Phase I Study of Milatuzumab for Graft Versus Host Disease

Sponsor

Gilead Sciences (Industry)

Overall Status

Terminated

CT.gov ID

NCT01663766

Collaborator

Ohio State University (Other)

Enrollment

Location

Arm

14.9

Actual Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
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)	Drug: milatuzumab	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

12 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Dec 1, 2013

Actual Primary Completion Date :

Mar 1, 2015

Actual Study Completion Date :

Mar 1, 2015

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Determine the therapeutic efficacy of milatuzumab in this patient population [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.