- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04512716
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
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Estimated)
Phase
- Early Phase 1
Contacts and Locations
Study Contact
- Name: Mark B Geyer, MD
- Phone Number: 646-608-3745
- Email: geyerm@mskcc.org
Study Contact Backup
- Name: Neeta Pandit-Taskar, MD
- Phone Number: 212-639-3046
- Email: pandit-n@mskcc.org
Study Locations
-
-
New Jersey
-
Basking Ridge, New Jersey, United States, 07920
- Recruiting
- Memorial Sloan Kettering at Basking Ridge (Limited Protocol Activities)
-
Contact:
- Mark Geyer, MD
- Phone Number: 646-608-3745
-
Middletown, New Jersey, United States, 07748
- Recruiting
- Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
-
Contact:
- Mark Geyer, MD
- Phone Number: 646-608-3745
-
Montvale, New Jersey, United States, 07645
- Recruiting
- Memorial Sloan Kettering Bergen (Limited Protocol Activities)
-
Contact:
- Mark Geyer, MD
- Phone Number: 646-608-3745
-
-
New York
-
Commack, New York, United States, 11725
- Recruiting
- Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)
-
Contact:
- Mark Geyer, MD
- Phone Number: 646-608-3745
-
Harrison, New York, United States, 10604
- Recruiting
- Memorial Sloan Kettering Westchester (Limited Protocol Activities)
-
Contact:
- Mark Geyer, MD
- Phone Number: 646-608-3745
-
New York, New York, United States, 10065
- Recruiting
- Memorial Sloan Kettering Cancer Center
-
Contact:
- Mark B Geyer, MD
- Phone Number: 646-608-3745
- Email: geyerm@mskcc.org
-
Rockville Centre, New York, United States, 11553
- Recruiting
- Memorial Sloan Kettering Nassau (Limited Protocol Activites)
-
Contact:
- Mark Geyer, MD
- Phone Number: 646-608-3745
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Patients with B-ALL or DLBCL (or subtypes thereof) who have relapsed or refractory disease will be eligible. Refractory disease is defined by failure to achieve at least a partial response or disease progression within 6 months of the last therapy. Patients who initially respond but subsequently demonstrate disease progression are considered to have relapsed disease
Participant Inclusion Criteria:
- 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.
Participant Exclusion Criteria:
- ECOG performance status ≥3.
- Pregnant or lactating patients. Patients of childbearing age should use effective contraception while on this study and continue for 1 year after all treatment is finished.
- Impaired cardiac function (LVEF <40%) as assessed by echocardiogram or MUGA scan during screening
- Patients with active graft versus host disease following allogeneic hematopoietic cell transplantation requiring systemic T-cell suppressive therapy are ineligible
- Patients with active autoimmune disease requiring systemic T-cell suppressive therapy are ineligible
Patients with following cardiac conditions will be excluded:
- New York Heart Association (NYHA) stage III or IV congestive heart failure
- Myocardial infarction ≤6 months prior to enrollment
- Any history of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration
- Any history of severe non-ischemic cardiomyopathy with LVEF ≤20%
Have current or prior positive test results for human immunodeficiency virus (HIV) or hepatitis B (HBV) or C (HCV), with the following exceptions:
- Subjects who have positive HBV test results due to having been previously vaccinated against hepatitis B, as evidenced by negative hepatitis B surface antigen (HBsAg), negative anti- hepatitis B core protein (HBc) and positive antibody to the HBsAg (anti-HBs) are not excluded.
- Subjects who have antibodies to HCV or who have hepatitis B core antibody, with undetectable viremia by PCR, and with adequate organ function as defined in the protocol, are not excluded.
- Patients with uncontrolled systemic fungal, bacterial, viral or other infection are ineligible.
- Patients with any concurrent active malignancies as defined by malignancies requiring any therapy other than expectant observation or hormonal therapy, with the exception of squamous and basal cell carcinoma of skin.
- Patients with history or presence of clinically significant neurological disorders such as epilepsy, generalized seizure disorder, severe brain injuries are ineligible.
- Any other issue which, in the opinion of the treating physician, would make the patient ineligible for the study.
- Patients with circulating human anti-mouse antibodies to BC8 noted on initial screening (see Appendix III)
Subject Inclusion Criteria for 131-I Apamistamab Infusion Patients should meet performance status and organ function parameters as specified, without known development of an exclusion criterion, prior to proceeding to 131-I apamistamab infusion. See Section 9.2 re: screening for treatment.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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
|
19-28z CAR T-cells will be administered inpatient as a single infusion of 1x10^6 19-28z CAR T-cells/kg, for those in the B-ALL cohort, or 2x10^6 19-28z CAR T-cells/kg, for those in the DLBCL cohort.
Patients will be observed inpatient for a minimum of 7 days (longer as clinically indicated and at the discretion of the treating physician).
Patients will receive 131-I apamistamab 5-7 days prior to a single infusion of 1x10^6 19-28z CAR T-cells/kg for those in the B-ALL cohort, or 2x10^6 19-28z CAR T-cells/kg, for those in the DLBCL.
