Multicenter, open-label, adaptive design phase I trial with genetically modified T-cells carrying Universal Chimeric Antigen Receptors (UniCAR02-T) in combination with CD123 target module (TM123) for the treatment of patients with hematologic and lymphatic malignancies positive for CD123

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 10

Inclusion Criteria

Inclusion criteria for phase 1a dose escalation:
1. Male or female patients, age >= 18 years
2. Documented definitive diagnosis of AML or BPDCN (according to standard of
care testing) and CD123 positivity of >=20 % of blasts. In the case of MRD+ AML,
if there are insufficient blasts at screening for CD123 testing, the most
recent available sample with sufficient blasts should be used.
- Relapsed or refractory AML, defined as:
a. patients having received standard induction chemotherapy: either refractory
to standard induction treatment,
b. or relapse, up to 3rd relapse, including conversion to MRD positivity within
6 months after achieving 1st CR, or relapse (not including conversion to MRD
positivity only) later than 6 months after 1st CR and refractory to standard
salvage regimen,*
c. or relapse after >= 2nd CR and not eligible for curative treatment (i.e.,
allogeneic blood stem cell transplantation).
d. First relapse after allogeneic HSCT including conversion to MRD positivity;
subjects must be at least 2 months from HSCT at the time of screening and off
immunosuppressant medication for at least 1 month at the time of screening
(with the exception of low-dose steroids (<= 20 mg prednisone or equivalent) and
have no active graft versus host disease (GvHD).*
e. MRD positive CR measured after having received two standard induction
chemotherapy cycles and one line of FLT3 inhibiting compound in eligible
patients*
f. Patients not eligible for standard induction chemotherapy: either refractory
or progressive after at least 1 cycle of demethylating agents in AML patients
not qualifying for intensive induction chemotherapy.
g. Patients with rrAML having up to 30% blasts in a bone marrow
assessment at either screening or prescreening, or patients having between 30%
and 40% blasts for 2 consecutive bone marrow assessments with a minimum of 1
months and no more than 2 months apart and without hyperproliferative disease
requiring cytoreductive treatment. Exceptions to BM blast criterion are only
possible in minor deviations in timing and/or blast count in clinically stable
patients, and only with sponsor*s approval.

- Relapsed or Refractory BPDCN:
a. Patients with histological and/or cytological evidence of BPDCN in the
peripheral blood, bone marrow (BM), spleen, lymph nodes, skin, and/or other
sites that is persistent/recurrent following prior standard of care treatment
for BPDCN. Inclusion of BPDCN requires documented approval by the sponsor
before entering into (pre)screening.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

Inclusion criteria for phase 1b dose expansion
1. Male or female patients, age >= 18 years.
2. Relapsed or refractory AML (according to standard of care testing), having
up to 30% blasts in a Bone Marrow assessment at either screening or
prescreening, or patients having between 30 and 40% blasts for 2 consecutive
bone marrow assessments with a minimum of 1 months and no more than 2 months
apart, and without hyperproliferative disease requiring cytoreductive
treatment, up to 3rd relapse, without further approved curative or
life-extending treatment options, and documented CD123 positivity of >= 20 % of
blasts. Exceptions to BM blast criterion are only possible in minor deviations
in timing and/o

Exclusion Criteria

Exclusion criteria for phase 1a dose escalation:
1. Acute promyelocytic leukemia (t15;17)
2. Refractory disease under anti-leukemic treatment lasting longer than 6 months
3. Manifestation of AML or BPDCN in central nervous system
4. Bone marrow failure syndromes (e.g., Fanconi anemia, Kostman syndrome,
Shwachman syndrome)

Exclusion criteria for phase 1b dose expansion
1. Acute promyelocytic leukemia (t15;17)
2. AML with only extramedullary manifestations (e.g., chloroma, primary myeloid
sarcoma).
3. Refractory disease under anti-leukemic treatment lasting longer than 6
months
4. Current manifestation of AML in central nervous system

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary Endpoints - Phase 1a Dose Escalation and Re-initiated Dose Escalation<br /><br>in 3+3 design:<br /><br>• Safety and tolerability<br /><br>• Incidence of dose limiting toxicity (DLT)<br /><br>• Maximum tolerated dose (MTD)<br /><br><br /><br>Primary Endpoints - Phase 1b Expansion:<br /><br>• Safety and tolerability<br /><br>• Establishing recommended phase 2 dose (RP2D) and schedule<br /><br>• Complete (CR, CRh, CRi, CR MRD neg, CR MRD pos) and partial remission (PR) at<br /><br>any time point and duration of responses</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary endpoints - Phase 1a Dose Escalation, Re-initiated Dose Escalation in<br /><br>3+3 design and Ph1b Expansion<br /><br>• Establishing recommended phase 2 dose (RP2D)<br /><br>• Complete (CR, CRh, CRi, CRMRDneg, CRMRDpos) and partial remission (PR) at any<br /><br>time point and durations<br /><br>• Disease stabilization (DS, i.e., no progressive disease or remission,<br /><br>including partial remission)<br /><br>• Best response rate<br /><br>• Progression free survival (PFS)<br /><br>• Overall survival (OS)<br /><br>• Toxicity and efficacy in repeated cycles of TM123 administration</p><br>