A Phase 1 interventional study of Blinatumomab Expanded T-cells (BET) in Indolent Non-Hodgkin Lymphomas/Chronic Lymphocytic Leukemia, sponsored by A.O. Ospedale Papa Giovanni XXIII. Status unknown at 1 site in Italy. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-12-23.
Sponsored by A.O. Ospedale Papa Giovanni XXIII · Phase 1, Interventional, and Treatment
Non-Hodgkin CD20 + Indolent Lymphoma (iNHL) and Chronic Lymphatic Leukemia (CLL) are the most frequent neoplasms of B lymphocytes. They include various histologies (follicular NHL, marginal zone NHL and Lymphocytic NHL/ CLL) characterized by a chronic course and prolonged survival, but while patients with a limited disease could be cured, those with advanced disease or relapsed after localized radiation therapy are generally considered untreatable through standard treatments. The options for first-line therapy include the use of the FCR scheme, based on Fludarabine, Cyclophosphamide and Rituximab or the BR, with Bendamustine and Rituximab. Despite good results, treatment with these two regimens (FCR or BR) is associated with severe immunosuppression which worsens the immunological dysfunction already present at diagnosis in several patients. It has been shown previously that the adoptive transfer of ex vivo anti-CD3/CD28 co-stimulated autologous T cells can successfully accelerate a robust early recovery of T cells after autologous transplantation in multiple myeloma. These CD3/CD28 expanded T cells cannot however be used in NHLi and CLL due to the presence of contaminating tumor cells in the preparation. Polyclonal T cells can also be expanded in vitro in presence of Blinatumomab and recombinant human IL2 (rhIL2) and have been called BET (Blinatumomab-expanded T cells). They are a product of Advanced Therapeutic Medicinal Product (ATMP) composed of polyclonal CD8 and CD4 T cells that are still functional and devoid of contaminating CD19+ neoplastic cells. Based on these data, it was hypothesized that infusion of BET in patients with iNHL/CLL, after the first treatment line (with FCR or BR), could induce adequate immunological recovery.
2,036 studies on the registry are indexed under Leukemia, Lymphocytic, Chronic, B-Cell; 237 are open to participants now.
This study's enrollment of 19 is below the median of 39 across 1,603 interventional studies indexed under Leukemia, Lymphocytic, Chronic, B-Cell.
Browse Leukemia, Lymphocytic, Chronic, B-Cell studies →A.O. Ospedale Papa Giovanni XXIII is the lead sponsor of 32 studies on the registry; 2 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Male or female patients 18 years or older 2. Confirmed diagnosis of the following CD20+ iNHL or CLL according to (World Health Organization ) WHO criteria:
Additional inclusion criteria to be met at study entry (i.e. before BET infusion):
For male patients, even if surgically sterilized (i.e., status postvasectomy):
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Adults diagnosed with indolent non-Hodgkin lymphomas (iNHL) or chronic lymphocytic leukemia (CLL) in need of first line treatment consisting of either FCR or BR as per investigator assessment
Biological: Blinatumomab Expanded T-cells (BET)
Two to five days after the last chemotherapy infusion, BET will be administered. An accelerated titration dose escalation design will be used. During dose escalation, up to four dose levels (see table) will be evaluated or until (Maximum Tolerated Dose) MTD is reached. Dose level BET dose(Counted on CD3+ cells) 1. (starting dose) 3.0 x 109 2. 6.0 x 109 3. 9.0 x 109 4. 12.0 x 109
Number of grade 3 or 4 adverse events (AE) possibly related to therapy
Description and grading of all adverse events will be based on the NCI -CTCAE v4.03 and MedDra code (current version).
Time frame: The period of observation is during 14 days after BET infusion
Number of Adverse event (AE) and laboratory abnormalities.
Number, causality and intensity of all adverse events will be evaluated according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) V4.03 and MedDRA code (current version).
Time frame: From date of study start up to 180 days after BET infusion
Evaluation of Optimal Biological Dose (ODB) of BET cells
OBD of BET will be defined as the absolute number of BET cell that will allow a CD3+ count of \> 600 x106/L at +90 days after infusion in at least 70% of the patients.
Time frame: +90 days after infusion
Evaluation of general Immune Reconstitution after BET infusion
Absolute numbers of B, T, and NK cells reconstitution and its correlation with BET cell infused and its composition (in terms of T-cell subsets and NK cells)
Time frame: at +0 (4 hours), +30, +90 and +180 days after infusion
Evaluation of ex vivo transfer of anti-viral immunity
Ex vivo transfer of anti-viral immunity in terms of tetramer-based quantification of CMV-specific CD8+ T lymphocytes (this will be done only for CMV positive patients for whom CMV specific tetramers stain positive in starting peripheral blood or BET).
Time frame: at +0 (4 hours), +30, +90 and +180 days after infusion
Ran from Dec 2018 to primary completion in Nov 2021, 34 months.
Of 96 non-industry phase 1 interventional studies under Leukemia, Lymphocytic, Chronic, B-Cell, half reached primary completion within 56 months of starting (the median), counting those still running; a quarter within 39 and three quarters within 91. This study's 34 months is below that.
Counting every sponsor, half of 180 studies reached it within 56 months; a quarter within 39 and three quarters within 82.
How these figures are worked out, and which studies are left out of them.
This study is status unknown, as verified in Dec 2021. You cannot join it, but the record below documents what was studied.
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Leukemia, Lymphocytic, Chronic, B-Cell →
A.O. Ospedale Papa Giovanni XXIII