LeukemiaPhase 1NCT00871702
Infusion of Genetically Modified T Cell for Post Transplant Patients With Relapsed Disease
A Phase 1 study testing CD34-TK75 transduced donor lymphocytes and Sub Study - 18 FHBG PET/CT Scans in people with Leukemia and Lymphoma, Non-Hodgkin, run by Washington University School of Medicine at 1 site in United States.
Trial summary
Primary Objective: To determine if there is significant toxicity associated with the administration of CD34-TK75 transduced donor lymphocytes after allogeneic BMT for relapsed hematologic malignancies Secondary Objectives: To determine if the patient develops any evidence of anti-leukemic effect from the… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia, Lymphoma, Non-Hodgkin, Hodgkin Disease
- What is being tested?
- CD34-TK75 transduced donor lymphocytes and Sub Study - 18 FHBG PET/CT Scans
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2010to Nov 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must be prior recipients of allogeneic BMT (matched 6/6 or 5/6 according to the National Marrow Donor Program) for any hematologic malignancy. Eligible patients would include those with leukemia, non Hodgkins Lymphoma, Hodgkins Disease, myelodysplastic syndrome and multiple myeloma.
- Patients must have laboratory, histologic, or cytogenetic evidence of disease relapse after allogeneic BMT.
- Patients may not have received prior therapy with transduced or non-transduced donor lymphocytes.
- Patients ≥ 18 years of age.
- The minimum number of transduced and purified lymphocytes from the same donor of donated cells for allogeneic transplant is is 1x105 per kg for all patients.
- Expected survival of patient is at least 4 weeks.
Show all 25Show fewer
- Required baseline organ function within 14 days prior to study entry:
- Renal function with creatinine less than 5 mg/dl.
- Liver function with SGOT, SGPT and alkaline phosphatase ≤ 4 times the upper limit of institutional normal.
- Bilirubin ≤ 5.0 mg/dl.
- Patient must have signed the informed consent prior to entry and express willingness to meet all the expected requirements of the protocol for the duration of the study.
- ECOG Performance Status ≤ 2
- All patients must agree to a repeat bone marrow, liver, gastro-intestinal or skin biopsies dependent on clinical course.
- Women of child bearing potential must have a negative pregnancy test (ß-HCG ) within 7 days of study entry.
- In addition patients # 3 to 8:
- Must have consented to participation in HRPO 09-0744, "Infusion of Genetically Modified T cells: A Pilot I Study of Tracking and Toxicity
- Must be willing to undergo 18FHBG-PET/CT-imaging
- Must be able to tolerate 45-60 minutes of imaging at each imaging timepoint.
- Women of child bearing potential must have an additional negative high sensitivity pregnancy test (20mlU ß-HCG /ml urine as administered in the Center for Clinical Imaging Research, Mallinckrodt Institute of Radiology, Washington University) prior to each imaging session (i.e. at days 10-16 and days 27-33).
- Must be the original donor for the allogeneic bone marrow transplant patient.
- No underlying conditions which would contra-indicate apheresis.
- Must have signed the informed consent and express willingness to meet all the expected requirements stated in the protocol for the duration of the study.
- Must be eligible according to Washington University "Guidelines for Eligibility of Normal Donors"
- Donors ≥ 18 years of age.
- Female donors of childbearing potential must have a confirmed negative pregnancy test.
Who cannot join
- Patients receiving immunosuppression (cyclosporin, FK506, prednisone, cellcept, methylprednisolone) for GvHD or other reasons at the time of lymphocyte infusion.
- Patients must not have evidence of active CMV or other active viral infection requiring antiviral therapy. A culture or PCR of blood for CMV must be negative for enrollment.
- Pregnant or lactating females.Note that a second and third high sensitivity pregnancy test (20mlU ß-HCG /ml urine as administered in the Center for Clinical Imaging Research, Mallinckrodt Institute of Radiology, Washington University) are required prior to each imaging session (i.e. at days 10-16 and days 27-33 for patients #3 to 8).
- Uncontrolled infection: Any uncontrolled viral, bacterial, or fungal infection.
- HIV infection.
- Acute medical problems such as ischemic heart or lung disease.
Show all 19Show fewer
- Patients with any underlying conditions which would contra-indicate therapy with study treatment (or allergies to reagents used in this study).
