Clinical trial NCT00989586: Veltuzumab and Milatuzumab in Treating Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Lymphoma
Keywords: recurrent mantle cell lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
MALT lymphoma
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
recurrent marginal zone lymphoma
Waldenstrom macroglobulinemia
Lead sponsor: Ohio State University Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: Gilead Sciences
First posted: 2009-10-05
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: A phase I/II study of veltuzumab combined with milatuzumab in relapsed and refractory non-Hodgkin's lymphoma. Both agents are well-tolerated in early phase clinical testing with infusion reactions as the primary observed toxicity. Preclinical testing in vitro and in vivo have demonstrated single agent activity for both veltuzumab and milatuzumab. In mantle cell lymphoma cell lines and SCID mouse models, synergist effects were observed when milatuzumab was combined with rituximab. Veltuzumab has several advantages over rituximab including slower off-rates, shorter infusion times, higher potency, and improved therapeutic responses in animal models. Previous and ongoing clinical investigations support the concept of combining monoclonal antibodies in NHL.

Eligibility criteria: Inclusion Criteria:

* 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
* Patients who have relapsed after stem cell transplant are eligible for this trial.
* Patients with active Hepatitis B infection are not eligible.
* Non-pregnant and non-nursing. Women of child bearing potential and men must agree to use contraception prior to study entry and for duration of study participation.
* Must possess the ability to understand and the willingness to sign a written informed consent document.

Phase II

-Must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension \>10 mm or in the case of Waldenstrom's macroglobulinemia, the presence of an IgM paraprotein level 2x the upper limit of normal.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Dose Limiting Toxicity (DLT) for Phase I Patients
timeFrame: up to 2 years
measure: Maximum Tolerated Dose (MTD)for Phase I Patients
timeFrame: up to 2 years
measure: Overall Objective Response Rate
timeFrame: Up to 2 years
Secondary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: up to 2 years
measure: Fcγ-receptor Polymorphism Response to Treatment
timeFrame: up to 2 years
measure: Quantitative T-, B-, and NK-cell Subsets Using Flow Cytometry
timeFrame: up to 1 year
measure: Access Pharmacokinetics Through AUC0-∞ (Area Under Curve)
timeFrame: 0, 24, 48, 72, 96 and 120 hours post-does
measure: Access Pharmacokinetics Through Cmax
timeFrame: 0, 24, 48, 72, 96 and 120 hours post-dose
measure: Monitor Human Anti-veltuzumab Antibodies and Human Anti-milatuzumab (HAHA)
timeFrame: up to 36 weeks
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Ohio State University
name: Beth Christian, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.