Phase I Study of Milatuzumab for Graft Versus Host Disease

NCT01663766 | Terminated Phase 1

• 1 other identifier: IM-T-IMMU-115-03
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

GVHD (Acute or Chronic); Acute Myeloid or Lymphoblastic Leukemia (AML or ALL); Myelodysplastic Syndrome; Chronic Myelogenous Leukemia (CML); Multiple Myeloma (MM); Non-Hodgekin Lymphoma (NHL-both Follicular & Diffuse Large Cell); Chronic Lymphocytic Leukemia or Small Lymphocytic Leukemia (CLL or SLL)

Keywords

GVHD (acute or chronic); acute myeloid or lymphoblastic leukemia (AML or ALL); myelodysplastic syndrome; Chronic myelogenous leukemia (CML); Multiple Myeloma (MM); Non-Hodgekin lymphoma (NHL-both follicular & diffuse large cell); Chronic lymphocytic leukemia or small lymphocytic leukemia (CLL or SLL)

Outcome Measures

Primary Outcomes (1)

• All patients administered any dose of study drug will be included in the evaluation of safety

  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 Outcomes (1)

• Determine the therapeutic efficacy of milatuzumab in this patient population

  Efficacy will be assessed 30 days after treatment.

Study Arms (1)

Milatuzumab

EXPERIMENTAL

Milatuzumab will be added to the standard GVHD reduced intensity consitioning and prophylaxis regimen of fludarabine, busulfan, tacrolimus and low-dose methotrexate.

Drug: milatuzumab

Interventions

milatuzumab DRUG

Milatuzumab is a humanized anti-CD74 antibody that is administered intravenously.

Also known as: IMMU-115, hLL1, anti-CD74

Milatuzumab

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gilead Sciences: lead
• Ohio State University: collaborator

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Graft vs Host Disease; Bronchiolitis Obliterans Syndrome; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Multiple Myeloma; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

milatuzumab

Condition Hierarchy (Ancestors)

Immune System Diseases; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, Myeloid; Bone Marrow Diseases; Myeloproliferative Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Leukemia, B-Cell

Study Officials

• William Wegener, MD, PhD

  Gilead Sciences

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2012
• First Posted: August 13, 2012
• Study Start: December 1, 2013
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: August 19, 2021

Record last verified: 2020-09

Locations

US (1)