131-I apamistamab may be administered inpatient or outpatient at the discretion and judgment of the treating investigators.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Dose-limiting toxicities and maximum tolerated dose of 131-I apamistamab, when given in combination with 19-28z CAR T-cells for treatment of relapsed or refractory B-cell ALL or DLBCL
Time Frame: 30 days after treatment
|
To determine the safety and tolerability of a single dose of 131-I apamistamab given prior to 19-28z CAR T-cell infusion in patients with relapsed or refractory B-cell ALL or DLBCL.
|
30 days after treatment
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Mark B Geyer, MD, Memorial Sloan Kettering Cancer Center
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma, Non-Hodgkin
- Hematologic Diseases
- Leukemia, Lymphoid
- Leukemia
- Lymphoma
- Lymphoma, B-Cell
- Lymphoma, Large B-Cell, Diffuse
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
Other Study ID Numbers
- 20-382
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Diffuse Large B-cell Lymphoma
-
Memorial Sloan Kettering Cancer CenterRecruitingLymphoma | Lymphoma, B-Cell | DLBCL - Diffuse Large B Cell Lymphoma | Large B-cell Lymphoma | Large-cell Lymphoma | Mediastinal B-Cell Diffuse Large Cell LymphomaUnited States
-
Roswell Park Cancer InstituteNational Cancer Institute (NCI); AmgenActive, not recruitingRecurrent Diffuse Large B-Cell Lymphoma | Refractory Diffuse Large B-Cell Lymphoma | CD20 Positive | Stage I Diffuse Large B-Cell Lymphoma | Stage II Diffuse Large B-Cell Lymphoma | Stage III Diffuse Large B-Cell Lymphoma | Stage IV Diffuse Large B-Cell LymphomaUnited States
-
Qian WenbinNot yet recruitingDiffuse Large B Cell Lymphoma | Refractory Diffuse Large B-Cell Lymphoma | Relapsed Diffuse Large B-Cell LymphomaChina
-
University Hospital Southampton NHS Foundation...Hoffmann-La RocheTerminatedDiffuse Large B Cell Lymphoma | Refractory Diffuse Large B-Cell Lymphoma | Relapsed Diffuse Large B-Cell LymphomaUnited Kingdom
-
National Cancer Institute (NCI)WithdrawnDiffuse, Large B-cell Lymphoma | Lymphoma, Diffuse Large-Cell | Lymphoma, Diffuse Large-Cell B-cell | Large-Cell Lymphoma, Diffuse
-
Dana-Farber Cancer InstituteBayer; AbbVieActive, not recruitingDiffuse Large B Cell Lymphoma | Refractory Diffuse Large B-Cell Lymphoma | Relapsed Diffuse Large B-Cell LymphomaUnited States
-
Memorial Sloan Kettering Cancer CenterSanofi; Columbia University; Medical College of Wisconsin; University of Rochester and other collaboratorsActive, not recruitingDiffuse Large B-cell Lymphoma (DLBCL) | Relapsed Diffuse Large B-cell Lymphoma (DLBCL) | Refractory Diffuse Large B-cell Lymphoma (DLBCL)United States
-
Autolus LimitedCompletedDiffuse Large B Cell Lymphoma | Refractory Diffuse Large B-Cell Lymphoma | DLBCL | Relapsed Diffuse Large B-Cell LymphomaUnited States, United Kingdom
-
Herlev HospitalOdense University Hospital; Zealand University Hospital; Aarhus University Hospital and other collaboratorsCompletedDiffuse Large B-cell Lymphoma Recurrent | Diffuse Large B Cell Lymphoma | Diffuse Large B-Cell Lymphoma Cell of Origin
-
UNC Lineberger Comprehensive Cancer CenterCephalonCompletedLymphoma | Diffuse Large B-Cell Lymphoma | Lymphoma, Diffuse Large-Cell | Diffuse Large-Cell LymphomaUnited States
Clinical Trials on CAR T-cell
-
Beijing GoBroad HospitalRecruitingAcute Lymphoblastic Leukemia, in Relapse | Refractory Acute Lymphoblastic Leukemia | T-cell Acute Lymphoblastic LeukemiaChina
-
City of Hope Medical CenterNational Cancer Institute (NCI); California Institute for Regenerative Medicine...RecruitingBreast Cancer | HER2-positive Breast Cancer | Malignant Neoplasm | Metastatic Malignant Neoplasm in the Brain | Metastatic Malignant Neoplasm in the LeptomeningesUnited States
-
Bellicum PharmaceuticalsSuspendedHER2-positive Breast Cancer | HER2-positive Gastric Cancer | Solid Tumor, Adult | HER-2 Gene Amplification | HER-2 Protein OverexpressionUnited States
-
Fudan UniversityGuangzhou Bioresette Biomedical Technology Co., Ltd.; Chaosu Hu,Principal Investigator...RecruitingNasopharyngeal CarcinomaChina
-
The Affiliated Hospital of Xuzhou Medical UniversityXuzhou Medical UniversityRecruiting
-
Memorial Sloan Kettering Cancer CenterWithdrawnLymphoma | Lymphoma, B-Cell | LeukemiaUnited States
-
Fuda Cancer Hospital, GuangzhouWithdrawnCAR-T Cell Immunotherapy | GPC3 Positive Hepatocellular CarcinomaChina
-
Hebei Senlang Biotechnology Inc., Ltd.RecruitingLymphoma | Multiple Myeloma | Acute Lymphoblastic LeukemiaChina
-
Zhu XiaofanRecruitingB Lymphoblastic Lymphoma | B Lymphocytic LeukemiaChina
-
The Affiliated Hospital of Xuzhou Medical UniversityRecruitingAcute T-lymphoblastic Leukemia | Acute T-lymphoblastic LymphomaChina