Digestive System Diseases

All Conditions

Symptoms and General Pathology

Nervous System Diseases

Colonic Diseases

Pain

Visceral Pain

Intestinal Diseases

Gastrointestinal Diseases

Nociceptive Pain

Neurologic Manifestations

Analgesics

Central Nervous System Depressants

All Drugs and Chemicals

Gastrointestinal Agents

Herbal and Botanical

Analgesics, Opioid

Trimebutine

Hydrogen Sulfide

Parasympatholytics

Cola

GIC-1001 , 250 mg TID during 3 consecutive days + a last, 10th dose in the morning of Day 4 (colonoscopy day)

GIC-1001 , 375 mg TID during 3 consecutive days + a 10th dose in the morning of day 4 (colonoscopy day)

GIC-1001 , 500 mg TID during 3 consecutive days + a 10th dose in the morning of day 4 (colonoscopy day)

Placebo, TID during 3 consecutive days, + a 10 th dose in the morning of day 4 (colonoscopy day)

GIC-1001 oral tablet, white-coated, to be taken with water

GIC-1001

Mark V Larson, MD

Michael DeMicco, MD

Mark Lamet, MD

Taddese Desta, MD

Cynthia Schaeffer, MD

Vivek Gumaste, MD

Theadore Ptak, MD

Anand Sahai, MD

Umedchandra Shah, MD

Suryakanth R. Gurudu, MD

Robert Enns, MD

Narayanachar S Murali, MD

Vishal Gupta, MD

Albert Cohen, MD

Vitaly Fishbein, MD

Dennis Riff, MD

GIC-1001 is a novel, orally-administered, colonic analgesic drug developed as an alternative to i.v. sedation during full colonoscopy. It will be evaluated for efficacy and safety in a multi-center, randomized, double-blind, placebo controlled, dose-ranging, proof of concept Phase 2a trial. Up to 240 patients will receive one of 3 doses of GIC-1001 or its matching placebo. A pharmacokinetic evaluation will be carried out on a subset of patients (N: 24).

1. Study Objectives

   1.1 Primary objective: The primary objective of this Phase IIa study is to establish clinical Proof-of-Concept (POC) by providing clinically and statistically significant evidence that GIC-1001 is safe and effective in managing visceral pain in male and female patients who undergo sedation-free, full colonoscopy for preventive purposes.

   1.2 Secondary objectives: Secondary objectives will include the selection of the optimal dose of GIC-1001 from a safety/efficacy ratio point of view, establish a preliminary safety profile of the drug in patients, and obtain a preliminary general efficacy profile of GIC-1001 by assessing various secondary endpoints
2. Study Endpoints

   2.1 Primary endpoints:

   Visceral pain will be assessed using a 100-mm VAS, measured at various times and anatomical segments (N: 8) throughout the colon, i.e.:
   1. Prior to intra-rectal insertion of the endoscope;
   2. After insertion through the anus;
   3. After passage through the rectosigmoid segment;
   4. Immediately after passage through the splenic flexure;
   5. Immediately after passage through the hepatic flexure;
   6. Once the caecum is reached;
   7. Immediately after passage through the splenic flexure during scope withdrawal; and
   8. At the end of the procedure, once the colonoscope has been completely removed. Any additional episodes of pain experienced by the patient will also be assessed using the 100-mm VAS scale.

   The area under the curve (AUC) calculated from all serial measurements made will be used for statistical purposes, where the length of inserted colonoscope determines the VAS measurement's location.