- Patients who have received atgam, campath [alemtuzumab] or daclizumab within 4 weeks of DLI.
- Patients receiving investigational drugs or treatments within 30 days of enrollment.
- Patients with tetracycline, penicillin, or streptomycin sensitivity.
- Patients with signs of acute GVHD as defined by the International Bone Marrow Transplant Registry (IBMTR) Severity Index for Acute Graft versus Host Disease (Rowlings, et al., Brit. J. Haematol. 97:855-64 [1997]). In addition patients may be excluded at the discretion of the treating physician.
- In addition for patients # 3 to 8 who will be imaged , exclude:
- Patients who are claustrophobic.
- Patients who are unable to tolerate 30-45 minutes of imaging.
- -Pregnant female donors
- Concomitant Medication and Treatment:
- -The principal investigator or a designated co-investigator at the respective institution must approve use of chemotherapeutic, antiviral or immunosuppressive medications.
- Medications and Treatments Not Allowed:
- -No other forms of chemotherapy will be administered after cell infusion during the treatment protocol.
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: Infusion of Genetically Modified T Cells: A Pilot Study of Tracking and Toxicity
Primary Objective:
- To determine if there is significant toxicity associated with the administration of CD34-TK75 transduced donor lymphocytes after allogeneic BMT for relapsed hematologic malignancies
Read more
Secondary Objectives:
- To determine if the patient develops any evidence of anti-leukemic effect from the administration of CD34-TK75 transduced donor lymphocytes
- To determine if ganciclovir administration to patients who develop Graft versus Host Disease (GVHD)results in clinical improvement after infusions of CD34-TK75 transduced lymphocytes.
Sub-Study Objective
The primary purpose is to perform PET imaging of CD34-TK transduced allogeneic donor T cells in patients who have relapsed hematologic malignancies after allogeneic hematopoietic stem cell transplantation (SCT). At this time the limited amount of cGMP quality virus produced by the NGVL will likely permit the imaging of only 3 patients. Consequently our current objective will be to establish that the TK-expressing cells can be detected by 18FHBG-PET in patient organs relevant for performing additional studies that are currently in the planning stages and for which we are working to produce additional virus.
The ultimate objective will be to use the TK substrate 18FHBG to locate the donor T cells within the recipient as they exert anti-leukemic effects, and the T cells can then be eliminated in response to in vivo administration of ganciclovir, before morbidity and mortality from GvHD occurs. We will use the imaging strategy to define patterns of T cell trafficking in humans pre and post-DLI infusion, and to determine where the cells reside while they mediate GVL in contrast to GvHD. We expect to obtain in vivo PET imaging markers predictive of GvHD before clinical symptoms occur.
Read the detailed description
This is a phase I study of to determine the safety of the administration of lymphocytes, collected from the bone marrow donor. Donor lymphocytes are often administered in the case of a relapsed cancer after allogeneic bone marrow transplantation, in the hope to reduce the amount or size of the relapsed cancer. In this study, we will look for a decrease of the size of the relapsed cancer.
By inserting genetic material (DNA) into the cells (lymphocytes) collected from the donor, these cells will be genetically modified and made very sensitive to the killing effects of a drug called ganciclovir, routinely used in the clinic after bone marrow transplantation to treat virus infections in transplant patients.
This research study is to determine, if administration of the drug ganciclovir to the recipient, after intravenous infusion of the genetically modified cells (lymphocytes) into the recipient, will reduce or even eliminate a life threatening complication of allogeneic transplantation, called graft versus host disease (GvHD). The drug ganciclovir will kill the infused genetically modified donor cells (lymphocytes) so they cannot cause GvHD.
In summary, the overall purpose of this research study is to determine, if administration of a seven day course of the drug ganciclovir to the donor lymphocyte recipient will either decrease the severity of GvHD, or will decrease the number of cases with life-threatening GvHD after donor lymphocyte infusions.
This study will also determine if insertion of a small piece of DNA (a small piece of genetic material), makes these donor lymphocytes opened up and sensitive to the killing effects of the drug ganciclovir, but at the same time does not harm the lymphocytes' ability to reduce the amount or size of the cancer in the recipient. The DNA to be inserted into the donor lymphocytes is transported into these cells by a type of virus called "retrovirus vector". This retrovirus vector is made so the virus cannot divide (cannot make more of itself), and cannot make cells or the recipient sick. Retroviruses do, however, allow for the gene (DNA) they are carrying, to be permanently inserted into the genetic material of the donor lymphocytes. Therefore, this inserted DNA will persist in the donor lymphocytes for the life of the lymphocytes.
