LMP-specific T-cells for Patients With Relapsed EBV-positive Lymphoma
ALCI
Administration of LMP-Specific Cytotoxic T-Lymphocytes to Patients With Relapsed EBV-Positive Lymphoma (ALCI) / Previously Known as: Administration of Neomycin Resistance Gene Marked LMP2A-Specific Cytotoxic T-Lymphocytes to Patents With Relapsed EBV-Positive Lymphoma (ALASCAR)
3 other identifiers
interventional
74
1 country
2
Brief Summary
This protocol is broken up into 2 portions to determine the maximum tolerated dose for treating patients with a type of lymph gland disease. The 1st portion, called ALASCER are for people with a type of lymph gland cancer called Hodgkin or non-Hodgkin Lymphoma or Lymphoepithelioma which has returned or may return or has not gone away after treatment, including the best treatment we know for Lymphoma. While the 2nd portion (ALCI) also includes Lymphoepithelioma, severe chronic active EBV (SCAEBC), and leiomyosarcoma. Some patients with Lymphoma show evidence of infection with the virus that causes infectious mononucleosis Epstein Barr virus (EBV) before or at the time of their diagnosis. EBV is found in the cancer cells of up to half the patients with Hodgkin's and non-Hodgkin Lymphoma, suggesting that it may play a role in causing Lymphoma. The cancer cells (in lymphoma) and some B cells (in SCAEBV) infected by EBV are able to hide from the body's immune system and escape destruction. Investigators want to see if special white blood cells, called T cells, that have been trained to kill EBV infected cells can survive in your blood and affect the tumor. The investigators have used this sort of therapy to treat a different type of cancer that occurs after bone marrow or solid organ transplant called post transplant lymphoma. In this type of cancer the tumor cells have 9 proteins made by EBV on their surface. The investigators grew T cells in the laboratory that recognized all 9 proteins and were able to successfully prevent and treat post transplant lymphoma. However in Hodgkin disease and non-Hodgkin Lymphoma and SCAEBV, the tumor cells and B cells only express 2 EBV proteins. In a previous study we made T cells that recognized all 9 proteins and gave them to patients with Hodgkin disease. Some patients had a partial response to this therapy but no patients had a complete response. Investigators think one reason may be that many of the T cells reacted with proteins that were not on the tumor cells. In this present study we are trying to find out if we can improve this treatment by growing T cells that only recognize one of the proteins expressed on infected EBV Lymphoma cells called LMP-2a, and B cells called LMP1 and LMP2. These special T cells are called LMP specific cytotoxic T-lymphocytes (CTLs). The purpose of the study is to find the largest safe dose of LMP specific cytotoxic T cells, to learn what the side effects are and to see whether this therapy might help patients with Hodgkin disease, non-Hodgkin Lymphoma, Lymphoepithelioma, SCAEBV or leiomyosarcoma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Sep 2003
Longer than P75 for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 17, 2003
CompletedFirst Posted
Study publicly available on registry
June 18, 2003
CompletedStudy Start
First participant enrolled
September 1, 2003
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2014
CompletedResults Posted
Study results publicly available
February 7, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2020
CompletedJune 9, 2020
May 1, 2020
10.6 years
June 17, 2003
January 15, 2020
May 26, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Dose Limiting Toxicity (DLT) Rate by the NCI Common Toxicity Criteria (CTCAE) v2.0 and the Method of Przepiorka et al (Protocol Appendix I)
Dose limiting toxicity (DLT) rate is the proportion of participants with DLT. DLT will be defined as any toxicity that is irreversible, life threatening or Grade 3-4 considered to be primarily related to the LMP-specific cytotoxic T-lymphocytes (CTL) injection or development of Grade III-IV Graft versus host disease (GVHD). Toxicity will be evaluated according to the CTCAE Version 2.0. GVHD will be graded by the method of Przepiorka et al (protocol Appendix I).
6 weeks post second CLT infusion
Secondary Outcomes (2)
Response Rate According to the Harmonization Project (Protocol 8.5.1) or RECIST Criteria.
Up to 4 months after the last infusion
Grade III-IV Toxicity Rate in Participants Receiving an Extended Dosage Regimen According to the NCI Common Toxicity Criteria (CTCAE) Version 2.0 and the Method of Przepiorka et. al. (Protocol Appendix I).
6 weeks after the final injection
Study Arms (9)
LMP1/2 CTLs (ALCI - Group A)
EXPERIMENTALPatients receiving CTLs as therapy for relapsed Lymphoma/Lymphoepithelioma/leiomyosarcoma or who are at risk for relapse
LMP1/2 CTLs (ALCI - Group B)
EXPERIMENTALPatients receiving CTLs as adjunctive therapy following autologous or syngeneic transplant.
LMP1/2 CTLs (ALCI - Group C)
EXPERIMENTALPatients receiving CTLs following allogeneic stem cell transplant.
LMP2A CTLs (ALASCER - Group A)
EXPERIMENTALPatients receiving CTLs as therapy for relapsed Lymphoma/Lymphoepithelioma/leiomyosarcoma or who are at risk for relapse
LMP2A CTLs (ALASCER - Group B)
EXPERIMENTALPatients receiving CTLs as adjunctive therapy following autologous or syngeneic transplant
LMP2A CTLs (ALASCER - Group C)
EXPERIMENTALPatients receiving CTLs following allogeneic stem cell transplant
LMP1/2 CTLs (ALCI - Expansion Group A)
EXPERIMENTALPatients receiving CTLs as therapy for relapsed Lymphoma/Lymphoepithelioma/leiomyosarcoma or who are at risk for relapse
LMP1/2 CTLs (ALCI - Expansion Group B)
EXPERIMENTALPatients receiving CTLs as adjunctive therapy following autologous or syngeneic transplant.
LMP1/2 CTLs (ALCI - Expansion Group C)
EXPERIMENTALPatients receiving CTLs following allogeneic stem cell transplant.
Interventions
Each patient will receive 2 injections, 14 days apart, according to the following dosing schedules: Dose Level One Day 0: 2 x 10\^7 cells/m2; Day 14: 2 x 10\^7 cells/m2 Dose Level Two Day 0: 2x10\^7 cells/m2; Day 14: 1x10\^8 cells/m2 Dose Level Three Day 0: 1x10\^8 cells/m2; Day 14: 2x10\^8 cells/m2
Each patient will receive 2 injections, 14 days apart, according to the following dosing schedules: Dose Level One Day 0: 2x10\^7 cells/m2; Day 14: 2x10\^7 cells/m2 Dose Level Two Day 0: 2x10\^7 cells/m2; Day 14: 1x10\^8 cells/m2 Dose Level Three Day 0: 1x10\^8 cells/m2; Day 14: 2x10\^8 cells/m2
Each patient will receive 2 injections, 14 days apart, according to the following dosing schedules: Dose Level One Day 0: 2x10\^7 cells/m2; Day 14: 2x10\^7 cells/m2 Dose Level Two Day 0: 2x10\^7 cells/m2; Day 14: 1x10\^8 cells/m2 Dose Level Three Day 0: 1x10\^8 cells/m2; Day 14: 2x10\^8 cells/m2
Each patient will receive 2 injections, 14 days apart, according to the following dosing schedules: Dose Level One Day 0: 2 x 10\^7 cells/m2; Day 14: 2 x 10\^7 cells/m2 Dose Level Two Day 0: 2x10\^7 cells/m2; Day 14: 1x10\^8 cells/m2 Dose Level Three Day 0: 1x10\^8 cells/m2; Day 14: 2x10\^8 cells/m2
Each patient will receive 2 injections, 14 days apart, according to the following dosing schedules: Dose Level One Day 0: 2x10\^7 cells/m2; Day 14: 2x10\^7 cells/m2 Dose Level Two Day 0: 2x10\^7 cells/m2; Day 14: 1x10\^8 cells/m2 Dose Level Three Day 0: 1x10\^8 cells/m2; Day 14: 2x10\^8 cells/m2
Each patient will receive 2 injections, 14 days apart, according to the following dosing schedules: Dose Level One Day 0: 2x10\^7 cells/m2; Day 14: 2x10\^7 cells/m2 Dose Level Two Day 0: 2x10\^7 cells/m2; Day 14: 1x10\^8 cells/m2 Dose Level Three Day 0: 1x10\^8 cells/m2; Day 14: 2x10\^8 cells/m2
Each patient will receive 2 injections, 14 days apart, according to the following dosing schedules: Dose Level One Day 0: 2 x 10\^7 cells/m2; Day 14: 2 x 10\^7 cells/m2
Each patient will receive 2 injections, 14 days apart, according to the following dosing schedules: Dose Level One Day 0: 2x10\^7 cells/m2; Day 14: 2x10\^7 cells/m2
Each patient will receive 2 injections, 14 days apart, according to the following dosing schedules: Dose Level One Day 0: 2x10\^7 cells/m2; Day 14: 2x10\^7 cells/m2
Eligibility Criteria
You may qualify if:
- Any patient, regardless of age or sex, with EBV-positive Lymphoma, or lymphoepithelioma regardless of the histological subtype or EBV (associated)-T/NK-LPD.
