HA-1H TCR T Cell for Relapsed/Persistent Hematologic Malignancies After Allogeneic Stem Cell Transplantation

Korábbi kezelés

• Participation in any clinical study < 60 days prior to first IMP administration in case of antibodies and < 14 days for all other IMPs
• If not enough starting material is collected during leukapheresis, the patient will be excluded from study participation and receive best available standard therapy.

Más betegség

• Evidence of acute or chronic graft versus host disease (GVHD) ≥ grade II
• Serologic evidence of acute or chronic hepatitis B virus infection (i.e. positive for HBsAg or IgM anti-HBc). Positive HIV and HCV serology or active bacterial infection
• Clinically significant and ongoing immune suppression including, but not limited to immunosuppressive agents (e.g. cyclosporine or corticosteroids (at an equivalent dose of ≥ 10 mg prednisone per day)). Inhaled steroid and physiological replacement for adrenal insufficiency is allowed
• Patients with a history of primary immunodeficiency
• Patients with a currently active second malignancy other than nonmelanoma skin cancers or subjects with history of prior malignancy and previously treated with a curative intent therapy less than 1 year ago
• Known or suspected hypersensitivity or intolerance to IMP, cyclophosphamide, fludarabine and/or tocilizumab or to any of the excipients
• Uncontrolled central nervous system (CNS) disease
• Uncontrolled, life threatening infections or uncontrolled disseminated intravascular coagulation; however, if these problems resolve, the start of treatment can be initiated on a delayed schedule
• Evidence of acute or chronic graft versus host disease (GVHD) ≥ grade II

Laborértékek

• Medical or psychological conditions that would make the patient unsuitable candidate for cell therapy at the discretion of the investigator. Special risks to be considered:
  • Creatinine > 2.5 times the upper limit of normal (ULN) serum level
  • Total bilirubin, ALAT, ASAT > 3.0 x ULN serum level
  • Cardiac left ventricular ejection fraction < 35% at rest
  • Severe restrictive or obstructive lung disease
• Women of child-bearing potential not using highly effective method(s) of birth control (i.e., with low failure rate < 1% per year) throughout the study and/or unwilling to be tested for pregnancy. A negative serum β-hCG test is required at baseline

Egyéb

• Patients both with urinary outflow obstructions and on dialysis or patients for whom cyclophosphamide is contraindicated for other reasons
• Vulnerable patients and/or patients unwilling or unable to comply with procedures required in this clinical study protocol
• Pregnant or lactating women
• Fertile men not agreeing to use effective contraceptive methods during the clinical study
• Unable to generate HA-1H TCR transduced T cells for transfusion (out of specification). However, if a lower than planned number of cells is available, the patient will have the option to receive the OOS HA-1H TCR transduced T cells product (cell dose must be at least the lowest dose level of D1 and will be analyzed in the safety and full analysis set populations.

• Relapsed or persistent disease is defined according to disease specific guidelines (AML, CML, MM, ALL, MDS, MPN, MF and malignant B- or T-cell lymphoma) and includes MRD positivity.
• Patients positive for HLA-A*02:01 according to genotyping results
• Patients positive for HA-1H
• Patients who received the allo-HSCT at least 100 days preceding the leukapheresis
• Patients (i.e. recipient) transplanted with a sibling or unrelated HSCT donor
  • donor being HLA-A*02:01 positive and HA-1H negative, or
  • a donor with a single mismatch at HLA-A*02:01, being HA-1H positive or negative
• Patients from whom at least 10x10\^6 donor CD8+ T cells can be harvested by leukapheresis
• Age ≥ 18 years, of either sex
• ECOG performance status 0-2.
• Life expectancy of at least 3 months
• Patients must be able to understand and be willing to give signed informed consent