Finally, this study will also determine if the administration of genetically manipulated donor lymphocytes is well tolerated.
Sub Study
The goal of this subproject is to see if an imaging procedure called 18FHBG-PET/CT can help us see if the lymphocytes you received have gone to the sites in the body where the anti-cancer effects are taking place.
- Conditions
- Leukemia, Lymphoma, Non-Hodgkin, Hodgkin Disease, Myelodysplastic Syndromes, Multiple Myeloma
- Being tested
- CD34-TK75 transduced donor lymphocytes, Sub Study - 18 FHBG PET/CT Scans
- Keywords
- Leukemia, Lymphoma, Non-Hodgkin, Hodgkin Disease, Myelodysplastic Syndromes, Multiple Myeloma
- Medical subject headings
- Leukemia, Lymphoma, Non-Hodgkin, Hodgkin Disease, Myelodysplastic Syndromes, Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD34-TK75 transduced donor lymphocytesGenetic
Sub Study - 18 FHBG PET/CT ScansRadiation
Three 18 FHBG PET/CT Scans will be performed first one at pre-DLI infusion, second 14 days post-DLI infusion and third 30 days post-DLI infusion - patients #3 - #8
| Study group | Role | What they receive |
|---|---|---|
| Donor lymphocyte infusion | Experimental | CD34-TK75 transduced T lymphocytes from donors matched at a 5/6 or 6/6 antigen level at a dose of 1.0 x 105 cells/kg recipient weight. Receives: Genetic: CD34-TK75 transduced donor lymphocytes; Radiation: Sub Study - 18 FHBG PET/CT Scans |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine if there is significant toxicity associated with the administration of CD34-TK75 transduced donor lymphocytes after allogeneic BMT for relapsed hematologic malignancies
Occurrence of grade 3-5 toxicity
72 hour infusional toxicity
Acute GVHD
Measured: Day 0 through Day 100
Perform PET imaging to allow us to locate the donor T cells within the recipient as they exert anti-leukemic effects, and the T cells can then be eliminated in response to administration of ganciclovir, before morbidity and mortality from GvHD occurs
Measured: Baseline, Day 14, and Day 30
To determine if there is significant toxicity associated with the administration of CD34-TK75 transduced donor lymphocytes after allogeneic BMT for relapsed hematologic malignancies
Occurrence of grade 3-5 toxicity
Measured: Day 100 - Year 15
Secondary outcomes (2)
To determine if the patient develops any evidence of anti-leukemic effect from the administration of CD34-TK75 transduced donor lymphocytes
Measured: 100 days
To determine if GCV administration to patients who develop GvHD results in clinical improvement after infusions of CD34-TK75 transduced lymphocytes.
Measured: 100 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2009 (estimated)
- Study startOct 2010
- Primary completionNov 2012
- Study completionNov 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (17)Papers the sponsor has linked to this study.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- John F. DiPersio, M.D., Ph.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00871702
- Sponsor's protocol ID
- 09-0744 / 201103095
- Status last verified
- Jul 2013
- First submitted
- 27 Mar 2009
- Last updated
- 11 Jul 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Rettig MP, Ritchey JK, Meyerrose TE, Haug JS, DiPersio JF. Transduction and selection of human T cells with novel CD34/thymidine kinase chimeric suicide genes for the treatment of graft-versus-host disease. Mol Ther. 2003 Jul;8(1):29-41. doi: 10.1016/s1525-0016(03)00142-4.
PubMed 12842426Rettig MP, Ritchey JK, Prior JL, Haug JS, Piwnica-Worms D, DiPersio JF. Kinetics of in vivo elimination of suicide gene-expressing T cells affects engraftment, graft-versus-host disease, and graft-versus-leukemia after allogeneic bone marrow transplantation. J Immunol. 2004 Sep 15;173(6):3620-30. doi: 10.4049/jimmunol.173.6.3620.