   2.2 Secondary endpoints:
   1. Overall pain perception (100-mm VAS) at the end of the procedure;
   2. Time to reach the caecum with the endoscope (intubation time from rectum to caecum defined as time-to-caecum);
   3. Total examination time, defined at the time from introduction to removal of the colonoscope;
   4. Percentage of completed procedures;
   5. Endoscopist's perception of the adequacy of analgesia, difficulty of insertion, and amount of colonic spasm on insertion and withdrawal (five-point Likert scale);
   6. Use of rescue sedation (i.e. midazolam or midazolam followed by fentanyl)
   7. Safety as assessed by the incidence of treatment emergent adverse effects during the procedure and for 30 days after;
   8. Plasma determination of trimebutine and N-desmethyl-trimebutine moieties at GIC-1001 plasmatic steady state;
   9. Patient satisfaction with treatment (five-point Likert scale);
   10. Patient' willingness for repeat colonoscopy in the future (five-point Likert scale); and
   11. Safety of GIC-1001.
3. Study Design This is a randomized, double-blind, placebo-controlled parallel design 4-treatment arms study. Eligible patients will be randomized in a 1:1:1:2 ratio to one of 4 treatment arms: low (250 mg), mid (375 mg) or high (500 mg) dose of GIC-1001, or matching placebo. All potential study subjects will be screened and assessed for eligibility within maximum two (2) weeks prior to randomization. Bowel preparation will be performed using a polyethylene glycol (PEG) based regimen the night before the actual procedure.
4. Number of Clinical Sites: This trial will be conducted in both Canada and USA. Up to ten (10) clinical sites will participate in this trial. The lead Investigator for this trial is Dr Mark V. Larson MD, Head of Digestive Endoscopy, Mayo Clinic, Rochester MN, USA
5. Study population and sample size: Approximately 240 patients will be randomized in this study. Male and female patients having an indication for full colonoscopy, mainly for colorectal cancer screening and surveillance. Only naïve subjects, i.e. who never underwent colonoscopy before, will be eligible.
6. Inclusion Criteria See Eligibility Section
7. Exclusion Criteria See Eligibility Section
8. Study Drugs Administration and Schedule:

   GIC-1001, or its matching placebo will be administered as follows:
   1. One tablet TID on an empty stomach for three (3) consecutive days prior to colonoscopy.
   2. Last dose taken at the clinical site at least one (1) hour prior to beginning of procedure (endoscope insertion).
   3. Bowel preparation to be performed using PEG based regimen the day before the actual procedure.
   4. Three (3) different GIC-1001 dose levels will be studied:

      * 250 mg TID
      * 375 mg TID
      * 500 mg TID
      * Matching placebo TID
9. Concomitant Medications

   9.1 Prior to colonoscopy, the following medication will be permitted: Aspirin (ASA) at low levels for cardiovascular health, if dose and regimen stable for the last 6 months prior to colonoscopy.

   9.2 The following medications and foods will be prohibited:
   * Any prescription chronic analgesic narcotic, anti-spasmodic, anti-inflammatory medications are forbidden for 30 days prior to screening. (i.e. Washout ≥ 30 days)
   * Selective Serotonin Re-uptake Inhibitors (SSRIs) are forbidden for 30 days prior to screening, unless patient has been on a stable dose for 3 consecutive months prior to screening.
   * Over-the-counter analgesics, or anti-inflammatory medication, oral or topical used for acute pain treatment must be washed out for ≥ 7days prior to screening.
   * Acute or as needed prescription or non-prescription anti-inflammatory and/or analgesic treatment within one (1) week prior to colonoscopy.
   * Use of bowel stimulant laxatives, such bisacodyl, within one (1) week preceding randomization.
   * Use of antidiarrheic medication, such as diphenoxylate, loperamide, kaopectate or bismuth salts, within one (1) week preceding randomization.
   * Administration of barium enema within two (2) weeks preceding randomization.
   * Colonic irritant beverages or foods, such as caffeine-containing beverages (e.g. coffee, Coca-Cola), spices, as well as foods containing seeds (i.e. tomatoes, strawberries, kiwis, raspberries) within 24 hours preceding colonoscopy.
   * Use of any other investigational drug is prohibited unless discontinued, within at least 30 days prior to randomization.
   * Additionally, Prior and Concomitant Medications are to be recorded in the CRF starting 30 days prior to Screening Visit CLV1.
10. Efficacy Evaluation: Colonic analgesic clinical efficacy of GIC-1001 will be measured using a continuous, horizontal 100-mm VAS, at pre-determined times and colonic anatomical segments. At least 8 measurements will be done by the participating patients themselves (see Primary Endpoint section). Subjects will receive proper instructions on the use of the VAS prior to colonoscopy. Overall experience of visceral pain (if any) will be evaluated using the AUC constructed from all calculated VAS self-measurements for each patient. Additional, secondary, efficacy endpoints will also be measured, including time-to-caecum, colonoscopy completion rate and antispasmodic activity.
11. Safety Evaluation: Safety will be assessed using the performance of physical exams, ECG, various laboratory safety tests and the occurrence of adverse events. AEs will be mapped to MedDRA, version 16.
12. Sample Size Considerations: It has been reported in the medical literature that a MCID range of 10-15 mm on the 100-mm VAS is clinical significant in the evaluation of colonoscopy-related visceral pain. Using this value, with an alpha of 0.05 and a beta of 0.9, about 50 patients would be needed in each active arm considering a 90-patient placebo arm. Total study sample size is then estimated at approximately 240 randomized patients.
13. Statistical Analysis: The primary outcome measure will be the mean 100-mm VAS AUC in each treatment arm.

