Phase I Study of Milatuzumab for Graft Versus Host Disease

August 12, 2021 updated by: Gilead Sciences

A Phase I Study of Milatuzumab (hLL1) for Prevention of Acute Graft Versus Host Disease Following Reduced-Intensity Conditioning Allogeneic Stem Cell Transplant in Patients With Hematologic Malignancies

This study will assess the safety and tolerability of milatuzumab (IMMU-115) when added to a standard regimen to prevent Graft vs. Host Disease (GVHD) in patients with hematologic malignancies undergoing stem cell transplant.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Ohio State University Comprehensive Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Males or non-pregnant, non-lactating females, ≥ 18 years of age
  • Able to understand and willing to sign informed consent.
  • Histologically confirmed hematologic malignancy that is deemed best treated by RIC allogeneic SCT, including:
  • Acute myeloid or lymphoblastic leukemia (AML, ALL) with < 5% blasts in the bone marrow
  • Myelodysplastic syndrome and intermediate-2 or high-risk IPSS score with < 5% blasts in the bone marrow
  • Chronic myelogenous leukemia failing to respond to at least two different tyrosine kinase inhibitors
  • Multiple myeloma that has relapsed following autologous stem cell transplant
  • Follicular lymphoma (grades 1, 2, or 3a by WHO criteria) or monocytoid lymphoma that has relapsed following at least two prior chemotherapy regimens and with either no lymph node groups ≥ 3 cm or with a ≥ 50% reduction in estimated lymph node diameter with most recent salvage therapy
  • Diffuse large B-cell NHL that has relapsed after at least 2 prior chemotherapy regimens (could include high-dose chemotherapy with autologous stem cell rescue) and is still sensitive to chemotherapy by virtue of a PR or CR following most recent salvage chemotherapy
  • Transformed follicular lymphoma that has achieved a PR or CR following chemotherapy
  • Mantle cell lymphoma that has relapsed after at least 2 prior chemotherapy regimens (could include high-dose chemotherapy with autologous stem cell rescue)
  • CLL/SLL/PLL that meets one of the following:
  • del (17p13.1) in first remission
  • Response no better than a PR with chemoimmunotherapy or relapse within 2 years of chemoimmunotherapy
  • Richter's transformation
  • Complex karyotype
  • At least 4 weeks beyond prior chemotherapy (excluding steroids), antibody therapy, radiation, or radioimmunoconjugate therapy, and with any kinase inhibitors discontinued at least one week prior to starting the conditioning regimen.
  • ECOG performance status ≤ 2
  • Life expectancy of greater than 3 months
  • Adequate organ function measured by the following within seven days of beginning conditioning:
  • AST (SGOT) ≤ 3.0 x institutional upper limit of normal (IULN)
  • Total bilirubin ≤ 1.5 xIULN unless due to Gilbert's disease
  • Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 50 mL/min
  • DLCO > 40% with no symptomatic pulmonary disease
  • LVEF by echocardiogram or MUGA of at least 30%
  • Women of child bearing potential and men must agree to use contraception prior to study entry and for the duration of study participation.
  • Matched (8/8) related or matched unrelated donor identified. Haploidentical or umbilical cord grafts are not allowed.
  • Donor willing to donate peripheral blood stem cells and meets institutional criteria for stem cell donation.

Exclusion Criteria:

  • Prior allogeneic stem cell transplant
  • Patients requiring a myeloablative conditioning regimen
  • Patients best served by a bone marrow transplant are not eligible as this study will be restricted only to peripheral stem cells.
  • No suitable donor identified
  • Prior anaphylactic response or Grade 4 infusion reaction to milatuzumab
  • 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 that would limit compliance with study requirements.
  • Patients with active hepatitis B infection are not eligible. Patients with a history of hepatitis B (surface antigen or core antibody positive) must take lamivudine or equivalent during study therapy and for one year after completion of milatuzumab.
  • LVEF < 30%
  • Seropositivity for HIV or Hepatitis C
  • Patients with known CNS lymphoma are excluded because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
  • Active secondary malignancies with the exception of non-melanomatous skin cancers or low risk prostate cancer under observation.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Milatuzumab
Milatuzumab will be added to the standard GVHD reduced intensity consitioning and prophylaxis regimen of fludarabine, busulfan, tacrolimus and low-dose methotrexate.
Drug: milatuzumab
Milatuzumab is a humanized anti-CD74 antibody that is administered intravenously.
Other Names:
  • IMMU-115
  • hLL1
  • anti-CD74

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
All patients administered any dose of study drug will be included in the evaluation of safety
Time Frame: Safety will be assessed by measuring the change from baseline during 7 days of treatment and up to 30 days after treatment
Safety will be measured by physical examinations and hematology and chemistry blood tests. Cardiac safety will be done using MUGA scans or echocardiograms. These assessments will be done routinely during treatment and up to 30 days after treatment and any change from baseline will be assessed. Long term safety will be assessed every 3 months after that for up to 1 year; any change from baseline will be assessed.
Safety will be assessed by measuring the change from baseline during 7 days of treatment and up to 30 days after treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determine the therapeutic efficacy of milatuzumab in this patient population
Time Frame: Efficacy will be assessed 30 days after treatment.
Acute GVHD will be assessed at days +30 and +100 by laboratory testing. Chronic GVHD assessment will be performed at days +100, +270 & +365 after stem cell transplant.
Efficacy will be assessed 30 days after treatment.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gilead Sciences

Collaborators

Ohio State University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

December 1, 2013

Primary Completion (ACTUAL)

March 1, 2015

Study Completion (ACTUAL)

March 1, 2015

Study Registration Dates

First Submitted

August 7, 2012

First Submitted That Met QC Criteria

August 9, 2012

First Posted (ESTIMATE)

August 13, 2012

Study Record Updates

Last Update Posted (ACTUAL)

August 19, 2021

Last Update Submitted That Met QC Criteria

August 12, 2021

Last Verified

September 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IM-T-IMMU-115-03

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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