Veltuzumab and Milatuzumab in Treating Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

NCT00989586 | Completed Phase 1 Results DMC

• 2 other identifiers: OSU-09024NCI-2011-03150
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 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.

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

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

Study Arms (2)

Phase I

EXPERIMENTAL

Phase 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.

Biological: milatuzumab; Biological: veltuzumab; Procedure: Correlative/Special Studies; Procedure: Quantitative T-, B-, and NK cell subsets; Procedure: Pharmacokinetics; Procedure: Human Anti-Human Antibodies

Phase II

EXPERIMENTAL

Patients 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.

Biological: veltuzumab and milatuzumab

Interventions

milatuzumab BIOLOGICAL

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.

Also known as: monoclonal antibody

Phase I

veltuzumab BIOLOGICAL

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.

Also known as: monoclonal antibody

Phase I

Correlative/Special Studies PROCEDURE

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.

Also known as: blood samples

Phase I

Quantitative T-, B-, and NK cell subsets PROCEDURE

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.

Also known as: blood samples

Phase I

Pharmacokinetics PROCEDURE

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).

Also known as: blood samples

Phase I

Human Anti-Human Antibodies PROCEDURE

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.

Also known as: blood samples

Phase I

veltuzumab and milatuzumab BIOLOGICAL

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.

Also known as: monoclonal antibody

Phase II

Eligibility Criteria

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

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

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.

Sponsors & Collaborators

• Beth Christian: lead
• Gilead Sciences: collaborator

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

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: 25847298 RESULT

Related Links

• Jamesline

MeSH Terms

Conditions

Lymphoma; Lymphoma, Mantle-Cell; Lymphoma, Follicular; Lymphoma, B-Cell, Marginal Zone; Waldenstrom Macroglobulinemia

Interventions

milatuzumab; Antibodies, Monoclonal; veltuzumab; Blood Specimen Collection; Pharmacokinetics

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Metabolism; Pharmacological and Toxicological Phenomena; Physiological Phenomena

Results Point of Contact

• Title: Beth Christian
• Organization: The Ohio State University Comprehensive Cancer Center

beth.christian@osumc.edu

614-293-8858

Study Officials

• Beth Christian, MD

  Ohio State University

  PRINCIPAL INVESTIGATOR

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

Locations

US (1)