A Phase 2a, Proof-of-Concept Study of GIC-1001 in the Management of Visceral Pain During Sedation-Free, Full Colonoscopy

A Randomized, Double-Blind, Placebo-Controlled, Phase 2a Proof-of-Concept Study of GIC-1001 for the Management of Visceral Pain in Subjects Undergoing Sedation-Free, Full Colonoscopy

The Primary Outcomes Measure was the pain VAS 100-mm AUC (0mm = no pain; 100mm = worst pain), constructed from serial pain VAS measurements performed during colonoscopy. At least 8 pain VAS measurements were made, and the length of the colonoscope inserted (or removed on the way out) was recorded at every measurement. The X-axis of the VAS versus anatomical locations was defined accordingly: each VAS value corresponded to a relative length of inserted colonoscope (d/2Lc) of the X axis, where d was the actual length of the inserted colonoscope and 2Lc represented twice the total length of the colon examined (Lc). Before scope insertion the X value equaled zero. Once the caecum was reached, the X value was 0.5. Upon complete removal of the endoscope, the X value was 1. This allowed standardization of colonic length between study subjects. Visceral pain AUC (mm) was calculated from all serial measurements, where the length of inserted colonoscope determined the VAS measurement's location

Time to Caecum is the time taken by the physician to reach the caecum with the colonoscope, from the insertion in the anus. Time to Caecum was measured during colonoscopy, for which total duration of colonoscopy ranged between a minimum of 5.00 and a maximum of 50.10 minutes.

Qualitative outcome: colonoscopy completion is defined as a procedure performed entirely, from initial anal insertion, reaching of caecum, and complete removal of the scope. Completion rate is then the number of patient (%) with a complete colonoscopy (up to the caecum) divided by the number of trial participants.

A pharmacokinetic (PK) analysis was carried out on the first 24 patients randomized, equally distributed between treatment groups; 18 patients were assigned to active treatment

Defined as the time from endoscope insertion to complete removal of the endoscope; measured in minutes

Endoscopist's perception of the adequacy of analgesia, difficulty of insertion and withdrawal measured on a five-point Likert scale: Strongly Agree, Agree, Agree nor Disagree, Disagree, Strongly Disagree

Endoscopist's perception of the amount of colonic spasm on insertion and withdrawal measured on five-point Likert scale according to the following: Strongly Agree, Agree, Agree nor Disagree, Disagree, Strongly Disagree

Patients' willingness for repeat colonoscopy, was assessed with the Patient Willingness to Repeat Experience (P.W.R.E.) questionnaire (1 question), asking patients to rate their willingness to repeat the procedure according to a 5-point Likert scale: Strongly Agree, Agree, Agree nor Disagree, Disagree, Strongly Disagree. The P.W.R.E was administered after the colonoscopy during subject recovery.

Subject satisfaction and acceptability of the colonic analgesia modality offered by GIC-1001 was assessed with the Patient Global Impression of Abdominal Pain (P.G.I.A.P.) (1 question), asking patients to rate their pain during the procedure according to a 5-point Likert scale: Absent, Mild, Moderate, Severe, Intolerable. The P.G.I.A.P was administered after the colonoscopy during subject recovery.

JSS Medical Research Inc.

Algorithme Pharma Inc

gicare Pharma Inc.