PubMed 15356106Drobyski WR, Keever CA, Roth MS, Koethe S, Hanson G, McFadden P, Gottschall JL, Ash RC, van Tuinen P, Horowitz MM, et al. Salvage immunotherapy using donor leukocyte infusions as treatment for relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation: efficacy and toxicity of a defined T-cell dose. Blood. 1993 Oct 15;82(8):2310-8.
PubMed 8400284Moolten FL. Tumor chemosensitivity conferred by inserted herpes thymidine kinase genes: paradigm for a prospective cancer control strategy. Cancer Res. 1986 Oct;46(10):5276-81.
PubMed 3019523Moolten FL, Wells JM. Curability of tumors bearing herpes thymidine kinase genes transferred by retroviral vectors. J Natl Cancer Inst. 1990 Feb 21;82(4):297-300. doi: 10.1093/jnci/82.4.297.
PubMed 2299679Miller AD, Buttimore C. Redesign of retrovirus packaging cell lines to avoid recombination leading to helper virus production. Mol Cell Biol. 1986 Aug;6(8):2895-902. doi: 10.1128/mcb.6.8.2895-2902.1986.
PubMed 3785217Kasid A, Morecki S, Aebersold P, Cornetta K, Culver K, Freeman S, Director E, Lotze MT, Blaese RM, Anderson WF, et al. Human gene transfer: characterization of human tumor-infiltrating lymphocytes as vehicles for retroviral-mediated gene transfer in man. Proc Natl Acad Sci U S A. 1990 Jan;87(1):473-7. doi: 10.1073/pnas.87.1.473.
PubMed 2404283Tiberghien P, Reynolds CW, Keller J, Spence S, Deschaseaux M, Certoux JM, Contassot E, Murphy WJ, Lyons R, Chiang Y, et al. Ganciclovir treatment of herpes simplex thymidine kinase-transduced primary T lymphocytes: an approach for specific in vivo donor T-cell depletion after bone marrow transplantation? Blood. 1994 Aug 15;84(4):1333-41.
PubMed 8049449Bordignon C, Bonini C, Verzeletti S, Nobili N, Maggioni D, Traversari C, Giavazzi R, Servida P, Zappone E, Benazzi E, et al. Transfer of the HSV-tk gene into donor peripheral blood lymphocytes for in vivo modulation of donor anti-tumor immunity after allogeneic bone marrow transplantation. Hum Gene Ther. 1995 Jun;6(6):813-9. doi: 10.1089/hum.1995.6.6-813.
PubMed 7548281Tiberghien P, Ferrand C, Lioure B, Milpied N, Angonin R, Deconinck E, Certoux JM, Robinet E, Saas P, Petracca B, Juttner C, Reynolds CW, Longo DL, Herve P, Cahn JY. Administration of herpes simplex-thymidine kinase-expressing donor T cells with a T-cell-depleted allogeneic marrow graft. Blood. 2001 Jan 1;97(1):63-72. doi: 10.1182/blood.v97.1.63.
PubMed 11133743Black ME, Newcomb TG, Wilson HM, Loeb LA. Creation of drug-specific herpes simplex virus type 1 thymidine kinase mutants for gene therapy. Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3525-9. doi: 10.1073/pnas.93.8.3525.
PubMed 8622970Szer J, Grigg AP, Phillips GL, Sheridan WP. Donor leucocyte infusions after chemotherapy for patients relapsing with acute leukaemia following allogeneic BMT. Bone Marrow Transplant. 1993 Feb;11(2):109-11.
PubMed 8435660Bar BM, Schattenberg A, Mensink EJ, Geurts Van Kessel A, Smetsers TF, Knops GH, Linders EH, De Witte T. Donor leukocyte infusions for chronic myeloid leukemia relapsed after allogeneic bone marrow transplantation. J Clin Oncol. 1993 Mar;11(3):513-9. doi: 10.1200/JCO.1993.11.3.513.
PubMed 8445426Kolb HJ, de Witte T, Mittermuller J, et al. (1993) Graft-versus-leukemia effect of donor buffy coat transfusions on recurrent leukemia after marrow transplantation. Blood 82: 214A
Kolb HJ, Schattenberg A, Goldman JM, Hertenstein B, Jacobsen N, Arcese W, Ljungman P, Ferrant A, Verdonck L, Niederwieser D, van Rhee F, Mittermueller J, de Witte T, Holler E, Ansari H; European Group for Blood and Marrow Transplantation Working Party Chronic Leukemia. Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients. Blood. 1995 Sep 1;86(5):2041-50.
