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A Phase 1 Study of Lenalidomide Maintenance Following Allogeneic Hematopoietic Cell Transplantation in Patients With Select High Risk Hematological Malignancies


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Adult Acute Myeloid Leukemia in Remission, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(15;17)(q22;q12), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), Adult Grade III Lymphomatoid Granulomatosis, Adult Nasal Type Extranodal NK/T-cell Lymphoma, Anaplastic Large Cell Lymphoma, Angioimmunoblastic T-cell Lymphoma, Cutaneous B-cell Non-Hodgkin Lymphoma, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Hepatosplenic T-cell Lymphoma, Intraocular Lymphoma, Nodal Marginal Zone B-cell Lymphoma, Noncutaneous Extranodal Lymphoma, Peripheral T-cell Lymphoma, Post-transplant Lymphoproliferative Disorder, Prolymphocytic Leukemia, Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Diffuse Mixed Cell Lymphoma, Recurrent Adult Diffuse Small Cleaved Cell Lymphoma, Recurrent Adult Grade III Lymphomatoid Granulomatosis, Recurrent Adult Immunoblastic Large Cell Lymphoma, Recurrent Adult Lymphoblastic Lymphoma, Recurrent Adult T-cell Leukemia/Lymphoma, Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Recurrent Marginal Zone Lymphoma, Recurrent Mycosis Fungoides/Sezary Syndrome, Recurrent Small Lymphocytic Lymphoma, Refractory Chronic Lymphocytic Leukemia, Refractory Hairy Cell Leukemia, Richter Syndrome, Small Intestine Lymphoma, Splenic Marginal Zone Lymphoma, T-cell Large Granular Lymphocyte Leukemia, Testicular Lymphoma, Waldenström Macroglobulinemia

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Trial Information

A Phase 1 Study of Lenalidomide Maintenance Following Allogeneic Hematopoietic Cell Transplantation in Patients With Select High Risk Hematological Malignancies


PRIMARY OBJECTIVES:

I. Determine the maximal-tolerable dose (MTD) of lenalidomide after allogeneic hematopoietic
stem cell transplantation (AHSCT) in patients with advanced acute myeloid leukemia (AML),
non-Hodgkin's lymphoma (NHL), or chronic lymphocytic leukemia (CLL).

II. Define the qualitative and quantitative toxicities of lenalidomide in regard to organ
specificity, time course, predictability, and reversibility following AHSCT in these
patients.

SECONDARY OBJECTIVES:

I. Determine the anti-tumor response in patients treated with lenalidomide after AHSCT when
compared with historical controls.

II. Evaluate the plasma and cellular pharmacokinetics of lenalidomide in patients enrolled
on this study and interactions with supportive agents such as calcineurin inhibitors.

III. Evaluate the frequency of acute and chronic graft-vs-host disease and graft failure in
patients enrolled on this study.

IV. Prospectively assess the feasibility of administering an oral agent post-transplant as
measured by efficiency of patients being registered to therapy early and also meeting
eligibility criteria for lenalidomide treatment.

V. Perform pharmacodynamic studies following lenalidomide treatment including development of
B, T, and myeloid cell chimerism; assessment of immune activation; cytokines; tumor cell
expression of co-stimulatory molecules; development of anti-tumor antibodies and
immunoglobulin recovery; and re-expression of microRNAs that may mediate lenalidomide
anti-tumor effect.

OUTLINE: This is a multicenter, dose-escalation study. Patients are stratified according to
diagnosis (high-risk acute myeloid leukemia vs non-Hodgkin lymphoma vs high-risk chronic
lymphocytic leukemia, small lymphocytic lymphoma, or B-prolymphocytic leukemia).

Patients receive oral lenalidomide once daily on days 1-28. Courses repeat every 28 days for
up to 24 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo blood and bone marrow biopsies and aspirate collection at baseline and
periodically during study for pharmacokinetic and pharmacodynamic studies. Buccal swab
samples are also collected at baseline and analyzed for genetic polymorphisms.

After completion of study therapy, patients are followed up for up to 1 year.


Inclusion Criteria:



- Histologically confirmed hematologic malignancy meeting 1 of the following criteria:

- High-risk acute myeloid leukemia meeting 1 the following criteria:

- First complete response (CR) and ≥ 60 years of age OR < 60 years of age
with high-risk cytogenetics as defined by CALGB OR high-molecular risk and
not eligible or willing to undergo myeloablative conditioning

- Second or later complete remission

- Not in remission but with < 5% blasts within 3 weeks of start of
conditioning chemotherapy for allogeneic transplantation

- Patients with a history of CNS involvement allowed provided disease is in
remission at the time of transplantation

- Patients with non-Hodgkin lymphoma who are candidates for allogeneic stem cell
transplantation will be eligible; patients who have relapsed status post
autologous transplantation are eligible as long as they demonstrate chemotherapy
sensitive disease; patients with a history of CNS involvement are eligible if
this aspect of the disease is in remission at the time of transplantation

- High-risk chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL),
or primary and secondary B-prolymphocytic leukemia (PLL) meeting 1 of the
following criteria:

- del(17p13.1) disease that has been treated (may have been given as
consolidation therapy)

- Less than PR to chemoimmunotherapy or relapsed within 2 years of treatment

- Nucleoside analog refractory disease or disease that relapsed after two
prior regimens

- Patients with Richter (large cell) transformation allowed provided the
large cell component of the disease is in remission (< 10% large cells in
the bone marrow allowed)

