate Specific Membrane Antigen (PSMA) for the Treatment of Castrate Metastatic Prostate Cancer (CMPC)

Tracking Information
First Submitted Date ICMJE	June 7, 2010
First Posted Date ICMJE	June 9, 2010
Last Update Posted Date	November 6, 2017
Study Start Date ICMJE	June 2010
Estimated Primary Completion Date	June 2018 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: June 8, 2010)	The safety and tolerability of immunotherapy [ Time Frame: 4 weeks ]; Dose escalation is based on the dose limiting toxicity (DLT). In this phase I trial, dose escalation will be based on the DLT, defined as a grade 3 or 4 toxicity (excluding alopecia, fatigue) developing after infusion of the T cells as graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events Scale (CTCAE) Version 3.0. Only toxicities that are possibly, probably, or definitely related to treatment will be considered DLTs. Patients will be observed for DLTs four weeks (28 days) from the T cell infusion
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01140373 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: June 8, 2010)	Changes in bone metastases [ Time Frame: Week 12 then every 3 months ]; Changes in biomarkers of bone metastasis and metabolism [ Time Frame: Week 4 and week 12 ]; Changes in circulating tumor cells [ Time Frame: Weeks 4, 12, 24 and every 3 months ]; Humoral and cell-mediated immunity to PSMA and other known prostate cancer antigens [ Time Frame: Weeks 12 and 24 ]; To assess patterns of change in PSA. [ Time Frame: 5 years ]; To track the persistence, accumulation, and migration of genetically retargeted anti-PSMA autologous T cells [ Time Frame: 2 years ]
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Adoptive Transfer of Autologous T Cells Targeted to Prostate Specific Membrane Antigen (PSMA) for the Treatment of Castrate Metastatic Prostate Cancer (CMPC)
Official Title ICMJE	Adoptive Transfer of Autologous T Cells Targeted to Prostate Specific Membrane Antigen (PSMA) for the Treatment of Castrate Metastatic Prostate Cancer (CMPC)
Brief Summary	This is a phase I study which will test the safety of different doses of the patients own immune cells which have been changed to help recognize and destroy the cancer cells. The investigators want to find out what effects, good and/or bad, it has on the body and on the prostate cancer. The immune cells (T cells) used in this study will be the patients own immune cells. They will be removed from the patients blood, changed in the laboratory, and then put back into their body. T cells help the body fight infections. These cells may also kill cancer cells in some cases. Right now the patients T cells are unable to kill the cancer cells. For this reason, the physician will change the T cells by putting in a gene so that they may be able to better recognize and kill the prostate cancer cells. A gene is a portion of information which comes from the DNA and tells the cell what to do. This gene will be put into the patients T cells by a weakened virus. It is hoped that this approach will help the T cells recognize the prostate cancer tumor cells and possibly kill them. The investigators have found that T cells modified in this way were able to cure a cancer similar to Chronic Lymphocytic Leukemia in mice. However, this is an entirely new treatment for prostate cancer and it is not known if it will have any beneficial or unexpected harmful effects.
Detailed Description	Not Provided
Study Type ICMJE	Interventional
Study Phase	Phase 1
Study Design ICMJE	Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Prostate Cancer
Intervention ICMJE	Biological: engineered autologous T cells Three cohorts of patients each will receive escalating doses of transduced autologous chimeric T lymphocytes at 1 x 10^7 CAR+ T cells/kg, 3 x 10^7 CAR+ T cells/kg, and 1 x 108 CAR+ T cells/kg, respectively. One patient will be initially added to the three already enrolled in cohort 1 using a new variant vector expressing the P28z CAR, and up to three patients may be added to each cohort, for a total of up to six each, in the case of Grade 3 toxicity and/or sub-optimal imaging. A 4th cohort of three patients may be added if an anti-PSMA effect is observed either immunologically or radiographically or if there is preferential targeting of the cells at a particular dose level. The dose level of the 4th cohort would be from a previously tested dose level. All patients will receive one dose of cyclophosphamide (Cy) at 300mg/m2 iv one day prior to infusion of T cells.; Drug: cyclophosphamide Three cohorts of patients each will receive escalating doses of transduced autologous chimeric T lymphocytes at 1 x 10^7 CAR+ T cells/kg, 3 x 10^7 CAR+ T cells/kg, and 1 x 10^8 CAR+ T cells/kg, respectively. One patient will be initially added to the three already enrolled in cohort 1 using a new variant vector expressing the P28z CAR, and up to three patients may be added to each cohort, for a total of up to six each, in the case of Grade 3 toxicity and/or sub-optimal imaging. A 4th cohort of three patients may be added if an anti-PSMA effect is observed either immunologically or radiographically or if there is preferential targeting of the cells at a particular dose level. The dose level of the 4th cohort would be from a previously tested dose level. All patients will receive one dose of cyclophosphamide (Cy) at 300mg/m2 iv one day prior to infusion of T cells.