PubMed 7655033
Study at a glance
From the registry record, last updated by the sponsor on 11 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Infusion of Genetically Modified T Cells: A Pilot Study of Tracking and Toxicity
- ClinicalTrials.gov ID
- NCT00871702
- Acronym / sponsor ID
- 09-0744 / 201103095
- Conditions
- Leukemia, Lymphoma, Non-Hodgkin, Hodgkin Disease, Myelodysplastic Syndromes, Multiple Myeloma
- Keywords
- Leukemia, Lymphoma, Non-Hodgkin, Hodgkin Disease, Myelodysplastic Syndromes, Multiple Myeloma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- Oct 2010
- Primary completion
- Nov 2012 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 30 Mar 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary Objective:
- To determine if there is significant toxicity associated with the administration of CD34-TK75 transduced donor lymphocytes after allogeneic BMT for relapsed hematologic malignancies
Secondary Objectives:
- To determine if the patient develops any evidence of anti-leukemic effect from the administration of CD34-TK75 transduced donor lymphocytes
- To determine if ganciclovir administration to patients who develop Graft versus Host Disease (GVHD)results in clinical improvement after infusions of CD34-TK75 transduced lymphocytes.
Sub-Study Objective
The primary purpose is to perform PET imaging of CD34-TK transduced allogeneic donor T cells in patients who have relapsed hematologic malignancies after allogeneic hematopoietic stem cell transplantation (SCT). At this time the limited amount of cGMP quality virus produced by the NGVL will likely permit the imaging of only 3 patients. Consequently our current objective will be to establish that the TK-expressing cells can be detected by 18FHBG-PET in patient organs relevant for performing additional studies that are currently in the planning stages and for which we are working to produce additional virus.
The ultimate objective will be to use the TK substrate 18FHBG to locate the donor T cells within the recipient as they exert anti-leukemic effects, and the T cells can then be eliminated in response to in vivo administration of ganciclovir, before morbidity and mortality from GvHD occurs. We will use the imaging strategy to define patterns of T cell trafficking in humans pre and post-DLI infusion, and to determine where the cells reside while they mediate GVL in contrast to GvHD. We expect to obtain in vivo PET imaging markers predictive of GvHD before clinical symptoms occur.
Detailed description
This is a phase I study of to determine the safety of the administration of lymphocytes, collected from the bone marrow donor. Donor lymphocytes are often administered in the case of a relapsed cancer after allogeneic bone marrow transplantation, in the hope to reduce the amount or size of the relapsed cancer. In this study, we will look for a decrease of the size of the relapsed cancer.
By inserting genetic material (DNA) into the cells (lymphocytes) collected from the donor, these cells will be genetically modified and made very sensitive to the killing effects of a drug called ganciclovir, routinely used in the clinic after bone marrow transplantation to treat virus infections in transplant patients.
This research study is to determine, if administration of the drug ganciclovir to the recipient, after intravenous infusion of the genetically modified cells (lymphocytes) into the recipient, will reduce or even eliminate a life threatening complication of allogeneic transplantation, called graft versus host disease (GvHD). The drug ganciclovir will kill the infused genetically modified donor cells (lymphocytes) so they cannot cause GvHD.
In summary, the overall purpose of this research study is to determine, if administration of a seven day course of the drug ganciclovir to the donor lymphocyte recipient will either decrease the severity of GvHD, or will decrease the number of cases with life-threatening GvHD after donor lymphocyte infusions.
This study will also determine if insertion of a small piece of DNA (a small piece of genetic material), makes these donor lymphocytes opened up and sensitive to the killing effects of the drug ganciclovir, but at the same time does not harm the lymphocytes' ability to reduce the amount or size of the cancer in the recipient. The DNA to be inserted into the donor lymphocytes is transported into these cells by a type of virus called "retrovirus vector". This retrovirus vector is made so the virus cannot divide (cannot make more of itself), and cannot make cells or the recipient sick. Retroviruses do, however, allow for the gene (DNA) they are carrying, to be permanently inserted into the genetic material of the donor lymphocytes. Therefore, this inserted DNA will persist in the donor lymphocytes for the life of the lymphocytes.
Finally, this study will also determine if the administration of genetically manipulated donor lymphocytes is well tolerated.
