Relapsed Hematologic Malignancy Clinical Trial
— Haplo-CIKOfficial title:
Phase I/II Trial of Donor Derived Cytokine Induced Killer (CIK) Cells Infusion for Relapsed Hematologic Malignancy After Haploidentical Stem Cell Transplantation
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.
Status | Recruiting |
Enrollment | 20 |
Est. completion date | May 2023 |
Est. primary completion date | May 2022 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: 1. Male or female patients 18 years or older 2. Patients treated with haploidentical allogeneic transplantation for hematologic malignancies, excluding Chronic Myeloid Leukemia (CML), such as acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), multiple myeloma (MM), myelofibrosis (MF) and myelodysplastic syndrome (MDS) 3. To be enrolled to the safety run-in cohort, patients must have: - Evidence of relapsed disease after allogeneic transplantation, including molecular, cytogenetic or overt hematologic relapse To be enrolled to the phase II cohort, patients must have: - Evidence of relapsed disease after allogeneic transplantation, including, molecular, cytogenetic or overt hematologic relapse, or - Mixed chimerism after the day +90, defined as <75% donor in unfractionated bone marrow and/or <75% donor in unfractionated Peripheral blood (PB) and/or <75% donor in fractionated CD3+ peripheral blood. 4. Availability of a donor willing to donate peripheral blood mononuclear cells 5. Withdrawn of immune suppression at least 3 weeks before the beginning of the cell therapy program 6. Written informed consent prior to any study procedures being performed 7. For female patients: 1. being postmenopausal for at least 1 year before the screening visit,OR 2. being surgically sterile, OR 3. if they are of childbearing potential, must agree to practice highly effective method of contraception and one additional effective (barrier) method from the time of signing the informed consent until the end of study. Highly effective method of contraception includes: (i) combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, transdermal; (ii) progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, implantable (intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner, sexual abstinence) OR 4. must agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject from the time of signing the informed consent until the end of study. [Periodic abstinence (eg, calendar, ovulation, symptothermal, postovulation methods), withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.] 8. For male patients, even if surgically sterilized (i.e., status postvasectomy): a) with female partners of childbearing potential: must agree to practice barrier contraception (condom with or without spermicide) from the time of signing the informed consent until the end of study and his female partner must agree to practice method of contraception including one of the following: estrogen and progestogen containing hormonal contraception; inhibition of ovulation: oral, intravaginal, transdermal; progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, implantable (intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion) from the time of signing the informed consent until the end of study.b) must agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject from the time of signing the informed consent until the end of study. [Periodic abstinence (eg, calendar, ovulation, symptothermal, postovulation methods), withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.] c) must agree to refrain from donating sperm Exclusion Criteria: The presence of any of the following will exclude a subject from study enrolment 1. Donors positive for HIV, (Hepatitis B virus) HBV, (Hepatitis C virus) HCV, Treponema or unfit to donate peripheral blood mononuclear cells 2. Patients with active grade 2 or more acute or moderate chronic GVHD at study entry or before CIK infusion 3. Patients with rapidly progressive disease or not controlled by palliative supportive treatments, including chemotherapy, and with life expectancy 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 - |
Country | Name | City | State |
---|---|---|---|
Italy | A O Papa Giovanni XXIII | Bergamo |
Lead Sponsor | Collaborator |
---|---|
A.O. Ospedale Papa Giovanni XXIII |
Italy,
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* Note: There are 25 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | Within 3 weeks after the last CIK cells infusion. | |
Primary | 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. | Within 3 weeks after the last CIK cells infusion. | |
Primary | 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. | at +100 days after the last infusion of CIK cells | |
Secondary | 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. | at day +100 after last CIK infusion | |
Secondary | 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. |
at days +100, +365 after last CIK infusion | |
Secondary | 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). | Up to 365 days from last CIK infusion | |
Secondary | 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. | 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. | |
Secondary | 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. |
Since enrollment up to 1 year after last cells infusion (day +365). | |
Secondary | 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. |
Since enrollment up to 365 days after last CIK infusion |
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