A Phase 1/2 interventional study of donor-derived CIK cells in Relapsed Hematologic Malignancy, 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 1/2, Interventional, and Treatment
The haematological neoplasia relapse is the cause of higher mortality after allogeneic stem cell transplantation (HSCT). When transplantation fails the most common therapeutic strategy is to increase the antitumor activity of the donor's immune system through the infusion of donor Lymphocytes (DLI). The use of DLI may limit the relapse, but may induce transplantation disease against the host (GvHD), in 40-60% of patients. With advances in transplantation procedures, the use of non-compatible (HLA-mismatched) haploidentical (aplo) donor cells has become feasible and is increasing. However, strategies for immune control of relapse after HSCT from haploidentical donor are hampered by the absence of prospective data that can guide treatment and limit the induction of GvHD in the setting of the HLA difference between the donor and the recipient. Cytokine-induced Killer Cells (CIK) are T lymphocytes from haploidentical donor expressing CD56 (e.g., double positive cells at CD3 / CD56). CIK are a product of advanced cell therapy (Advanced Therapeutic Medicinal Product, ATMP) for somatic cell therapy and have a reduced histocompatibility (MHC) complex: are cytotoxic, anti-tumor cells, possess the characteristics of both T cells and Natural Killer (NK) and show in vivo a very strong cytolytic activity against leukemia, but a low reactivity against the host. Therefore, this study has as its primary objective to investigate the safety of CIK cells deriving from the donor, especially in terms of the onset of GvHD, used as a treatment for relapse after transplantation with haploidentical stem cells. The study will allow to evaluate the possibility of using CIK cells, at the indicated dose combination (5x10 * 6 cells / kg, 5x10 * 6 and 10x10 * 6 cells / kg) as an effective and safe therapy in the context of haploidentical transplantation.
Disease relapse is a major cause of mortality following allogeneic hematopoietic stem cell transplantation (HSCT) for hematologic malignancies. When allogeneic transplant fails the most common therapeutic strategy is to increase the anti-tumor activity of donor immune system through infusion of donor lymphocytes (DLI). Use of DLI can effectively treat limited relapses, but can induce graft-versus-host disease (GvHD) in the range of 40-60% of the patients. With the advances in HSCT procedure, the use of HLA-mismatched (haplo) family donors became feasible and extended the opportunity for HSCT to almost all patients lacking an HLA-matched donor. Due to the promising results of the procedure and the easier access to the donor, the number of haplo-HSCT transplant is steeply increasing. However, strategies aiming at eliciting the immune control of the relapse after haplo-HSCT are hampered by absence of prospective data that guide treatment and the fear of inducing GvHD in this setting of profound HLA disparity between donor and recipient.
1,444 studies on the registry are indexed under Hematologic Neoplasms; 420 are open to participants now.
This study's planned enrollment of 20 is below the median of 46 across 1,044 interventional studies indexed under Hematologic Neoplasms.
Browse Hematologic Neoplasms studies →A.O. Ospedale Papa Giovanni XXIII is the lead sponsor of 32 studies on the registry; 2 are open to participants now.
Counted across the registry records on this site, refreshed daily.
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.
To be enrolled to the safety run-in cohort, patients must have:
To be enrolled to the phase II cohort, patients must have:
For female patients:
Exclusion Criteria:
The presence of any of the following will exclude a subject from study enrolment 1. Donors positive for , ( virus) HBV, ( virus) HCV, Treponema or unfit to donate peripheral blood mononuclear cells 2. Patients with active grade 2 or more acute or moderate chronic at study entry or before CIK infusion 3. Patients with rapidly progressive disease or not controlled by palliative supportive treatments, including chemotherapy, and with less than 8 weeks 4. Any serious medical or psychiatric illness, including drug or alcohol abuse, that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol
-
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.
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
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.
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.
After a transplant from a donor, the donor’s immune cells attack the recipient’s body, often the skin, gut or liver.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Allogeneic and autologous transplant
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
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.
GVHD (graft-versus-host disease)
After a transplant from a donor, the donor’s immune cells attack the recipient’s body, often the skin, gut or liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biological: donor-derived CIK cells
Treatment plan will be based on three infusions of donor derived CIK cells given by 3 weeks intervals at increasing dose levels. No dose changes are allowed and the following planned dose levels will be administered to each patient enrolled: 5x106, 5x106 and 10x106 cells/Kg according to the dose escalating program
Number of deaths related to study treatment death
Death, with related attributed cause of the event (e.g. treatment, toxicities, disease, other) will be assessed
Time frame: Within 3 weeks after the last CIK cells infusion.
Incidence of grade >=III acute GvHD
Will be collected: date of onset, organ involvement and maximum grade of acute GVHD Staging and Grading of Acute GvHD will be evaluated according to Glucksberg.
Time frame: Within 3 weeks after the last CIK cells infusion.
Incidence of grade >= III acute GvHD
Will be collected: date of onset, organ involvement and maximum grade of acute GVHD. Staging and Grading of Acute GvHD will be evaluated according to Glucksberg.
Time frame: at +100 days after the last infusion of CIK cells
Incidence of any grade acute GvHD
Will be collected: date of onset, organ involvement and maximum grade of acute GVHD. Staging and Grading of Acute GvHD will be evaluated according to Glucksberg criteria.
Time frame: at day +100 after last CIK infusion
Incidence of any grade chronic GvHD
Chronic GVHD will be evaluated according to the National Institutes of Health Consensus Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: Diagnosis and Staging Working Group Report. The following data will be collected: date of onset, organ involvement, maximum organ score and maximum global scoring of chronic GVHD.
Time frame: at days +100, +365 after last CIK infusion
Incidence of Adverse events (AEs) and laboratory abnormalities.
Number, causality and intensity of all adverse events occurring during the study 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: Up to 365 days from last CIK infusion
Evaluation of Response of Disease
Response of Disease will be assessed based on detection of any evidence of molecular, cytogenetic, chimerism or hematologic disease progression, including loss of complete donor chimerism.
Time frame: at day +21, +100 and +365 after the last CIK cell infusion, or before if clinically indicated according to Investigator's judgment. For patients with acute leukemia disease response will be evaluated also after 60 days from the last CIK infusion.
Progression Free Survival
Progression free survival will be estimated as the probability of patients of being alive free of progression (stable disease) or free of disease since enrollment up to 1 year after last cells infusion (day +365). Thus, death for disease, disease relapse and disease progression are treated as events. (Death for other cause than disease will treated as competing events). Patients alive, patients in stable disease and those free of disease at their last follow-up will be censored.
Time frame: Since enrollment up to 1 year after last cells infusion (day +365).
Overall Survival
Overall survival will be estimated as the probability of survival irrespective of disease state since enrollment up to 1 year after last cells infusion (day +365). Patients alive at their last follow-up are censored.
Time frame: Since enrollment up to 365 days after last CIK infusion
This study is status unknown, as verified in Dec 2021. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
A.O. Ospedale Papa Giovanni XXIII