Safety was assessed via performance of physical exams, vital signs, 12-lead ECG, laboratory safety tests (hematology, biochemistry and urinalysis) and the occurrence of adverse events.

GIC-1001 , 250 mg TID during 3 consecutive days + a last, 10th dose in the morning of Day 4 (colonoscopy day)

GIC-1001: GIC-1001 oral tablet, white-coated, to be taken with water

GIC-1001 Low Dose

GIC-1001 , 375 mg TID during 3 consecutive days + a 10th dose in the morning of day 4 (colonoscopy day)

GIC-1001: GIC-1001 oral tablet, white-coated, to be taken with water

GIC-1001 Mid-dose

GIC-1001 , 500 mg TID during 3 consecutive days + a 10th dose in the morning of day 4 (colonoscopy day)

GIC-1001: GIC-1001 oral tablet, white-coated, to be taken with water

GIC-1001 , High Dose

Placebo, TID during 3 consecutive days, + a 10 th dose in the morning of day 4 (colonoscopy day)

GIC-1001: GIC-1001 oral tablet, white-coated, to be taken with water

GIC-1001 Matching Placebo

Total

Age, Continuous

Sex: Female, Male

Asian/Oriental

Black

Caucasian

Hispanic

Other

Race/Ethnicity, Customized

Demographics provided for the Full Analysis Set (FAS; N=262), defined as all randomized patients who received at least one dose of study drug, had a baseline and at least one post-baseline VAS rating.

Patrick Colin

AUC Censored (Standardized)- PP Population

AUC- censorsed (standardized); FAS

AUC LOCF (standardized); FAS

AUC- censorsed (standardized); PP

AUC LOCF (standardized); PP

Primary endpoint assessed in the FAS (randomized patients who received at least one dose of study drug, had a baseline and at least one post-baseline VAS rating; N=262) and PP analysis sets (randomized patients in the FA population with ≥80% treatment compliance, who had at least 6/8 VAS ratings and no major protocol deviations; N=213)

Measurements of Visceral Pain, Using a 100-mm Visual Analog Scale (VAS)

FAS (randomized patients who received at least one dose of study drug, had a baseline and at least one post-baseline VAS rating; N=262)

Time to Caecum

Colonoscopy Completion Rate (%)

Plasma Concentration- Trimebutine

Plasma Concentration-N-Desmethyl-Trimebutine

Trimebutine and N-Desmethyl-Trimebutine plasma concentrations were assessed in all arms, with the exception of placebo

Safety-Plasma Concentrations of Trimebutine and N-Desmethyl-Trimebutine

Total Examination Time (Colonoscopy)

Adequate Analgesia

Difficult Insertion

Difficult Withdrawal

Endoscopist's Perception of Colonoscopy- Adequacy of Analgesia, Difficulty of Insertion and Withdrawal

Colonic Spasm insertion

Colonic Spasm WIthdrawal

Endoscopist's Perception of Colonoscopy- Amount of Colonic Spasm on Insertion and Withdrawal

Patient's Willingness to Repeat Experience

Subject Satisfaction and Acceptability of the Colonic Analgesia - Patient's Global Impression of Abdominal Pain

Overall Study

Neoplasms

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Lymphoma

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Lymphoma, Mantle-Cell

Lymphoma, Follicular

Lymphoma, B-Cell, Marginal Zone

Lymphoma, Non-Hodgkin

Lymphoma, B-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hematologic Diseases

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Lymphosarcoma

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Mantle Cell Lymphoma

Follicular Lymphoma

Marginal Zone Lymphoma

B-cell Lymphoma

Antineoplastic Agents

Antirheumatic Agents

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Bendamustine Hydrochloride

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Up to 12 patients will receive a single infusion of CAR.k.28. The starting dose will be 2.5x10\^5 cells/kg of each product. Up to 3 dose levels of CAR.k.28 cells will be tested with at least 3 patients enrolled at each dose cohort before dose escalation is considered based on the incidence of dose limiting toxicity (DLT). An expansion cohort will enroll up to 8 patients at the recommended phase 2 dose. Prior to receiving the infusions, patients will undergo lymphodepletion with fludarabine and bendamustine. Patients with a known history of intolerance to bendamustine may be considered for lymphodepletion with fludarabine and cyclophosphamide.