Sub Study
The goal of this subproject is to see if an imaging procedure called 18FHBG-PET/CT can help us see if the lymphocytes you received have gone to the sites in the body where the anti-cancer effects are taking place.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Donor lymphocyte infusion | Experimental | Genetic: CD34-TK75 transduced donor lymphocytes, Radiation: Sub Study - 18 FHBG PET/CT ScansCD34-TK75 transduced T lymphocytes from donors matched at a 5/6 or 6/6 antigen level at a dose of 1.0 x 105 cells/kg recipient weight. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Patients must be prior recipients of allogeneic BMT (matched 6/6 or 5/6 according to the National Marrow Donor Program) for any hematologic malignancy. Eligible patients would include those with leukemia, non Hodgkins Lymphoma, Hodgkins Disease, myelodysplastic syndrome and multiple myeloma.
- Patients must have laboratory, histologic, or cytogenetic evidence of disease relapse after allogeneic BMT.
- Patients may not have received prior therapy with transduced or non-transduced donor lymphocytes.
- Patients ≥ 18 years of age.
- The minimum number of transduced and purified lymphocytes from the same donor of donated cells for allogeneic transplant is is 1x105 per kg for all patients.
Key exclusion criteria (19 listed)
- Patients receiving immunosuppression (cyclosporin, FK506, prednisone, cellcept, methylprednisolone) for GvHD or other reasons at the time of lymphocyte infusion.
- Patients must not have evidence of active CMV or other active viral infection requiring antiviral therapy. A culture or PCR of blood for CMV must be negative for enrollment.
- Pregnant or lactating females.Note that a second and third high sensitivity pregnancy test (20mlU ß-HCG /ml urine as administered in the Center for Clinical Imaging Research, Mallinckrodt Institute of Radiology, Washington University) are required prior to each imaging session (i.e. at days 10-16 and days 27-33 for patients #3 to 8).
- Uncontrolled infection: Any uncontrolled viral, bacterial, or fungal infection.
- HIV infection.
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 |
|---|---|---|
| CD34-TK75 transduced donor lymphocytes | Genetic | Donor lymphocyte infusion |
| Sub Study - 18 FHBG PET/CT ScansThree 18 FHBG PET/CT Scans will be performed first one at pre-DLI infusion, second 14 days post-DLI infusion and third 30 days post-DLI infusion - patients #3 - #8 | Radiation | Donor lymphocyte infusion |
Primary outcome
To determine if there is significant toxicity associated with the administration of CD34-TK75 transduced donor lymphocytes after allogeneic BMT for relapsed hematologic malignancies
Time frame: Day 0 through Day 100
Occurrence of grade 3-5 toxicity 72 hour infusional toxicity Acute GVHD
Perform PET imaging to allow us to locate the donor T cells within the recipient as they exert anti-leukemic effects, and the T cells can then be eliminated in response to administration of ganciclovir, before morbidity and mortality from GvHD occurs
Time frame: Baseline, Day 14, and Day 30
To determine if there is significant toxicity associated with the administration of CD34-TK75 transduced donor lymphocytes after allogeneic BMT for relapsed hematologic malignancies
Time frame: Day 100 - Year 15
Occurrence of grade 3-5 toxicity
2 secondary outcomes
To determine if the patient develops any evidence of anti-leukemic effect from the administration of CD34-TK75 transduced donor lymphocytes
Time frame: 100 days
To determine if GCV administration to patients who develop GvHD results in clinical improvement after infusions of CD34-TK75 transduced lymphocytes.
Time frame: 100 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jul 2013.
- Background: PubMed 12842426Rettig MP, Ritchey JK, Meyerrose TE, Haug JS, DiPersio JF. Transduction and selection of human T cells with novel CD34/thymidine kinase chimeric suicide genes for the treatment of graft-versus-host disease. Mol Ther. 2003 Jul;8(1):29-41. doi: 10.1016/s1525-0016(03)00142-4.
- Background: PubMed 15356106Rettig MP, Ritchey JK, Prior JL, Haug JS, Piwnica-Worms D, DiPersio JF. Kinetics of in vivo elimination of suicide gene-expressing T cells affects engraftment, graft-versus-host disease, and graft-versus-leukemia after allogeneic bone marrow transplantation. J Immunol. 2004 Sep 15;173(6):3620-30. doi: 10.4049/jimmunol.173.6.3620.
