CAR T-cell Therapy in Patients With Renal Dysfunction

Study Overview
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Brief Summary
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This is a prospective, descriptive study designed to assess the feasibility of administering CAR T therapy among patients with moderate to severe renal impairment using dose adjusted lymphodepleting chemotherapy.

Official Title
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Lymphodepleting Chemotherapy With Fludarabine and Cyclophosphamide Prior to Infusion of CAR T Cell Therapy in Patients With Moderate-Severe Renal Dysfunction

Conditions
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Non-hodgkin Lymphoma,B Cell, Multiple Myeloma, Acute Lymphoblastic Leukemia, Adult

Intervention / Treatment
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* Drug: Fludarabine
* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Receiving lymphodepleting chemotherapy prior to commercial CAR-T administration for multiple myeloma, leukemia, or lymphoma Adequate bone marrow function to receive lymphodepleting chemotherapy Renal function </= 60mL/min/1.73m2 ECOG 0-2 Exclusion Criteria: Relative CNS disorders Active uncontrolled infection or any other concurrent disease or medical condition that was deemed to interfere with the conduct of the study as judged by the investigator Use of therapeutic dose systemic corticosteroids (defined as >20mg/day prednisone or equivalent) within 72 hours of CAR-T administration

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Moderate Renal Dysfunction<br>Moderate renal dysfunction will receive a 20% dose reduction of fludarabine and no dose reduction for cyclophosphamide. | Drug: Fludarabine<br>* Received IV on Days -5 to -3 before CAR T cell therapy<br>Drug: Cyclophosphamide<br>* Received IV on Days -5 to -3 before CAR T cell therapy<br>|
| Experimental: Severe Renal Dysfunction<br>Several renal dysfunction will receive a 40% dose reduction of fludarabine and no dose reduction for cyclophosphamide. | Drug: Fludarabine<br>* Received IV on Days -5 to -3 before CAR T cell therapy<br>Drug: Cyclophosphamide<br>* Received IV on Days -5 to -3 before CAR T cell therapy<br>|
| Experimental: Dialysis Participants<br>Participants on dialysis will receive a 50% dose reduction of fludarabine and a 25% dose reduction of cyclophosphamide. | Drug: Fludarabine<br>* Received IV on Days -5 to -3 before CAR T cell therapy<br>Drug: Cyclophosphamide<br>* Received IV on Days -5 to -3 before CAR T cell therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of CRS | Collection of maximum grade of CRS (based on CTCAE v5) and when this event occurs post CAR T cell therapy infusion | 90 days | 
| Occurrence of ICANS | Collection of maximum grade of ICANs (based on CTCAE v5) and when this event occurs after CAR T cell therapy infusion | 90 days | 
| Occurrence of Cytopenias | Collection of grade 3 or higher (based on CTCAE v5) cytopenias not resolved by Day 30 post CAR T cell infusion | 90 days |