Dose-escalation and Dose-expansion Study of Safety of Azer-cel (PBCAR0191) in Participants With Relapsed/Refractory (r/r) Non-Hodgkin Lymphoma (NHL) and r/r B-cell Acute Lymphoblastic Leukemia (B-ALL)

Summary

This is a Phase 1/1b, nonrandomized, open-label, parallel assignment, dose-escalation, and dose-expansion study to evaluate the safety and clinical activity of azer-cel, an allogeneic anti-CD19 CAR T, in adults with r/r B ALL, r/r B-cell NHL and CLL/SLL.

Eligibility

Key Inclusion Criteria

Criteria for B-ALL:

• Participant has confirmed unequivocal r/r CD19+ B-ALL.

Criteria for NHL and CLL/SLL:

• Participant has unequivocal aggressive CD19+ r/r B-cell NHL that is confirmed by tumor biopsy tissue from last relapse after CD19-directed therapy.

For Phase 1 Dose Escalation:

* Diffuse large B-cell lymphoma (DLBCL) including Richter's transformation
* Follicular lymphoma (FL) including Grade 3 or transformed FL
* High-grade B-cell lymphoma (HGBCL)
* Primary mediastinal lymphoma

For Phase 1b Dose Expansion (CAR T-relapsed cohort):

* DLBCL not otherwise specified (NOS)
* HGBCL
* DLBCL transformed from the following indolent lymphoma subtypes (FL, Marginal Zone lymphoma \[MZL\], and Waldenstrom's Macroglobulinemia \[WM\])
* Other large B-cell lymphoma (LBCL) subtypes may be enrolled with approval from the Medical Monitor.
* Participants previously treated with CD19-directed autologous CAR T therapies have received no more than 2 lines of therapy after administration of their previous CAR T product.
* For the expansion CAR T-relapsed cohort only: Participants must have received autologous CD19-directed CAR T therapy and demonstrated clinical response to the treatment at Day 28 or later, followed by relapse or progression.

For Phase 1b dose expansion (CAR T-naive cohort):

* DLBCL NOS
* DLBCL transformed from the following indolent lymphoma subtypes (FL, MZL, and WM)
* HGBCL
* FL (Grade 1-3a)
* MZL that is fluorodeoxyglucose (FDG)-avid on positron emission tomography (PET) scan
* WM
* CLL/SLL
* Primary central nervous system (CNS) lymphoma (PCNSL)
* Other LBCL subtypes may be enrolled with approval from the Medical Monitor.
* Participant must have received at least 1-2 prior lines of therapy, depending on histological subtype but no more than 7 systemic lines of anti-cancer therapy.

Criteria for both B-ALL, NHL, and CLL/SLL:

* Eastern Cooperative Oncology Group performance status score of 0 or 1.
* An estimated life expectancy of at least 12 weeks according to the investigator's judgment.
* Seronegative for human immunodeficiency virus antibody.
* Participant has adequate bone marrow, renal, hepatic, pulmonary, and cardiac function.

Key Exclusion Criteria

Criteria for B-ALL:

• Burkitt cell (L3 ALL) or mixed-lineage acute leukemia.

Criteria for NHL:

* Requirement for urgent therapy due to tumor mass effects such as bowel obstruction or blood vessel compression.
* Active hemolytic anemia.

Criteria for B-ALL and NHL:

* No active CNS disease, excluding PCNSL
* History of another primary malignancy
* Any form of primary immunodeficiency (for example, severe combined immunodeficiency disease).
* History of hepatitis B or hepatitis C currently receiving ongoing antiviral therapy.

Any known uncontrolled cardiovascular disease at the time of Screening that, in the investigator's opinion, renders the participant ineligible

* History of hypertension crisis or hypertensive encephalopathy within 3 months prior to Screening.
* History of severe immediate hypersensitivity reaction to any of the agents used in this study.
* Presence of a CNS disorder that, in the opinion of the investigator, renders the participant ineligible for treatment.
* History of concomitant genetic syndrome such as Fanconi anemia, Kostmann syndrome, Shwachman-Diamond syndrome, or any other known bone marrow failure syndrome.
* Active uncontrolled autoimmune disease requiring active immunosuppression at the time of Screening (excluding participants needing steroids for physiologic replacement).
* Participant has received stem cell transplant within 90 days before Screening.
* Participant has active graft-versus-host disease (GvHD) symptoms.
* Participant has received a systemic biologic agent for treatment of the disease under study within 28 days of LD, other systemic anti-cancer therapy within 10 days or 5 half-lives (whichever is shorter) of LD, and no pulse steroid for disease control within 3 days of LD.
* Radiotherapy within 4 weeks before Screening.
* Presence of pleural/peritoneal/pericardial catheter, as well as permeant biliary and ureteral stents (does not apply to intravenous lines).
* Participant has received live vaccine within 4 weeks before Screening. Note: Non-live virus vaccines are not excluded.
* Participant has received CD19-directed therapy other than autologous CD19-directed CAR T therapy within 90 days of the anticipated start date of LD.

Additional criteria apply.

Conditions5

Locations18 sites

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