Three dose levels will be evaluated: Dose level 1 (5x10\^5 cells/kg), Dose level 2 (1x10\^6), and dose level 3 (2x10\^6 cells/kg).

CAR.k.28

500 mg/m\^2/day IV for 3 consecutive days

70 mg/m\^2/day administered over 3 consecutive days.

Bendamustine

Catherine Cheng

Kelly Hoye

Natalie Grover, MD

Paul Armistead

Anne Beaven, MD

James Coghill

Christopher Dittus, MD

Gianpietro Dotti

Paul Eldridge

Katarzyna Jamieson

Emily Kassam

Grace Park

Alicia Pinto

Marcie Riches

Barbara Savoldo

Jonathan Serody, MD

Thomas Shea, MD

Benjamin Vincent

Kimberly Wehner

William Wood

Ashley Zanter

This study will combine both T cells and antibodies in order to create a more effective treatment. The treatment tested in this study uses modified T-cells called Autologous T Lymphocyte Chimeric Antigen Receptor (ATLCAR) cells targeted against the kappa light chain antibody on cancer cells. For this study, the anti-kappa light chain antibody has been changed so instead of floating free in the blood, a part of it is now joined to the T cells. Only the part of the antibody that sticks to the lymphoma cells is attached to the T cells. When an antibody is joined to a T cell in this way, it is called a chimeric receptor. The kappa light chain chimeric (combination) receptor-activated T cells are called ATLCAR.κ.28 cells. These cells may be able to destroy lymphoma cancer cells. They do not, however, last very long in the body so their chances of fighting the cancer are unknown.

Previous studies have shown that a new gene can be put into T cells to increase their ability to recognize and kill cancer cells. A gene is a unit of DNA. Genes make up the chemical structure carrying your genetic information that may determine human characteristics (i.e., eye color, height and sex). The new gene that is put in the T cells in this study makes an antibody called an anti-kappa light chain. This anti-kappa light chain antibody usually floats around in the blood. The antibody can detect and stick to cancer cells called lymphoma cells because they have a substance on the outside of the cells called kappa light chains.

The purpose of this study is to determine whether receiving the ATLCAR.κ.28 cells is safe and tolerable and learn more about the side effects and how effective these cells are in fighting lymphoma. Initially, the study doctors will test different doses of the ATLCAR.κ.28, to see which dose is safer for use in lymphoma patients. Once a safe dose is identified, the study team will administer this dose to more patients, to learn about how these cells affect lymphoma cancer cells and identify other side effects they might have on the body.

This is the first time ATLCAR.κ.28 cells are given to patients with lymphoma. The Food and Drug Administration (FDA), has not approved giving ATLCAR.κ.28 as treatment for lymphoma. This is the first step in determining whether giving ATLCAR.κ.28 to others with lymphoma in the future will help them.

This study is a single center, open-label phase 1 clinical trial designed to determine the safety of escalating doses of autologous activated T lymphocytes (ATLs) expressing the chimeric antigen receptor specific for the kappa-light chain of human immunoglobulins (CAR.κ) in subjects with relapsed/refractory kappa-positive (κ+) mantle cell and indolent non-Hodgkin lymphomas (NHL). During dose finding, up to 12 subjects will receive a single infusion of ATL product expressing the CAR.κ encoding the CD28 co-stimulatory endodomain (CAR.κ.28). The starting dose will be 5.0 × 105 cells/kg. Up to 3 dose levels of CAR.κ.28 cells will be tested with at least 3 subjects enrolled in each dose cohort before dose escalation is considered based on the incidence of dose limiting toxicity (DLT). Prior to receiving the cell product, subjects will undergo lymphodepletion with fludarabine and bendamustine or cyclophophamide. Dose escalation will be guided by the modified 3+3 design. Any dose level may be expanded to 4-9 subjects to obtain more data at that dose or to include subjects for which insufficient cells are manufactured to enroll on their assigned higher dose level. If due to the expansion the estimated DLT rate at a dose is ≥0.33, the study would not escalate to the next highest dose level and the recommended phase 2 dose (RP2D) would be exceeded. If needed, an expansion cohort will enroll up to 8 subjects at the RP2D to further assess safety and efficacy of CAR.κ.28 cells. Secondary endpoints include evaluation of progression free survival (PFS), response rate (RR), duration of response (DoR) and overall survival (OS). The persistence of CAR.κ.28 cells in the peripheral blood will be assessed as an exploratory objective. The final RP2D including expansion data will be the dose with the DLT rate closest to 0.2.