Study Arms	Experimental: autologous T cells & cyclophosphamide.; This is a phase I dose escalation study to assess the safety and tolerability using increasing doses of engineered autologous T cells targeted to Prostate-Specific Membrane Antigen (PSMA) administered one day after pretreatment with cyclophosphamide.; Interventions: Biological: engineered autologous T cells; Drug: cyclophosphamide
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Active, not recruiting
Actual Enrollment ICMJE; (submitted: November 1, 2017)	13
Original Estimated Enrollment ICMJE; (submitted: June 8, 2010)	12
Estimated Study Completion Date	June 2018
Estimated Primary Completion Date	June 2018 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Male, over 18 years of age; Karnofsky Performance Scale (KPS) greater or = to 70%; Histologic confirmation of prostate cancer at Memorial Sloan-Kettering Cancer Center (MSKCC); A diagnosis of progressive castrate metastatic prostate cancer defined as one or more of the following three criteria:; Soft tissue progression defined by RECIST 1.0; Bone disease progression defined by PCWG2 with two or more new lesions on bone scan; Post-hormonal therapy rising PSA values from a hormone therapy nadir on greater or = to 3 successive determinations at least two weeks apart, where the increase above the nadir is the greater of greater or = to 2.0 ng/mL or a greater or = to 10% change (Subjects with a rise in PSA but no evidence of metastases at any time by imaging studies will NOT be eligible.); For subjects who have discontinued anti-androgen therapy, PSA rise as defined above must be documented:; Within two weeks after discontinuation if used following surgical or medical castration (second line therapy); After four weeks discontinuation if used as first line therapy.; Evidence of metastatic disease in bone on bone scan, CT scan, and/or by MRI atany time following the initial diagnosis of prostate cancer.; Castrate level of serum testosterone (<50 ng/mL) achieved by prior hormonal therapy consisting of either a) orchiectomy or b) luteinizing hormone-releasing hormone (LHRH) agonists with or without an anti-androgen; Castrate level of serum testosterone (<50 ng/mL) achieved by prior hormonal therapy consisting of either a) orchiectomy or b) luteinizing hormone-releasing hormone (LHRH) agonists with or without an anti-androgen; Lab requirements (Hematology):; White blood count (WBC) ≥3,000/mm3; Absolute neutrophil count ≥1,500/mm3; Platelet ≥100,000/ mm3; Hemoglobin ≥10 gm/d Lab requirements (Serum Chemistry): Bilirubin <1.5 X ULN (the upper limit of normal) (Subjects with confirmed Gilbert's Disease as the cause of their elevated bilirubin are to be permitted.); Serum alanine aminotransferase/serum aspartate aminotransferase (ALT/AST) < 2.5 X ULN (the upper limit of normal); Serum creatinine <1.5 X ULN(the upper limit of normal); Negative screen for Human Immunodeficiency virus (HIV), Hepatitis B virus (HBV) antigen, and Hepatitis C virus (HCV). If testing was done within the past three months, there is no need to repeat testing, as long as documentation of results is provided to the study site. Subjects must receive counseling and sign a separate informed consent for HIV testing.; Subjects and their partners of reproductive potential must agree to use an effective form of contraception during the period of drug administration and for four weeks following the completion of the last administration of the study drug. An effective form of contraception is defined as oral contraceptives plus one form of barrier method or double barrier methods (condom with spermicide or condom with diaphragm).; Subjects must be able to understand the potential risks and benefits of the study, and be able to read and give written informed consent. Exclusion Criteria: History of non-prostate, primary, malignant cancer, except for non-melanoma skin cancer within previous five years; History of splenectomy; Autoimmune- or Ab-mediated disease including, but not limited to, systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, temporal arteritis, and thyroiditis; Clinically significant cardiac disease (New York Heart Association Class III/IV) or severe debilitating pulmonary disease; Radiation therapy within four weeks prior to start of study treatment (Day -1); Patients may not have received more than one prior chemotherapy; The following medications within four weeks prior to start of study treatment (Week 1): systemically administered radiopharmaceuticals such as bone seeking isotopes (e.g., samarium-153 Lexidronam); hematopoietic growth factors other than erythropoietin; medroxyprogesterone as an appetite stimulant; or alternative medicine treatments for prostate cancer, including Prostasol (formerly: PC-Plus), saw palmetto, or Zyflamend®; Active central nervous system (CNS) or symptomatic epidural metastatic disease; An infection requiring antibiotic treatment within seven days of starting study treatment (Day -1); A requirement for daily systemic corticosteroids for any reason; or other immunosuppressive or immunomodulatory agents. Topical, nasal or physiologic corticosteroids are to be permitted.; Administration of live attenuated vaccines within eight weeks of start of study treatment (Day -1) and throughout the study; Administration of subunit or killed vaccines, such as influenza or pneumococcal vaccine, within two weeks prior to study treatment (Day-1) and throughout the study; EXCEPTION - Vaccination for influenza is permitted between Week 12 through Week 16 and after Week 20.; Positive stool guaiac, excluding hemorrhoids or documented radiation-induced proctitis if test is performed at the discretion of the treating physician (stool guaiac test is not required to screen for eligibility).; Any other medical condition that in the opinion of the Investigator may interfere with a subject's participation in, or compliance with, the study; Participation in a therapeutic research study or receipt of an investigational drug within 4 weeks leukapheresis.; Allergy to ganciclovir or acyclovir.
Sex/Gender	Sexes Eligible for Study: Male
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01140373
Other Study ID Numbers ICMJE	09-036
Has Data Monitoring Committee	Not Provided
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Memorial Sloan Kettering Cancer Center
Study Sponsor ICMJE	Memorial Sloan Kettering Cancer Center
Collaborators ICMJE	United States Department of Defense
Investigators ICMJE	Principal Investigator: Susan Slovin, MD, PhD Memorial Sloan Kettering Cancer Center
PRS Account	Memorial Sloan Kettering Cancer Center
Verification Date	November 2017
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP