Combination Veltuzumab and Fractionated 90Y- Epratuzumab Radioimmunotherapy in Follicular Lymphoma

NCT01147393 | Terminated Phase 1 Results DMC

• 1 other identifier: 1001010838
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

A Phase I/II clinical trial using a fractionated dosing regimen of 90Y-epratuzumab (anti-CD22) has showed encouraging responses in follicular and aggressive NHL with an ability to administer safely 2 injections of 20 mCi/m2 spaced 1 week apart. The investigators propose to combine this active 90Y-epratuzumab treatment with a regimen of veltuzumab that was also found active in Phase I/II trials. The goal of this study is to determine the safety and efficacy of 90Y-epratuzumab when used in combination with veltuzumab. The primary objective is to determine the response rate of this combination treatment. Secondary objectives are to assess safety, pharmacokinetics and targeting of 90Y-epratuzumab . Veltuzumab blood levels and anti-antibody responses will also be monitored at various times.

Conditions

Follicular Lymphoma

Outcome Measures

Primary Outcomes (4)

• Determine the Maximum Tolerated 90Y Dose

• Dose-limiting Toxicity

  NCI CTC version 3.0 is used to grade all adverse events and to provide management guidelines for infusional toxicity. Dose-limiting toxicity (DLT) is defined as follows: Hematologic: Grade 4 toxicity \>7 days, as specified by hemoglobin levels, platelet counts or absolute neutrophil count (ANC) or failure of hemoglobin levels, platelet counts or ANC to recover to Grade 1 levels within 12 weeks of completing the treatment cycle (with the use of RBC and platelet transfusions or growth factors during the 12 weeks if necessary, but at least one week without any support prior to qualifying Grade 1 levels). Non-Hematologic: Any Grade 3 or Grade 4. Other: Any Grade 2 autoimmune reactions, or the occurrence of Grade 2 immediate-type allergic/hypersensitivity reactions (e.g., urticaria, wheezing, hypoxia and dyspnea) will be considered DLT and will also require the infusion to be permanently terminated. Occurrence of DLT requires a patient's treatment to be permanently discontinued

• Safety

• The Primary Objective of the Phase II Portion of the Study is to Determine the Anti-tumor Efficacy, as Measured by Response Rate, of Fractionated 90Y-epratutumab IgG Given in Combination With Veltuzumab Anti-CD20 IgG Therapy

Study Arms (1)

All subjects

EXPERIMENTAL

two weekly infusions of 90Y-epratuzumab tetraxetan in combination with four weekly infusions of 200 mg/m2 veltuzumab.

Drug: 90Y-epratuzumab tetraxetan; Biological: veltuzumab

Interventions

90Y-epratuzumab tetraxetan DRUG

The 90Y-epratuzumab treatment will begin one week after the 4th veltuzumab injection. Patients will receive unlabeled, unconjugated epratuzumab (1.5 mg/kg) that will be infused over \~30 minutes. All patients will then receive a 90Y-epratuzumab dose. Dose will be escalated by patient cohort either at 15 mCi/m2 or 20 mCi/m2. The second 90Y-epratuzumab treatment will be given at the same dose, 1 week after the first 90Y-epratuzumab dose.

All subjects

veltuzumab BIOLOGICAL

Veltuzumab is given in 4 weekly doses, each 200 mg/m2.

All subjects

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, \>18 years old
• Histological diagnosis of CD20+ Follicular lymphoma by WHO lymphoma criteria.
• FLIPI intermediate or high risk (2-5 risk factors)
• No prior systemic treatment for NHL
• Measurable disease by CT, with at least one lesion \>1.5 cm in one dimension
• Life expectancy of at least 6 months
• ECOG performance status \> = 2
• Patients must have normal organ and marrow function as defined below:
• ANC \> = 1,500/uL
• platelets \> = 100,000/uL
• total bilirubin \< = 1.5 x upper limit of normal
• AST(SGOT)/ALT(SGPT) \< = 2.5 X upper limit of normal
• creatinine \< = 1.5 x upper limit of normal
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Pregnant or lactating women. Women of childbearing potential are required to have a negative pregnancy test
• Women of childbearing potential and fertile men who are not practicing or who are unwilling to practice birth control while enrolled in the study until at least 12 weeks after the last weekly veltuzumab infusion.
• Primary CNS lymphoma, HIV lymphoma or transformed lymphoma, or presence of symptomatic CNS metastases or carcinomatous meningitis.
• Bulky disease by CT, defined as any single mass \>10 cm in its greatest diameter
• Disease status eligible for potentially curative external beam radiation (stage 1 or contiguous stage 2 at sites appropriate for radiotherapy)
• Bone marrow involvement ≥25%; patients with CLL
• Pleural effusion with positive cytology for lymphoma
• Patients known to be HIV positive or hepatitis B positive
• Corticosteroid use within 2 weeks, unless 20 mg/day or less at stable dose.
• Prior malignancy with less than a 1-year disease-free interval, excluding non-melanoma skin cancers and carcinoma in situ of the cervix.
• Other concurrent medical or psychiatric conditions that, in the Investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Gilead Sciences: collaborator

Study Sites (1)

Weill Cornell Medical College

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Lymphoma, Follicular

Interventions

veltuzumab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Peter Martin, MD
• Organization: Weill Cornell Medicine

amr2017@med.cornell.edu

646.962.2064

Study Officials

• Peter Martin, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2010
• First Posted: June 22, 2010
• Study Start: October 1, 2010
• Primary Completion: August 6, 2013
• Study Completion: July 31, 2015
• Last Updated: February 22, 2018
• Results First Posted: June 2, 2017

Record last verified: 2018-01

Locations

US (1)