Dose-Escalation and Dose-Expansion Study to Evaluate the Safety and Tolerability of Anti-CD7 Allogeneic CAR T-Cells (WU-CART-007) in Patients With CD7+ Hematologic Malignancies

Inclusion Criteria:

Specific criteria apply to each disease subtype with T-NHL and AML cohorts.

In general, all patients must have CD7 expression and confirmed diagnoses of T-cell non Hodgkin lymphoma or acute myeloid leukemia (any subtype except acute promyelocytic leukemia) according to World Health Organization (WHO) classification29, and have relapsed or refractory disease.

For the T-NHL cohort, patients will have T-cell non-Hodgkin lymphoma with relapsed or refractory disease defined as one of the following:

-Relapsed or refractory after at least 2 or more prior lines of therapy (for patients with anaplastic large cell lymphoma, they must have prior therapy brentuximab vedotin). For patients with T-PLL, only 1 or more prior line of therapy is required.

OR

Relapsed after autologous or allogeneic hematopoietic cell transplant.

Permissible T-cell NHL subtypes will include:

angioimmunoblastic T-cell lymphoma (AITL)
enteropathy-associated T-cell lymphoma (EATL)
monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL)
peripheral T-cell lymphoma (PTCL) NOS
anaplastic large cell lymphoma (ALCL)
adult T-cell leukemia/lymphoma
T-cell prolymphocytic leukemia (T-PLL)
extranodal NK/T cell lymphoma
transformed mycosis fungoides/Sezary Syndrome
primary cutaneous gamma/delta T-cell lymphoma
hepatosplenic T cell lymphoma

For the AML cohort, patients will have Acute Myeloid Leukemia with relapsed or refractory disease unlikely to benefit from standard therapy defined as one of the following:

-Primary refractory AML defined as:

Minor or no response to intensive induction chemotherapy with more than 15% blasts and less than 50% proportional reduction in blast percentage after C130

Absence of morphological CR/CRi following either:

2 cycles of intensive induction chemotherapy
2 cycles of HMA plus venetoclax, or
4 total cycles of an HMA

OR

-Morphologic relapse (≥ 5% bone marrow blasts) with either:

Initial CR duration < 1 year
Prior unsuccessful salvage attempt or allogeneic HCT
2nd relapse or higher

OR

-Disease progression while on treatment with HMA+/-venetoclax for MDS/AML

Patients with a susceptible FLT3, IDH1 or IDH2 mutation should be resistant or intolerant to an agent targeting the specific mutation or otherwise be determined to be ineligible to receive a targeted agent by their treating physician.

Additional inclusion criteria for both cohorts are:

CD7 positive expression must be demonstrated in malignant cells in bone marrow, peripheral blood, or lymph node biopsies (fresh or archival) by Washington University Pathology lab. For both dose escalation and dose-expansion, any qualitative expression of CD7 will be permitted.
Age ≥ 18 years of age
Eastern Cooperative Oncology Group Performance Status ≤ 2

Adequate organ function as defined below:

Total bilirubin ≤ 2x ULN (unless the patient has Grade 1 bilirubin elevation due to Gilbert's disease or a similar syndrome involving slow conjugation of bilirubin).
AST(SGOT) and ALT(SGPT) ≤ 5x ULN
Creatinine within normal institutional limits OR creatinine clearance ≥ 30 mL/min/1.73 m2 by Cockcroft-Gault Formula
Oxygen saturation ≥ 90% on room air
Ejection fraction ≥ 40% confirmed by echocardiogram or MUGA
The effects of WU-CART-007 on the developing human fetus are unknown. For this reason, women of childbearing potential and male patients (along with their female partners) are required to use two forms of acceptable contraception, including one barrier method, during participation in the study and for 12 months following the last dose of WU-CART-007. Should a woman (or the female partner of a male patient) become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
Able to understand and willing to sign an IRB approved written informed consent document.
For AML patients, circulating blast count must be <30,000/µL by morphology or flow cytometry (cytoreductive therapies including leukapheresis or hydroxyurea are allowed as defined by protocol)
Patients must have no other effective standard of care therapy options, and patients must be unwilling or unable to travel to another site for treatment.

Exclusion Criteria:

Patients will be excluded from study entry for any of the following:

Received systemic anticancer therapy (including investigational therapy) or radiotherapy < 28 days or 5 half-lives, whichever is shorter, prior to the start of lymphodepleting chemotherapy with the exception of bridging treatment as defined by protocol.
Received any T-cell lytic or toxic antibody (e.g., alemtuzumab) within 8 weeks prior to lymphodepleting chemotherapy.

Subjects who have received a prior allogeneic HCT are excluded if any of the following criteria are present:

< 100 days post alloHCT
< 6 weeks from prior donor leukocyte infusion
Presence of acute or extensive chronic GVHD requiring systemic immunosuppression except for prednisone ≤ 10 mg or equivalent.
< 28 days from last dose of systemic immunosuppressive therapy (eg. calcineurin inhibitors, immunosuppressive antibodies, mycophenolate mofetil, ruxolitinib, ibrutinib) except for prednisone ≤ 10 mg or equivalent.
Previous treatment with any anti-CD7 directed therapy.
Known hypersensitivity to one or more of the study agents.
Active or latent Hepatitis B or active Hepatitis C without previous curative treatment.
Confirmed HIV infection.
History of concurrent second cancers requiring active, ongoing systemic treatment with the exception of adjuvant hormonal therapy for breast or prostate cancer.
Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum or urine pregnancy test at time of enrollment and within 7 days of starting lymphodepleting chemotherapy.
Serious active infection or another serious underlying medical condition that in the opinion of the treating physician would impair the ability of the patient to receive protocol treatment including, but not limited to symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia or serious, unstable neurologic symptoms.
Symptomatic, uncontrolled hypotension.