- Background: PubMed 8400284Drobyski WR, Keever CA, Roth MS, Koethe S, Hanson G, McFadden P, Gottschall JL, Ash RC, van Tuinen P, Horowitz MM, et al. Salvage immunotherapy using donor leukocyte infusions as treatment for relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation: efficacy and toxicity of a defined T-cell dose. Blood. 1993 Oct 15;82(8):2310-8.
- Background: PubMed 3019523Moolten FL. Tumor chemosensitivity conferred by inserted herpes thymidine kinase genes: paradigm for a prospective cancer control strategy. Cancer Res. 1986 Oct;46(10):5276-81.
- Background: PubMed 2299679Moolten FL, Wells JM. Curability of tumors bearing herpes thymidine kinase genes transferred by retroviral vectors. J Natl Cancer Inst. 1990 Feb 21;82(4):297-300. doi: 10.1093/jnci/82.4.297.
- Background: PubMed 3785217Miller AD, Buttimore C. Redesign of retrovirus packaging cell lines to avoid recombination leading to helper virus production. Mol Cell Biol. 1986 Aug;6(8):2895-902. doi: 10.1128/mcb.6.8.2895-2902.1986.
- Background: PubMed 2404283Kasid A, Morecki S, Aebersold P, Cornetta K, Culver K, Freeman S, Director E, Lotze MT, Blaese RM, Anderson WF, et al. Human gene transfer: characterization of human tumor-infiltrating lymphocytes as vehicles for retroviral-mediated gene transfer in man. Proc Natl Acad Sci U S A. 1990 Jan;87(1):473-7. doi: 10.1073/pnas.87.1.473.
- Background: PubMed 8049449Tiberghien P, Reynolds CW, Keller J, Spence S, Deschaseaux M, Certoux JM, Contassot E, Murphy WJ, Lyons R, Chiang Y, et al. Ganciclovir treatment of herpes simplex thymidine kinase-transduced primary T lymphocytes: an approach for specific in vivo donor T-cell depletion after bone marrow transplantation? Blood. 1994 Aug 15;84(4):1333-41.
- Background: PubMed 7548281Bordignon C, Bonini C, Verzeletti S, Nobili N, Maggioni D, Traversari C, Giavazzi R, Servida P, Zappone E, Benazzi E, et al. Transfer of the HSV-tk gene into donor peripheral blood lymphocytes for in vivo modulation of donor anti-tumor immunity after allogeneic bone marrow transplantation. Hum Gene Ther. 1995 Jun;6(6):813-9. doi: 10.1089/hum.1995.6.6-813.
- Background: PubMed 11133743Tiberghien P, Ferrand C, Lioure B, Milpied N, Angonin R, Deconinck E, Certoux JM, Robinet E, Saas P, Petracca B, Juttner C, Reynolds CW, Longo DL, Herve P, Cahn JY. Administration of herpes simplex-thymidine kinase-expressing donor T cells with a T-cell-depleted allogeneic marrow graft. Blood. 2001 Jan 1;97(1):63-72. doi: 10.1182/blood.v97.1.63.
- Background: PubMed 8622970Black ME, Newcomb TG, Wilson HM, Loeb LA. Creation of drug-specific herpes simplex virus type 1 thymidine kinase mutants for gene therapy. Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3525-9. doi: 10.1073/pnas.93.8.3525.
- Background: PubMed 8435660Szer J, Grigg AP, Phillips GL, Sheridan WP. Donor leucocyte infusions after chemotherapy for patients relapsing with acute leukaemia following allogeneic BMT. Bone Marrow Transplant. 1993 Feb;11(2):109-11.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
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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.
John F. DiPersio, M.D., Ph.D. principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CD34-TK75 transduced donor lymphocytes and Sub Study - 18 FHBG PET/CT Scans in people with Leukemia and Lymphoma, Non-Hodgkin, run by Washington University School of Medicine 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 25 inclusion and 19 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 11 Jul 2013. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To determine if there is significant toxicity associated with the administration of CD34-TK75 transduced donor lymphocytes after allogeneic BMT for relapsed hematologic malignancies (time frame: Day 0 through Day 100). 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 NCT00871702, which also lists 17 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 11 Jul 2013.