Veltuzumab and Milatuzumab in Treating Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma
A Phase I/II Study of Veltuzumab (IMMU-106, hA20), a Humanized Anti-CD20 Monoclonal Antibody, Combined With Milatuzumab (IMMU-115, hLL1), a Humanized Anti-CD74 Monoclonal Antibody, in Relapsed and Refractory B-cell Non-Hodgkin's Lymphoma
2 other identifiers
interventional
35
1 country
1
Brief Summary
A phase I dose escalation study of veltuzumab and milatuzumab in relapsed and refractory B-cell NHL. The phase I study will be followed by a pilot phase II study.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1 lymphoma
Started Sep 2009
Typical duration for phase_1 lymphoma
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 1, 2009
CompletedFirst Submitted
Initial submission to the registry
October 2, 2009
CompletedFirst Posted
Study publicly available on registry
October 5, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
September 1, 2015
CompletedResults Posted
Study results publicly available
February 6, 2017
CompletedFebruary 6, 2017
December 1, 2016
5.6 years
October 2, 2009
April 28, 2016
December 8, 2016
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Dose Limiting Toxicity (DLT) for Phase I Patients
Dose-limiting toxicity was assessed during induction therapy for phase I.
up to 2 years
Maximum Tolerated Dose (MTD)for Phase I Patients
Patients received a fixed dose of Veltuzumab IV 200 mg/m2 and Milatuzumab was dose escalated
up to 2 years
Overall Objective Response Rate
Per International Response Criteria (Cheson JCO 2007) for target lesions and assessed by CT, MRI or PET: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses; Overall Response (OR) = CR + PR.
Up to 2 years
Secondary Outcomes (6)
Progression-free Survival (PFS)
up to 2 years
Fcγ-receptor Polymorphism Response to Treatment
up to 2 years
Quantitative T-, B-, and NK-cell Subsets Using Flow Cytometry
up to 1 year
Access Pharmacokinetics Through AUC0-∞ (Area Under Curve)
0, 24, 48, 72, 96 and 120 hours post-does
Access Pharmacokinetics Through Cmax
0, 24, 48, 72, 96 and 120 hours post-dose
- +1 more secondary outcomes
Study Arms (2)
Phase I
EXPERIMENTALPhase I portion of the study, a standard 3+3 dose escalation schema will be followed. Patients will receive veltuzumab IV weekly on day 1 for 4 doses and milatuzumab weekly on for 4 total doses during induction therapy. Induction therapy will be defined as the first 4 weeks of study therapy. During week 1 of induction therapy, patients will receive veltuzumab alone on day 1 and milatuzumab alone on day 2 to prevent overlapping infusion reactions. Starting week 2, veltuzumab will be given on day 1 and milatuzumab will be given on day 4.
Phase II
EXPERIMENTALPatients will receive veltuzumab IV weekly for 4 doses and milatuzumab IV weekly on day 2 of week 1 and on day 4 of weeks 2-4 for 4 total doses during induction therapy. Patients may continue on therapy to receive extended induction therapy provided they do not experience significant toxicity or rapid disease progression during the initial 4 week induction.
Interventions
Patient will receive milatuzumab weekly for 4 total doses during induction therapy. Induction therapy will be defined as the first 4 weeks of study therapy. During week 1 of induction therapy, patients will receive milatuzumab on day 2. Starting in week 2, milatuzumab will be given on day 4. Provided the patient does not experience excessive toxicity or disease progression during induction therapy, the patient may continue treatment with extended induction therapy, consisting of veltuzumab day 1 and milatuzumab day 4 of weeks 12, 20, 28, and 36.
Patient will receive veltuzumab weekly for 4 total doses during induction therapy. Induction therapy will be defined as the first 4 weeks of study therapy. Provided the patient does not experience excessive toxicity or disease progression during induction therapy, the patient may continue treatment with extended induction therapy, consisting of veltuzumab day 1 and milatuzumab day 4 of weeks 12, 20, 28, and 36.
To correlate Fcγ receptor polymorphisms with response to treatment with the combination of veltuzumab and milatuzumab. Whole blood will be collected pre-treatment on day 1.
