Please select the eligibility criteria that correspond to the clinical trial below.
Title: Phase I/II Dose-escalation Study of the Investigational Trifunctional Bispecific Anti-CD20 x Anti-CD3 Antibody FBTA05 in Combination With Donor Lymphocyte Infusion (DLI) in Patients With CD20 Positive Chronic Lymphocytic Leukemia (CLL), Low and High Grade Non-Hodgkin´s Lymphoma (NHL) After Allogeneic Stem Cell Transplantation
Brief Summary: This study is an investigator driven, open-label, non-randomized, uncontrolled, dose escalating Phase I/II study evaluating the safety and preliminary efficacy of the trifunctional bispecific antibody FBTA05 in combination with donor lymphocyte infusions (DLI) for treatment of relapsed or refractory disease in CD20 positive either low- or high-grade non-Hodgkin´s lymphoma after allogeneic transplantation


Options:
A: Inclusion Criteria:

1. Male and female subjects with CD19 expressing B-cell acute lymphoblastic leukemia (ALL) or Non-Hodgkin Lymphoma (NHL) with BM involvement and one of the following:

   i. Patients in 2nd or subsequent relapse, after at least one standard frontline chemotherapy and one salvage regimen, with BM involvement ii. Relapse after allogeneic HSCT, if at least 100 days post-transplant, if there is no evidence of active GVHD and if the patient is no longer taking immunosuppressive agents for at least 30 days prior to enrollment iii. MRD \> 0.1% after either reinduction therapy or any course of consolidation for relapsed ALL
2. Measurable or evaluable disease at the time of enrollment, which may include any evidence of disease, including MRD detected by flow cytometry, cytogenetics, or polymerase chain reaction (PCR) analysis.
3. Age: 6 months - 25 years.
4. Voluntary informed consent is given. For subjects \< 18 year-old their legal guardian must give informed consent. Pediatric subjects will be included in age-appropriate discussion and verbal assent will be obtained for those greater than or equal to 12 years of age, when appropriate.
5. Clinical performance status: Patients \> 16 years of age: Karnofsky greater than or equal to 60%; Patients \< 16 years of age: Lansky scale greater than or equal to 60%.
6. Patients of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study and for four months after receiving the preparative regimen.
7. Females of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects on the fetus.

Exclusion Criteria:

1. Pregnant or lactating women
2. Severe, uncontrolled active intercurrent infections
3. HIV, or active HCV and/or HBV infection
4. Life-expectancy \< 6 weeks
5. Hepatic function: Inadequate liver function defined as total bilirubin \> 4x upper limit of normal (ULN) or transaminase (ALT and AST) \> 6 x ULN
6. Renal function: serum creatinine \> 3x ULN for age.
7. Blood oxygen saturation \< 90%.
8. Cardiac function: Left ventricular ejection fraction lower than 45% by ECHO.
9. Congestive heart failure, cardiac arrhythmia, psychiatric illness, or social situations that would limit compliance with study requirements or in the opinion of the PI would pose an unacceptable risk to the subject.
10. BM blasts \> 50% pre-infusion.
11. Hyperleukocytosis (greater than or equal to 20,000 blasts/microliter) or rapidly progressive disease that in the evaluation of the investigator would compromise ability to complete study therapy
12. Active CNS disease as documented by the presence of blasts in the CSF or by MRI. This criterion could be revised once that, after the phase I portion of the study, absence of life-threatening (i.e. grade IV) neurological toxicity will be documented.
13. Presence of active, grade 2-4 acute or extensive chronic GvHD
14. Recurrent or refractory ALL with testicular involvement
15. Concurrent or recent prior therapies, before infusion:

    i. Systemic steroids (at a dose \> 2 mg/kg prednisone) in the 2 weeks before infusion. Recent or current use of inhaled/topical/non-absorbable steroids is not exclusionary.

    ii. Systemic chemotherapy in the 2 weeks preceding infusion. iii. Anti-thymocyte globulin (ATG) or Alemtuzumab (Campath®) in the 4 weeks preceding infusion.

    iv. Immunosuppressive agents in the 2 weeks preceding infusion. v. Radiation therapy must have been completed at least 3 weeks prior to enrollment.

