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LymphomaPhase 1/2NCT00989586

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

A Phase 1/2 study testing milatuzumab, veltuzumab and Correlative/Special Studies in people with Lymphoma, run by Beth Christian at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lymphoma
What is being tested?
milatuzumab, veltuzumab and Correlative/Special Studies
Could I receive a placebo?
No, everyone receives an active treatment
How many people
35 participants
Where
1 siteUnited States
Study dates
Sep 2009to Sep 2015
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 21Show fewer
  • 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.

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

Other trials in United States

About this study

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

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.

Read the 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.

Conditions
Lymphoma
Being tested
milatuzumab, veltuzumab, Correlative/Special Studies, Quantitative T-, B-, and NK cell subsets, Pharmacokinetics
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
Medical subject headings
Lymphoma, Lymphoma, Mantle-Cell, Lymphoma, Follicular, Lymphoma, B-Cell, Marginal Zone, Waldenstrom Macroglobulinemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • milatuzumabBiological

    Also called monoclonal antibody

    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.

  • veltuzumabBiological

    Also called monoclonal antibody

    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.

  • Correlative/Special StudiesProcedure or surgery

    Also called blood samples

    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 subsetsProcedure or surgery

    Also called blood samples

    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.

  • PharmacokineticsProcedure or surgery

    Also called blood samples

    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).

  • PharmacokineticsProcedure or surgery

    Also called blood samples

    To assess the pharmacokinetics of milatuzumab 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 2 of week 1 and day 1 of weeks 2, 4, 12 and 36. Additional samples will be collected days 3 through 6 of week 1.

  • Human Anti-Human AntibodiesProcedure or surgery

    Also called blood samples

    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.

  • veltuzumab and milatuzumabBiological

    Also called monoclonal antibody

    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.

Study groups in NCT00989586
Study groupRoleWhat they receive
Phase IExperimentalPhase 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.
Receives: Biological: milatuzumab; Biological: veltuzumab; Procedure: Correlative/Special Studies; Procedure: Quantitative T-, B-, and NK cell subsets; Procedure: Pharmacokinetics; Procedure: Human Anti-Human Antibodies
Phase IIExperimentalPatients 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.
Receives: Biological: veltuzumab and milatuzumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose Limiting Toxicity (DLT) for Phase I Patients

    Dose-limiting toxicity was assessed during induction therapy for phase I.

    Measured: up to 2 years

  2. Maximum Tolerated Dose (MTD)for Phase I Patients

    Patients received a fixed dose of Veltuzumab IV 200 mg/m2 and Milatuzumab was dose escalated

    Measured: up to 2 years

  3. 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.

    Measured: Up to 2 years

Secondary outcomes (6)

  1. Progression-free Survival (PFS)

    Progression is defined using International Response Criteria (Cheson JCO 2007), as a >= 50% increase from nadir in the SPD of any previously involved nodes, or in a single involved node, or at least a 50% increase in the longest diameter of any single previously identified node more than 1 cm in its short axis, or the size of other lesions (eg, splenic or hepatic nodules), or the appearance of new lesions.

    Measured: up to 2 years

  2. Fcγ-receptor Polymorphism Response to Treatment

    The relationship between overall response rate (ORR) and Fcy receptor status. A two-sided chi-square test or exact test with α = 0.05 will be used to test the homogeneity of the ORR among the three genotypes.

    Measured: up to 2 years

  3. Quantitative T-, B-, and NK-cell Subsets Using Flow Cytometry

    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 at screening, after induction, and prior to the start of therapy on day 1 week 12, day 1 week 28, and then every 4 months for one year.

    Measured: up to 1 year

  4. Access Pharmacokinetics Through AUC0-∞ (Area Under Curve)

    Evaluation of pharmacokinetics (Pk) of veltuzumab and milatuzumab was performed for patients included in the trial. Statistically, descriptive data of PK parameters will be computed. Relationships between such parameters as dose and AUC, volume of distribution, clearance, and others will be evaluated, but be preliminary due to the small sample size.

    Measured: 0, 24, 48, 72, 96 and 120 hours post-does

  5. Access Pharmacokinetics Through Cmax

    Evaluation of pharmacokinetics of veltuzumab and milatuzumab was performed for patients included in the trial. Statistically, descriptive data of PK parameters will be computed. Relationships between such parameters as dose and AUC, volume of distribution, clearance, and others will be evaluated, but be preliminary due to the small sample size.

    Measured: 0, 24, 48, 72, 96 and 120 hours post-dose

  6. Monitor Human Anti-veltuzumab Antibodies and Human Anti-milatuzumab (HAHA)

    Patients will be monitored for the development of human anti-veltuzumab antibodies and human anti-milatuzumab antibodies (HAHA).

    Measured: up to 36 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Oct 2009 (estimated)
  2. Study startSep 2009
  3. Primary completionApr 2015
  4. Study completionSep 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
35 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00989586
Sponsor's protocol ID
OSU-09024
Other IDs
NCI-2011-03150
Status last verified
Dec 2016
First submitted
2 Oct 2009
Last updated
6 Feb 2017
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • 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.

    PubMed 25847298

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing milatuzumab, veltuzumab and Correlative/Special Studies in people with Lymphoma, run by Beth Christian at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Feb 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose Limiting Toxicity (DLT) for Phase I Patients (time frame: up to 2 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00989586, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2017.

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