The adoptive transfer of T cells targeting the kappa light chain (CAR.κ) is a promising treatment for patients with relapsed/refractory κ + NHL and has shown encouraging preclinical activity \[37\]. The CD8α stalk incorporated into CD28 signaling domain within the CAR, may improve the persistence of the CAR.κ T cells. Therefore, subjects in this study are being infused with this newly modified version of CAR.κ.28 so that persistence and efficacy will be improved compared to the older version of the CAR.κ molecule.

We hypothesize that CAR.κ.28 will be well tolerated in subjects with relapsed/refractory indolent and aggressive lymphomas positive for the kappa light chain and will show efficacy. We also anticipate that CAR.κ.28 will show fast expansion in the peripheral blood in the first 2 - 3 weeks, but also longer term persistence than the previous version of CAR.κ.28.

In this phase 1 single center study, peripheral blood will be collected for production of CAR.κ.28 cells prior to conditioning chemotherapy in subjects with relapsed/refractory κ+ indolent lymphoma including follicular lymphoma grade 1-3b, splenic marginal zone lymphoma, extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone lymphoma, and mantle cell lymphoma. During the approximately 1-2 months necessary for CAR-T cell production, subjects may undergo standard of care treatment ("bridging therapy") per physician's discretion. Subjects must sign consent forms before cells are procured and again prior to undergoing lymphodepleting chemotherapy and cellular treatment. At 2-14 days (preferably 2-4 days) after lymphodepletion with bendamustine and fludarabine, we will infuse the CAR.κ.28 cell product. Subjects in this study will receive CAR.κ.28 cell product in one of the three planned dose escalation cohorts. Dose levels of CAR.κ.28 cells administered will range between 5.0 × 105 cells/kg and 2 × 106 cells/kg. These doses have been evaluated in previous phase 1 studies of CAR-T cell lymphocytes \[37-39\] including a phase 1 trial targeting the kappa light chain on malignant B cells in which the construct included the CD28 co-stimulatory endodomain \[37\]. An expansion cohort will enroll up to 8 subjects at the RP2D to further assess safety and efficacy of CAR.κ.28 cells. In all subjects, we will measure the persistence of CAR.κ.28 cells in the peripheral blood at different time points by measuring the level of the transgene and by phenotypic analyses.

OUTLINE

Cell Procurement Peripheral blood, up to 300 mL (in up to 3 collections) will be obtained from subjects for cell procurement. In subjects with inadequate lymphocyte count in the peripheral blood, a leukapheresis may be performed to isolate sufficient T cells. The parameters for apheresis will be up to 2 blood volumes.

Lymphodepleting Regimen Subjects will receive a "pre-conditioning" cytoreductive regimen of bendamustine 70 mg/m2/day administered IV followed by fludarabine 30 mg/m2/day administered IV over 3 consecutive days. These agents will be administered per institutional guidelines. Prophylaxis (e.g., hydration, antiemetics, etc.) needed prior to fludarabine and bendamustine chemotherapy will be provided per institutional guidelines. At the discretion of the clinical investigator, subjects with a known history of intolerance to bendamustine may be considered for lymphodepletion with cyclophosphamide 500 mg/m2/day administered IV followed by an IV dose of fludarabine 30 mg/m2/day administered over 3 consecutive days. These agents will be administered per institutional guidelines.

Cell Administration The cellular product consisting of CAR.κ.28 cells will be administered by a licensed healthcare provider (oncology nurse or physician) via intravenous injection over 5 - 10 minutes through either a peripheral or a central line. The volume of infusion will depend upon the concentration of the cells when frozen and the size of the subject. The expected volume will be 1-50cc.

