Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04512716
Recruitment Status : Not yet recruiting
First Posted : August 13, 2020
Last Update Posted : October 5, 2020
Sponsor:
Collaborator:
Actinium Pharmaceuticals
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Brief Summary:
This is a single-cohort pilot study; patients will receive 131-I apamistamab 75 mCi prior to CAR T-cell infusion in order to determine the maximum tolerated dose of 131-I apamistamab.

Condition or disease Intervention/treatment Phase
B-ALL DLBCL B ALL Dlbcl-Ci DLBCL Unclassifiable DLBCL, Nos Genetic Subtypes DLBCL Activated B-Cell Type DLBCL Germinal Center B-Cell Type Diffuse Large B-cell Lymphoma HGBL HGBL, Nos Drug: 131-I Apamistamab Biological: CAR T-cell Early Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 6 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Estimated Study Start Date : October 2020
Estimated Primary Completion Date : August 2021
Estimated Study Completion Date : August 2021


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
Drug: 131-I Apamistamab
Patients will receive 131-I apamistamab 75 mCi 5-7 days prior to a single infusion of 1x106 19-28z CAR T-cells/kg. 131-I apamistamab may be administered inpatient or outpatient at the discretion and judgment of the treating investigators.
Other Name: Iomab-B

Biological: CAR T-cell
19-28z CAR T-cells will be administered inpatient as a single infusion of 1x106 19-28z CAR T-cells/kg, for those in the B-ALL cohort, or 2x106 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).




Primary Outcome Measures :
  1. 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 75 mCi 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

ii. Patients must have at least one FDG-avid (PET-avid) measurable lesion iii. Biopsy confirmation of relapsed of refractory DLBCL is required 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

  • 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 ≤ 2.0 mg/dL
  • 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:

    1. Absolute neutrophil count ≥0.5k/µL,
    2. Platelets ≥30k/µL,
    3. 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:

    1. New York Heart Association (NYHA) stage III or IV congestive heart failure
    2. Myocardial infarction ≤6 months prior to enrollment
    3. Any history of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration
    4. 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:

    1. 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.
    2. 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 in Section 6.1, without known development of an exclusion criterion in Section 6.2, prior to proceeding to 131-I apamistamab infusion. See Section 9.2 re: screening for treatment.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04512716


Contacts
Layout table for location contacts
Contact: Mark B Geyer, MD 646-608-3745 geyerm@mskcc.org
Contact: Neeta Pandit-Taskar, MD 212-639-3046 pandit-n@mskcc.org

Locations
Layout table for location information
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Contact: Mark B Geyer, MD    646-608-3745    geyerm@mskcc.org   
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Actinium Pharmaceuticals
Investigators
Layout table for investigator information
Principal Investigator: Mark B Geyer, MD Memorial Sloan Kettering Cancer Center
Additional Information:
Layout table for additonal information
Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT04512716    
Other Study ID Numbers: 20-382
First Posted: August 13, 2020    Key Record Dates
Last Update Posted: October 5, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Memorial Sloan Kettering Cancer Center:
CD19+ B-cell malignancy
131-I apamistamab
B-cell malignancy
Memorial Sloan Kettering Cancer Center
Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia
Leukemia, Lymphoid
Lymphoma, Non-Hodgkin