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
- 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
- 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
- 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
- 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
- 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
- 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.
- 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
- 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.