    vi. Other anti-neoplastic investigational agents currently administered or within 30 days prior to infusion (i.e. start of protocol therapy);

    vii. Exceptions:
    1. There is no time restriction with respect to prior intrathecal chemotherapy, provided that there is complete recovery from any acute toxic effects of such;
    2. Patients who relapse while receiving standard ALL maintenance chemotherapy will not be required to have a waiting period before entry onto this study provided that they meet all other eligibility criteria;
    3. Subjects receiving steroid therapy at physiologic replacement doses only are allowed provided that there has been no increase in dose for at least 2 weeks prior to starting apheresis;
16. Patient-derived CD19-CART01 production failure
B: Inclusion Criteria:

Eligibility is determined priori to leukapheresis. Patients must satisfy the following criteria to be enrolled in this study:

1. Signed Informed Consent Form
2. Male or female patients who are 18-75 years of age
3. Histologically confirmed ALCL, PTCL- NOS, ENKTCL nasal type, DLBCL-NOS and PMBCL
4. Relapsed or refractory CD30-positive NHL who have failed all available standards of therapy. Patients may or may not have received an autologous or allogeneic HSCT CD30-positive tumor
5. At least 1 measurable lesion according to the Lugano Classification
6. ECOG PS of 0 to 1 or equivalent Karnofsky PS Anticipated life expectancy \>12 weeks

Exclusion Criteria:

1. CNS involvement by malignancy
2. Inadequate laboratory abnormalities at screening:

   Hgb ≤ 8.0 g/dL Total bilirubin \> 1.5 x ULN (\>2 x ULN for patients with Gilbert's syndrome) AST and ALT ≥ 5 x ULN CrCL ≤ 45 mL/min (as measured by Cockcroft-Gault equation) ANC ≤ 1000/uL Platelets ≤75,000/uL PR or INR \>1.5 x ULN aPTT\> 1.5 x ULN
3. Active uncontrolled bleeding or a known bleeding diathesis
4. Inadequate pulmonary function defined as pulse oximetry \< 90% on room air
5. Ongoing treatment with immunosuppressive drugs including calcineurin inhibitions, TNFalpha, mTOR, etc or chronic systemic corticosteroids (\>10 mg/day prednisone or equivalent for \>48 hours)
6. Received prior therapy of:

   Anti-CD30 Ab based therapy within the previous 8 weeks Previous CD30.CAR-T investigational product Bi-specific CD30 Ab within the previous 8 weeks Allogenic HSCT in the last 180 days Autologous HSCT within 90 days
7. Active GVHD requiring immune suppression regardless of grade
8. HIV positive
9. Active HBV and/or HCV
C: Inclusion Criteria:

* Patient´s written informed consent
* ≥ 18 years of age; male and female
* Confirmed CLL, low grade NHL or high grade NHL on standard histological or immunophenotypical criteria described in the WHO classification of lymphoid malignancies
* CD20 positivity (if not already confirmed)
* Adequate haematological, liver and kidney functions
* Platelet count ≥25,000mm³ (=25 x 10\^9/l)
* Patients with active disease (relapsed/refractory) that survived at least 60 days after allogeneic transplantation
* Eastern Cooperative Oncology Group (ECOG) performance status \<=2 (Appendix IV)
* Negative pregnancy test (no more than 2 days before enrolment) and adequate contraception during the study in women of child bearing potential (pre- menopausal, \<2 years post-menopausal or not surgically sterile)

Exclusion Criteria:

* Any anti-CD20 and / or any other anti-T cell directed antibody treatments \< 3 months before application of FBTA05
* Positivity for human anti-mouse antibodies (HAMAs)
* History of GvHD ° III or IV, or GvHD requiring steroid therapy with more than 10 mg/day
* Known or suspected hypersensitivity to recombinant, murine or rat proteins
* AST/SGOT greater than 10 x ULN (grade 3, CTCAE)
* Bilirubin greater than 5 x ULN (grade 3, CTCAE)
* Creatinine greater than 3.5 mg/dl (grade 3, CTCAE)
* Acute or uncontrolled chronic infections, viral infections at risk of reactivation (e.g.HCV, HBV, HIV)
* Unable or unwilling to comply fully with the protocol
* Any condition which in the judgement of the Investigator would place the subject at undue risk or interfere with the results of the study
D: Inclusion Criteria:

* Metastatic Melanoma patients failing to prior chemo and immunotherapy with good performance status.

Exclusion Criteria:

* Brain mets

Answer: C