Neoplasms

Symptoms and General Pathology

All Conditions

Nervous System Diseases

Neoplasm Metastasis

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

All Drugs and Chemicals

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Dose Escalation phase (3+3 patients):

Pritumumab administered sequentially as 1-hour IV infusion, on Day 1, 8, and 22 of each 28-day treatment cycle at: 1.6 mg/kg, 4.8 mg/kg, 8.0 mg/kg, 12.0 mg/kg, and 16.2 mg/kg, for a maximum of 6 cycles or progression or unacceptable toxicity.

Expansion phase (6-12 patients): Pritumumab administered as 1-hour IV infusion, on Day 1, 8, and 22 of each 28-day treatment cycle at or below MTD for a maximum of 6 cycles or progression or unacceptable toxicity.

Pritumumab IgG1 human monoclonal antibody

Pritumumab

Laurie Hendricks, BSN, RN, OCN

Amy King, BSN, RN, CCR

Charles Redfern, MD

Jose A. Carrillo, MD

Pritumumab is a human IgG1 kappa antibody that binds to a malignant tumor associated antigen, ecto domain-vimentin (EDV) which is expressed in a variety of tumor cells. Pritumumab was shown to have relatively high reactivity with brain cancer cell lines, while no reactivity was demonstrated with normal neurons, astrocytes or fetal cerebral cells. Pritumumab has notable antibody-dependent cellular cytotoxicity (ADCC), brain tumor penetration and antitumor activity in nude mouse human xenograft models.

Primary Objectives

- To determine the safety and/or tolerability and the recommended Phase 2 dose (RP2D) of escalating, intravenously (IV) administered Pritumumab doses in patients with recurrent gliomas or with brain metastases.

Secondary Objectives

* To determine pharmacokinetics and pharmacodynamics of Pritumumab
* To identify preliminary signals of anti-tumor response to Pritumumab
* To explore disease-related, patient-reported outcomes

This is an open-label, Phase 1, outpatient, dose escalation study of Pritumumab in patients with brain cancer who have failed prior therapy and have no other available options. In the first part of the study, escalating doses of Pritumumab of 1.6, 4.8, 8.0, 12.0, and 16.2 mg/kg will be administered in a sequential, safety-driven manner to eligible patients according to standard 3+3 scheme, as an 1-hour IV infusion on Days 1, 8, 15, and 22 of each 28-day treatment cycle. The dose levels may be modified upon obtained results. Once the maximum tolerated dose (MTD) is determined, an expansion cohort including 6-12 patients in selected tumor type at a dose equal or below to MTD is planned to determine the recommended Phase 2 dose (RP2D). A total of 42 patients may be administered with Pritumumab in this study.

Patients will be treated with Pritumumab for a maximum of 6 cycles or until cancer progression or unacceptable toxicity. Patients will be followed after treatment completion every four months or until death or lost to follow-up. Standard clinical, laboratory and functional assessments will be employed to monitor for safety, tolerability and tumor response, including blood sampling for clinical biochemistries, pharmacokinetics, CSF and tissue samples, at frequency specified by the protocol. Patient-reported outcomes will also be assessed.

Open label, non-randomized, 3+3 dose escalation to determine MTD, followed by exoansion to 6-12 patients to determine RP2D. Subjects will continue study treatment until progressive disease or unacceptable toxicity. Follow-up will occur until death or lost to follow-up.

Safety Study of Pritumumab in Brain Cancer

A Phase 1, Sequential Cohort, Open-Label, Dose-Escalation Study of the Safety and CNS Exposure of Pritumumab in Patients With Brain Cancer

Number of participants with treatment-related adverse events as assessed by NCI-CTCAE v.5.0 during first 24 weeks of treatment

Intra-cranial objective response rate at 2 months as assessed by the Response Assessment in Neuro-oncology (RANO) criteria

Hoag Memorial Hospital Presbyterian

Nascent Biotech

Blood and Lymph Conditions

Immune System Diseases

Behaviors and Mental Disorders

Rare Diseases

Lymphoma

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Attention Deficit Disorder with Hyperactivity

Acute Disease

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Disease Attributes

Lymphosarcoma

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Childhood Acute Lymphoblastic Leukemia

Central Nervous System Stimulants

Cardiotonic Agents

Methylphenidate

Dopamine

Dopamine Uptake Inhibitors

Dopamine Agents

Neurotransmitter Agents

Administered 1 capsule each day for 1 week, .3 mg/kg dose.

