Iomab-ACT: A Pilot Study of 131-I Apamistamab Followed by CD19-Targeted CAR T-Cell Therapy for Patients With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia or Diffuse Large B-Cell Lymphoma

Who is this study for? Patients with relapsed or refractory B-cell acute lymphoblastic leukemia or diffuse large B-cell lymphoma
What treatments are being studied? 131-I Apamistamab+CAR T-cell
Status: Recruiting
Location: See all (7) locations...
Intervention Type: Biological, Drug
Study Type: Interventional
Study Phase: Early Phase 1
SUMMARY

This is a pilot study; patients will receive 131-I apamistamab prior to CAR T-cell infusion in order to determine the maximum tolerated dose of 131-I apamistamab is exceeded at 75 mCi, and if so, to assess the safety of a step-down dose of 50 mCi.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

∙ \- To be eligible for leukapheresis, patients must have a CD19+ B-cell malignancy with relapsed or refractory disease, defined below. To be eligible for 131-I apamistamab conditioning and treatment with 19-28z CAR T-cells, patients must additionally have detectable evidence of residual malignancy at the time of assessment prior to CAR T-cell infusion (as defined below), regardless of therapy administered following leukapheresis.

∙ a. Patients with diffuse large B-cell lymphoma (de novo or DLBCL transformed from an indolent lymphoma (follicular lymphoma, chronic lymphocytic leukemia \[Richter syndrome\]) or high-grade B-cell lymphoma (HGBL): (DLBCL patients) i. Defined as relapsed or refractory DLBCL or high-grade B-cell lymphoma (HGBL) following 2 or more prior chemoimmunotherapy regimens (with at least one course including an anthracycline and CD20-directed therapy) following diagnosis of de novo DLBCL/HGBL or DLBCL arising from indolent lymphoma, and requiring further treatment. Exception: patients with Richter syndrome (DLBCL arising from CLL/small lymphocytic lymphoma) are eligible following 1 or more prior chemoimmunotherapy regimens (with at least one course including an anthracycline and CD20-directed therapy) and do not require a second course of chemoimmunotherapy to be eligible.

∙ ii. Patients must have at least one FDG-avid (PET-avid) measurable lesion iii. Biopsy confirmation of relapsed of refractory DLBCL is required iv. For patients who have received treatment for confirmed relapsed or refractory disease otherwise meeting criteria a.i.-a.iii. as above, within 6 weeks of study enrollment, active disease does not need to be re-confirmed or present immediately prior to Screening A for the patient to be eligible for leukapheresis. However, detectable evidence of residual malignancy must be present at Screening B in order for the patient to be eligible for 131-I apamistamab and CAR T-cell therapy.

∙ b. Patients with B-cell acute lymphoblastic leukemia or B lymphoblastic lymphoma (ALL) or chronic myeloid leukemia (CML) in lymphoid blast crisis: (B-ALL patients) i. Patients with Philadelphia chromosome-negative B-cell ALL must have been refractory to at least 1 line of multi-agent chemotherapy or relapsed following at least 1 prior multiagent systemic chemotherapy regimen that included induction and consolidation therapy ii. Patients with Philadelphia chromosome-positive ALL or CML in lymphoid blast crisis must have exhibited persistent disease following therapy with a second- or third-generation tyrosine kinase inhibitor iii. Patients must have ≥5% bone marrow involvement and/or at least one FDG-avid (PET-avid) measurable extramedullary lesion iv. For patients who have received treatment for confirmed relapsed or refractory disease otherwise meeting criteria b.i.-b.iii. as above, within 6 weeks of study enrollment, active disease does not need to be re-confirmed or present immediately prior to Screening A for the patient to be eligible for leukapheresis. However, detectable evidence of residual malignancy must be present at Screening B in order for the patient to be eligible for 131-I apamistamab and CAR T-cell therapy.

• While prior CD19-targeted therapies, including CAR T-cell therapy, do not exclude participation, CD19 expression by immunohistochemical staining or flow cytometry must be confirmed prior to enrollment.

• Age ≥ 18 years of age

• Creatinine clearance ≥50 mL/min as calculated by the Cockroft-Gault formula

• Direct bilirubin ≤2.0 mg/dL, AST and ALT ≤3.0x upper limit of normal (ULN), unless liver dysfunction is thought to be related to underlying malignancy

• Adequate pulmonary function as assessed by ≥92% oxygen saturation on room air by pulse oximetry.

• Adequate bone marrow function meeting the following criteria as defined below, without requiring blood product or granulocyte-colony stimulating factor support in the past 7 days, unless cytopenias are attributed to underlying malignancy in the opinion of the investigator:

‣ Absolute neutrophil count ≥0.5k/µL,

⁃ Platelets ≥30k/µL,

⁃ Hemoglobin ≥7g/dL.

• ECOG performance status 0-2.

Locations
United States
New Jersey
Memorial Sloan Kettering at Basking Ridge (Limited Protocol Activities)
RECRUITING
Basking Ridge
Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
RECRUITING
Middletown
Memorial Sloan Kettering Bergen (Limited Protocol Activities)
RECRUITING
Montvale
New York
Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)
RECRUITING
Commack
Memorial Sloan Kettering Westchester (Limited Protocol Activities)
RECRUITING
Harrison
Memorial Sloan Kettering Cancer Center
RECRUITING
New York
Memorial Sloan Kettering Nassau (Limited Protocol Activites)
RECRUITING
Rockville Centre
Contact Information
Primary
Mark B Geyer, MD
geyerm@mskcc.org
646-608-3745
Backup
Somali Gavane, MD
212-639-2403
Time Frame
Start Date: 2021-02-02
Estimated Completion Date: 2026-01
Participants
Target number of participants: 12
Treatments
Experimental: B-Cell Acute Lymphoblastic Leukemia/Diffuse Large B-Cell Lym
Participants will have relapsed or refractory B-Cell Acute Lymphoblastic Leukemia or Diffused Large B-Cell Lymphoma
Sponsors
Leads: Memorial Sloan Kettering Cancer Center

This content was sourced from clinicaltrials.gov

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