Quantitative T-, B-, and NK- cell subsets will be assessed using flow cytometry to quantify the percentage and absolute number of cells expressing CD4, CD8, CD56, CD16, CD19, and CD20 pre-treatment on day 1, after induction (week 5, day 1), and prior to the start of therapy on day 1 week 12, day 1 week 36, and then every 4 months for one year.
To assess the pharmacokinetics of veltuzumab in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma. Pharmacokinetics will be assessed with blood samples collected at the following time points: immediately pre- and post-infusion on day 1 of weeks 1, 2, 4, 12 and 36. One additional sample will be collected each of weeks 5 through 10 (sample may be collected any day during each of these weeks).
To monitor for the development of human anti-veltuzumab antibodies and human anti-milatuzumab antibodies (HAHA) in patients receiving treatment with veltuzumab and milatuzumab. Patients will be monitored for the development of HAHA at the following timepoints: pre-treatment on day 1 of week 1, pre-treatment on day 1 of week 4, pre-treatment on day 1 of week 12, and pre-treatment on day 1 of week 36.
Patient will receive veltuzumab and milatuzumab weekly for 4 total doses during induction therapy. Induction therapy will be defined as the first 4 weeks of study therapy. During week 1 of induction therapy, patients will receive veltuzumab on day 1 and milatuzumab on day 2. Starting in week 2, veltuxumab will be given on day 1 and milatuzumab will be given on day 4. Provided the patient does not experience excessive toxicity or disease progression during induction therapy, the patient may continue treatment with extended induction therapy, consisting of veltuzumab day 1 and milatuzumab day 4 of weeks 12, 20, 28, and 36.
Eligibility Criteria
You may qualify if:
- Histologically confirmed B-cell non-Hodgkin lymphoma (NHL), including any of the following:
- Marginal zone lymphoma
- Waldenstrom macroglobulinemia (lymphoplasmacytic lymphoma)
- Follicular lymphoma
- Mantle cell lymphoma
- Relapsed or refractory disease after ≥ 1 prior therapy
- Patients with rituximab-refractory disease (defined as having less than a partial response to the prior rituximab-containing regimen) or rituximab-sensitive disease (defined as having a complete response or partial response to the last rituximab-containing regimen \[provided it has been ≥ 3 months since the last dose of rituximab\]) are eligible.
- Age \>18 years.
- Eastern Cooperative Oncology Group (ECOG)performance status 0-2.
- Patients must have normal organ and marrow function as defined below:
- Absolute neutrophil count ≥ 1000/μL
- Platelets ≥ 75,000/μL
- Total bilirubin ≤ 2.0 X institutional upper limit of normal
- AST(SGOT)/ALT(SGPT) ≤ 2.5 X institutional upper limit of normal
- Creatinine ≤ 2.0 mg/dL
- +6 more criteria
You may not qualify if:
- Must be recovered from all toxicities from prior therapy or radiation (excluding alopecia).
- No known CNS lymphoma.
- History of documented human anti-globulin antibodies.
- No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations.
- HIV-positive patients.
- Pregnant women.
- Patients with secondary malignancies with exception of non-melanomatous skin cancers.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Beth Christianlead
- Gilead Sciencescollaborator
Study Sites (1)
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
Related Publications (1)
Christian BA, Poi M, Jones JA, Porcu P, Maddocks K, Flynn JM, Benson DM Jr, Phelps MA, Wei L, Byrd JC, Wegener WA, Goldenberg DM, Baiocchi RA, Blum KA. The combination of milatuzumab, a humanized anti-CD74 antibody, and veltuzumab, a humanized anti-CD20 antibody, demonstrates activity in patients with relapsed and refractory B-cell non-Hodgkin lymphoma. Br J Haematol. 2015 Jun;169(5):701-10. doi: 10.1111/bjh.13354. Epub 2015 Apr 7.
PMID: 25847298RESULT
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Beth Christian
- Organization
- The Ohio State University Comprehensive Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Beth Christian, MD
Ohio State University
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
October 2, 2009
First Posted
October 5, 2009
Study Start
September 1, 2009
Primary Completion
April 1, 2015
Study Completion
September 1, 2015
Last Updated
February 6, 2017
Results First Posted
February 6, 2017
Record last verified: 2016-12
Data Sharing
- IPD Sharing
- Will not share