Administered 1 capsule each day for 1 week.

1 capsule each day for 1 week, .3 mg/kg dose.

Placebo

Alicia Kunin-Batson, Ph.D.

While neurocognitive impairments in attention, memory and executive functioning are commonly reported sequelae of childhood leukemia and brain tumors, studies have only recently begun to examine the treatment of attention deficits in this population. Numerous studies have examined the effectiveness of methylphenidate in the treatment of children with attention deficit hyperactivity disorder (ADHD). However, the effectiveness of this medication for improving attention and behavioral functioning in children with medical illnesses or brain injury are less clear.

Patients will be randomized to receive one week of Metadate CD (a controlled release form of methylphenidate, similar to Ritalin) and one week of placebo in a double-blind fashion.

Effects of Methylphenidate on Attention Deficits in Childhood Cancer Survivors

Effects of Methylphenidate on Neuropsychological Functioning in Children With Attention Deficits Secondary to Childhood Cancer

Child performance on neuropsychological testing (i.e., using Test of Variables of Attention \[TOVA\] which is a computerized test of attention that assists in the screening, diagnosis, and treatment monitoring of attention disorders, like Attention Deficit Hyperactivity Disorder \[ADHD\], and working memory index of the WisSC IV. Standard scores average = 100 +/- 15. Higher scores indicate better performance. Scores \< or = 1 SD below the mean represent area of deficit.

Parent and teacher ratings of attention, executive function and behavior (i.e., Behavior Rating Inventory of Executive Function \[BRIEF -a parent questionnaire and a teacher questionnaire-designed to assess executive functioning in home and school environments. Conners Parent Rating Scale-3 Short Form \[CPRS-3 research and clinical tool for obtaining parental reports of childhood behavior problems.\] Standard scores average = 50 + or - 10. Higher scores indicate more severe difficulty. Scores \> or = 60 represent areas of significant behavior concern.

Children's Cancer Research Fund United States

University of Minnesota

No patients received treatment, therefore no adverse events were reported.

Participant previously had acute lymphoblastic leukemia or brain tumor to be treated with Methylphenidate or Placebo - Administered 1 capsule each day for 1 week, .3 mg/kg dose.

Participant With Attention Deficit

Age, Categorical

Sex: Female, Male

Only 1 patient was enrolled in this study, no analysis/outcome data can be reported. This patient completed baseline assessment, but withdrew from the study before beginning the medication trial. No medications/placebo were administered.

Alicia Kunin-Batson

No patients received treatment, therefore analysis was not done.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Safety Study of Pritumumab in Brain Cancer	NCT04396717	Malignant Prima... Brain Metastase...	Pritumumab	18 Years -	Nascent Biotech
Safety Study of Pritumumab in Brain Cancer	NCT04396717	Malignant Prima... Brain Metastase...	Pritumumab	18 Years -	Nascent Biotech
Effects of Methylphenidate on Attention Deficits in Childhood Cancer Survivors	NCT01100658	ALL, Childhood Leukemia, Lymph... Leukemia, Lymph... Leukemia, Lymph... Leukemia, Lymph... Leukemia, Lymph... Leukemia, Lymph... Leukemia, Lymph... Leukemia, Lymph... Lymphoblastic L... Lymphoblastic L... Lymphoblastic L... Lymphoblastic L... Lymphoblastic L... Lymphoblastic L... Lymphocytic Leu... Lymphocytic Leu... Lymphocytic Leu... Brain Tumors Cancer of the B... Cancer of Brain Malignant Prima... Brain Neoplasms...	Methylphenidate Placebo	8 Years - 17 Years	University of Minnesota
Effects of Methylphenidate on Attention Deficits in Childhood Cancer Survivors	NCT01100658	ALL, Childhood Leukemia, Lymph... Leukemia, Lymph... Leukemia, Lymph... Leukemia, Lymph... Leukemia, Lymph... Leukemia, Lymph... Leukemia, Lymph... Leukemia, Lymph... Lymphoblastic L... Lymphoblastic L... Lymphoblastic L... Lymphoblastic L... Lymphoblastic L... Lymphoblastic L... Lymphocytic Leu... Lymphocytic Leu... Lymphocytic Leu... Brain Tumors Cancer of the B... Cancer of Brain Malignant Prima... Brain Neoplasms...	Methylphenidate Placebo	8 Years - 17 Years	University of Minnesota

Spots Global Cancer Trial Database for malignant primary brain tumors