Post lymphodepletion, subjects who meet eligibility criteria for cellular therapy will receive CAR.κ.28 cells within 2 - 14 days, but preferably within 2-4 days, after completing the lymphodepleting chemotherapy regimen.

During dose finding, a single dose of CAR.κ.28 will be given after lymphodepletion. The cell dose levels that will be evaluated are outlined below.

Expansion Cohort, CAR.κ.28 will be given after lymphodepletion. Subjects will receive the RP2D.

Duration of Therapy

Therapy in LCCC1811-ATL involves a single cell infusion of CAR.K.28 cells. Treatment with at least one infusion will be administered unless:

* Subject decides to withdraw from study treatment, or
* General or specific changes in the subject's condition render the subject unacceptable for further treatment in the judgment of the investigator.

Duration of Follow-up Subjects will be followed for up to 15 years for RCR evaluation or until death, whichever occurs first. In addition to this follow-up, subjects removed from study treatment for unacceptable adverse events will be followed until resolution or stabilization of the adverse event.

Subjects who experience unequivocal disease progression and start alternate therapy after receiving a cell infusion still be required to complete abbreviated follow up procedures.

Study of Kappa Chimeric Antigen Receptor (CAR) T Lymphocytes Co-Expressing the Kappa and CD28 CARs for Relapsed/Refractory Kappa+ Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.

Phase 1 Study of the Administration of T Lymphocytes Expressing the Kappa Chimeric Antigen Receptor (CAR) and CD28 Endodomain for Relapsed/Refractory Kappa+ Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.

The duration of response will be defined as time from documentation of tumor response per Lugano criteria for Non-Hodgkin Lymphoma (NHL) or International Workshop on Chronic Lymphocytic Leukemia (IWCLL) for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL).

Toxicity is classified and graded using the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 5.0). Grade 1 Mild; asymptomatic or mild symptoms; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to Adverse Event (AE). Immune effector cell-associated neurotoxicity syndrome (ICANS) symptoms will be graded per American Society for Blood and Marrow Transplantation (ASBMT) ICANS Consensus Grading for Adults (scale from 1-mild to 4-critical) and cytokine release syndrome (CRS) symptoms will be graded according to ASBMT CRS Consensus Grading (a scale from 1-mild to 5-death).

PFS is defined from the date of administration of CAR.κ.28 infusion to progression, or death as a result of any cause per revised Lugano criteria for Non-Hodgkin Lymphoma (NHL) and International Workshop on Chronic Lymphocytic Leukemia (IWCLL) for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL).

Overall survival will be measured from the date of administration of CAR.κ.28 infusion to date of death

The objective response rate will be defined as the rate of complete responses (CR) + partial responses (PR) by 8 weeks post CAR.κ.28 infusion per revised Lugano criteria for Non-Hodgkin Lymphoma (NHL). For Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) patients, the rate of CR + PR will be defined by the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria by 8 weeks post-CAR.κ.28 infusion

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase 2a, Proof-of-Concept Study of GIC-1001 in the Management of Visceral Pain During Sedation-Free, Full Colonoscopy	NCT01926444	Pain Cancer Colonic Disease...	GIC-1001	40 Years - 70 Years	gicare Pharma Inc.
A Phase 2a, Proof-of-Concept Study of GIC-1001 in the Management of Visceral Pain During Sedation-Free, Full Colonoscopy	NCT01926444	Pain Cancer Colonic Disease...	GIC-1001	40 Years - 70 Years	gicare Pharma Inc.
Study of Kappa Chimeric Antigen Receptor (CAR) T Lymphocytes Co-Expressing the Kappa and CD28 CARs for Relapsed/Refractory Kappa+ Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.	NCT04223765	Mantle Cell Lym... Follicular Lymp... Splenic Margina... Extranodal Marg... Nodal Marginal ... Indolent Non-ho...	CAR.k.28 Fludarabine Cyclophosphamid... Bendamustine	18 Years -	UNC Lineberger Comprehensive Cancer Center

Spots Global Cancer Trial Database for kappa

Every month we try and update this database with for kappa cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for kappa

Every month we try and update this database with for kappa cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for kappa cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.