- In second or subsequent relapse (or first relapse or with active disease if immunosuppressive chemotherapy contraindicated or multiply relapsed patients in remission who have a high risk of relapse) OR any patient with primary disease or in first remission if immunosuppressive chemotherapy is contraindicated, e.g. patients who develop Hodgkin disease after solid organ transplantation or if the Lymphoma is a second malignancy e.g. a Richters transformation of CLL. (Group A) OR In remission or with minimal residual disease status after autologous or syngeneic SCT for Hodgkin's or non-Hodgkin's Lymphoma or lymphoepithelioma. (Group B) OR In remission or with detectable disease after allogeneic SCT. (Group C)
- Patients with life expectancy \> 6 weeks.
- Patients with a Karnofsky/Lansky score of \> 50
- No severe intercurrent infection.
- Donor HIV negative (if autologous product - patient must be HIV negative)
- No evidence of GVHD \> Grade II at time of enrollment.
- If post allogeneic SCT must not have less than 50% donor chimerism in either peripheral blood or bone marrow
- Patient, parent/guardian able to give informed consent.
- Patients with bilirubin \<3x normal, AST \<5x normal, and Hgb \>8.0 (see Section 7.2).
- Patients with a creatinine \<2x normal for age
- Patients should have been off other investigational therapy for one month prior to entry in this study.
You may not qualify if:
- Patients with a life expectancy of \<6 weeks.
- Patients with a Karnofsky/Lansky score of \< 50.
- Patients with a severe intercurrent infection.
- Patients with bilirubin \>3x normal. AST \>5x normal or abnormal prothrombin time.
- Patients with a creatinine \>2x normal for age
- Donors who are HIV positive (Patients who are HIV positive - if autologous product)
- Patients with GVHD Grades III-IV
- Due to unknown effects of this therapy on a fetus, pregnant women are excluded from this research. The male partner should use a condom.
- Note: Patients who would be excluded from the protocol strictly for laboratory abnormalities can be included at the investigator's discretion after approval by the CCGT Protocol Review Committee and the FDA reviewer.