- Patient has undergone an allogeneic stem cell transplantation using a
reduced-intensity or non-myeloablative conditioning regimen within the past 60 days

- At least 40% T-cell donor chimerism at day 30

- ECOG performance status 0-2 (Karnofsky 60-100%)

- Life expectancy > 3 months

- Myeloid engraftment with absolute neutrophil count > 1,000/μL and platelet count >
50,000/μL (after allogeneic hematopoietic stem cell transplantation [AHSCT])

- Total bilirubin normal

- AST and ALT ≤ 2.5 times upper limit of normal (ULN)

- AST < 3 times ULN after AHSCT

- Creatinine clearance ≥ 50 mL/min in stratum 1 or ≥ 30 mL/min in stratum 2

- DLCO > 40% with no symptomatic pulmonary disease

- LVEF ≥ 30% by echocardiogram or MUGA

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must agree to use two acceptable methods of contraception (one
highly effective method and one additional effective method) or practice abstinence
for ≥ 28 days before, during, and ≥ 28 days after completing lenalidomide

- HIV negative

- No uncontrolled infection requiring intravenous therapy or poorly controlled diabetes
mellitus

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to lenalidomide

- No uncontrolled intercurrent illness including, but not limited to, any of the
following:

- Ongoing or active infection

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia

- Psychiatric illness and/or social situations that would limit compliance with
study requirements

- No history of grade 3 or 4 graft-vs-host disease (GVHD)

- If patient has acute GVHD grade 1 or 2, GVHD must be controlled and dose of oral
prednisone or equivalent ≤ 20 mg per day (after AHSCT)

- More than 4 weeks since prior chemotherapy (excluding steroids), radiotherapy, or
radioimmunoconjugate therapy (6 weeks for nitrosoureas or mitomycin C) and recovered

- No other concurrent investigational agents

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

MTD of lenalidomide after allogeneic hematopoietic stem cell transplantation graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0

Outcome Time Frame:

Up to day 28

Safety Issue:

Yes

Principal Investigator

Leslie Andritsos

Investigator Role:

Principal Investigator

Investigator Affiliation:

Ohio State University

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2011-02551

NCT ID:

NCT01254578

Start Date:

November 2010

Completion Date:

Related Keywords:

  • Adult Acute Myeloid Leukemia in Remission
  • Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
  • Adult Acute Myeloid Leukemia With Del(5q)
  • Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
  • Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
  • Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
  • Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
  • Adult Grade III Lymphomatoid Granulomatosis
  • Adult Nasal Type Extranodal NK/T-cell Lymphoma
  • Anaplastic Large Cell Lymphoma
  • Angioimmunoblastic T-cell Lymphoma
  • Cutaneous B-cell Non-Hodgkin Lymphoma
  • Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
  • Hepatosplenic T-cell Lymphoma
  • Intraocular Lymphoma
  • Nodal Marginal Zone B-cell Lymphoma
  • Noncutaneous Extranodal Lymphoma
  • Peripheral T-cell Lymphoma
  • Post-transplant Lymphoproliferative Disorder
  • Prolymphocytic Leukemia
  • Recurrent Adult Burkitt Lymphoma
  • Recurrent Adult Diffuse Large Cell Lymphoma
  • Recurrent Adult Diffuse Mixed Cell Lymphoma
  • Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
  • Recurrent Adult Grade III Lymphomatoid Granulomatosis
  • Recurrent Adult Immunoblastic Large Cell Lymphoma
  • Recurrent Adult Lymphoblastic Lymphoma
  • Recurrent Adult T-cell Leukemia/Lymphoma
  • Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
  • Recurrent Grade 1 Follicular Lymphoma
  • Recurrent Grade 2 Follicular Lymphoma
  • Recurrent Grade 3 Follicular Lymphoma
  • Recurrent Mantle Cell Lymphoma
  • Recurrent Marginal Zone Lymphoma
  • Recurrent Mycosis Fungoides/Sezary Syndrome
  • Recurrent Small Lymphocytic Lymphoma
  • Refractory Chronic Lymphocytic Leukemia
  • Refractory Hairy Cell Leukemia
  • Richter Syndrome
  • Small Intestine Lymphoma
  • Splenic Marginal Zone Lymphoma
  • T-cell Large Granular Lymphocyte Leukemia
  • Testicular Lymphoma
  • Waldenström Macroglobulinemia
  • Congenital Abnormalities
  • Burkitt Lymphoma
  • Immunoblastic Lymphadenopathy
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Hairy Cell
  • Leukemia, Lymphoid
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Prolymphocytic
  • Leukemia, T-Cell
  • Leukemia-Lymphoma, Adult T-Cell
  • Lymphoma
  • Lymphoma, Follicular
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin
  • Lymphomatoid Granulomatosis
  • Lymphoproliferative Disorders
  • Waldenstrom Macroglobulinemia
  • Mycoses
  • Mycosis Fungoides
  • Sezary Syndrome
  • Lymphoma, B-Cell
  • Lymphoma, Large-Cell, Immunoblastic
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Lymphoma, T-Cell
  • Lymphoma, T-Cell, Cutaneous
  • Lymphoma, T-Cell, Peripheral
  • Lymphoma, Large-Cell, Anaplastic
  • Lymphoma, B-Cell, Marginal Zone
  • Lymphoma, Extranodal NK-T-Cell
  • Lymphoma, Mantle-Cell
  • Hematologic Neoplasms
  • Leukemia, Large Granular Lymphocytic

Name

Location

Ohio State University Medical CenterColumbus, Ohio  43210