- ALCI and ALCI Expansion (Part 2 of Study)
- Any patient, regardless of age or sex, with EBV-positive Hodgkin's or non-Hodgkin's Lymphoma, or lymphoepithelioma or leiomyosarcoma regardless of the histological subtype or EBV (associated)-T/NK-lymphoproliferative disease or Severe Chronic EBV#
- (#SCAEBV is defined as patients with high EBV viral load in plasma or PBMC (\>4000 genomes per ug PBMC DNA) and/or biopsy tissue positive for EBV)
- a - In second or subsequent relapse (or first relapse or with active disease if immunosuppressive chemotherapy contraindicated or multiply relapsed patients currently in remission who have a high risk of relapse) OR with primary disease or in first or subsequent remission if immunosuppressive chemotherapy is contraindicated, e.g. patients who develop Hodgkin disease after solid organ transplantation or if the Lymphoma is a second malignancy e.g. a Richters transformation of CLL.(Group A)
- b - In remission or with minimal residual disease status after autologous or syngeneic SCT for Hodgkin's or non-Hodgkin's Lymphoma/Lymphoepithelioma/SCAEBV. (Group B)
- c - Patients in remission or with detectable disease after allogeneic SCT. (Group C)
- +13 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
Texas Children's Hospital
Houston, Texas, 77030, United States
The Methodist Hospital
Houston, Texas, 77030, United States
Related Publications (5)
McLaughlin LP, Rouce R, Gottschalk S, Torrano V, Carrum G, Wu MF, Hoq F, Grilley B, Marcogliese AM, Hanley PJ, Gee AP, Brenner MK, Rooney CM, Heslop HE, Bollard CM. EBV/LMP-specific T cells maintain remissions of T- and B-cell EBV lymphomas after allogeneic bone marrow transplantation. Blood. 2018 Nov 29;132(22):2351-2361. doi: 10.1182/blood-2018-07-863654. Epub 2018 Sep 27.
PMID: 30262660DERIVEDBollard CM, Gottschalk S, Torrano V, Diouf O, Ku S, Hazrat Y, Carrum G, Ramos C, Fayad L, Shpall EJ, Pro B, Liu H, Wu MF, Lee D, Sheehan AM, Zu Y, Gee AP, Brenner MK, Heslop HE, Rooney CM. Sustained complete responses in patients with lymphoma receiving autologous cytotoxic T lymphocytes targeting Epstein-Barr virus latent membrane proteins. J Clin Oncol. 2014 Mar 10;32(8):798-808. doi: 10.1200/JCO.2013.51.5304. Epub 2013 Dec 16.
PMID: 24344220DERIVEDCohen JI, Jaffe ES, Dale JK, Pittaluga S, Heslop HE, Rooney CM, Gottschalk S, Bollard CM, Rao VK, Marques A, Burbelo PD, Turk SP, Fulton R, Wayne AS, Little RF, Cairo MS, El-Mallawany NK, Fowler D, Sportes C, Bishop MR, Wilson W, Straus SE. Characterization and treatment of chronic active Epstein-Barr virus disease: a 28-year experience in the United States. Blood. 2011 Jun 2;117(22):5835-49. doi: 10.1182/blood-2010-11-316745. Epub 2011 Mar 31.
PMID: 21454450DERIVEDFox CP, Haigh TA, Taylor GS, Long HM, Lee SP, Shannon-Lowe C, O'Connor S, Bollard CM, Iqbal J, Chan WC, Rickinson AB, Bell AI, Rowe M. A novel latent membrane 2 transcript expressed in Epstein-Barr virus-positive NK- and T-cell lymphoproliferative disease encodes a target for cellular immunotherapy. Blood. 2010 Nov 11;116(19):3695-704. doi: 10.1182/blood-2010-06-292268. Epub 2010 Jul 29.
PMID: 20671118DERIVEDBollard CM, Gottschalk S, Leen AM, Weiss H, Straathof KC, Carrum G, Khalil M, Wu MF, Huls MH, Chang CC, Gresik MV, Gee AP, Brenner MK, Rooney CM, Heslop HE. Complete responses of relapsed lymphoma following genetic modification of tumor-antigen presenting cells and T-lymphocyte transfer. Blood. 2007 Oct 15;110(8):2838-45. doi: 10.1182/blood-2007-05-091280. Epub 2007 Jul 3.
PMID: 17609424DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Helen E. Heslop
- Organization
- Baylor College of Medicine
Study Officials
- PRINCIPAL INVESTIGATOR
Helen E Heslop, MD
Center for Cell and Gene Therapy, Baylor College of Medicine
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor
Study Record Dates
First Submitted
June 17, 2003
First Posted
June 18, 2003
Study Start
September 1, 2003
Primary Completion
April 1, 2014
Study Completion
April 1, 2020
Last Updated
June 9, 2020
Results First Posted
February 7, 2020
Record last verified: 2020-05