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A Phase I/IB Study of Ipilimumab in Patients With Relapsed Hematologic Malignancies After Allogeneic Hematopoietic Cell Transplantation


Phase 1
18 Years
N/A
Open (Enrolling)
Both
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, Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative, Chronic Myelomonocytic Leukemia, Cutaneous B-cell Non-Hodgkin Lymphoma, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Hepatosplenic T-cell Lymphoma, Intraocular Lymphoma, Juvenile Myelomonocytic Leukemia, Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable, Nodal Marginal Zone B-cell Lymphoma, Noncutaneous Extranodal Lymphoma, Peripheral T-cell Lymphoma, Post-transplant Lymphoproliferative Disorder, Previously Treated Myelodysplastic Syndromes, Progressive Hairy Cell Leukemia, Initial Treatment, Recurrent Adult Acute Lymphoblastic Leukemia, Recurrent Adult Acute Myeloid 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 Hodgkin Lymphoma, 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, Refractory Multiple Myeloma, Relapsing Chronic Myelogenous Leukemia, Small Intestine Lymphoma, Splenic Marginal Zone Lymphoma, T-cell Large Granular Lymphocyte Leukemia, Testicular Lymphoma, Waldenstr├Âm Macroglobulinemia

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Trial Information

A Phase I/IB Study of Ipilimumab in Patients With Relapsed Hematologic Malignancies After Allogeneic Hematopoietic Cell Transplantation


PRIMARY OBJECTIVES:

I. To determine the maximum-tolerated dose (MTD) of ipilimumab administered to patients with
relapsed hematologic malignancies following allogeneic stem cell transplantation. (Phase I)
II. To characterize the toxicity of ipilimumab administered at the MTD in this patient
population. (Phase Ib)

SECONDARY OBJECTIVES:

I. To assess response rate by simple descriptive summary statistics. II. To assess
progression free and overall survival by the Kaplan-Meier method.

TERTIARY OBJECTIVES:

I. To assess the phenotypic and functional effects of ipilimumab on immune cells.

II. To assess tumor glucose metabolism using whole-body fludeoxyglucose F 18-positron
emission tomography (FDG-PET) with optional dual time-point imaging.

OUTLINE: This is a dose-escalation study.

INDUCTION PHASE: Patients receive ipilimumab intravenously (IV) over 90 minutes on day
1.Treatment repeats every 21 days for 4 courses in the absence of disease progression or
unacceptable toxicity.

MAINTENANCE PHASE: Patients receive ipilimumab IV over 90 minutes every 12 weeks beginning
at week 24 and then at weeks 36, 48, and 60 in the absence of disease progression or
unacceptable toxicity.

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


Inclusion Criteria:



- Histologically or cytologically confirmed hematologic malignancy

- The following malignancies will be considered eligible if progressive or persistent:

- Chronic Lymphocytic Leukemia (CLL)

- Non-Hodgkin Lymphoma (NHL)

- Hodgkin Lymphoma (HL)

- Multiple Myeloma (MM)

- Acute Leukemia (AML, ALL)

- Myelodysplastic Syndrome (MDS)

- Myeloproliferative Neoplasms (MPN)

- Chronic Myeloid Leukemia (CML)

- Must have undergone allogeneic hematopoietic stem cell transplantation (HSCT)
(regardless of stem cell source)

- Must be less than 3 years after withdrawal of all prophylactic immunosuppression

- Must have baseline donor T cell chimerism of >= 20%

- Life expectancy of greater than 3 months

- Eastern Cooperative Oncology Group (ECOG) performance status =< 2

- Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (unless due to
Gilbert's disease or disease- related hemolysis, then =< 3.0 x ULN)

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 3.0 x institutional ULN

- Creatinine =< 1.5 x institutional ULN

- Must be off all immunosuppressive medications for at least 4 weeks prior to study
entry

- Ability to understand and the willingness to sign a written informed consent document

- Men and women of all races and ethnic groups are eligible for this trial

Exclusion Criteria:

- Participants who have had anti-tumor therapy or other investigational agents within 4
weeks prior to registration (6 weeks for nitrosoureas or mitomycin C), or those who
have not recovered from adverse events due to agents administered more than 4 weeks
prior to registration

- Patients with prior history of severe (grade 3 or 4) acute graft-versus-host disease
(GVHD)

- Patients with a history of prior treatment with ipilimumab, anti-programmed cell
death protein 1 (PD 1) antibody, or cluster of differentiation (CD) 137 agonist
therapy

- Patients who have had donor lymphocyte infusion (DLI) within 8 weeks prior to
registration

- AUTOIMMUNE DISEASE: Patients with a history of inflammatory bowel disease, including
ulcerative colitis and Crohn's disease, are excluded from this study, as are patients
with a history of symptomatic disease (eg, rheumatoid arthritis, systemic progressive
sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [eg,
Wegener's granulomatosis]) and motor neuropathy considered of autoimmune origin (e.g.
Guillain-Barre syndrome and myasthenia gravis); patients with Hashimoto's thyroiditis
are eligible to go on study

- Patients with known chronic human immunodeficiency virus (HIV), hepatitis B or
hepatitis C infections should be excluded because of potential effects on immune
function and/or drug interactions

- 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

- Pregnant women are excluded from this study because ipilimumab is an immunomodulatory
agent with the potential for teratogenic or abortifacient effects

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and
for the duration of study participation; should a woman become pregnant or suspect
she is pregnant while participating in this study, she should inform her treating
physician immediately; men treated or enrolled on this protocol must also agree to
use adequate contraception prior to the study, for the duration of study
participation, and 4 months after completion of ipilimumab administration

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 ipilimumab according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I)

Outcome Time Frame:

At 12 weeks

Safety Issue:

Yes

Principal Investigator

Matthew Davids

Investigator Role:

Principal Investigator

Investigator Affiliation:

Dana-Farber Cancer Institute

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2013-00739

NCT ID:

NCT01822509

Start Date:

April 2013

Completion Date:

Related Keywords:

  • 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
  • Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative
  • Chronic Myelomonocytic Leukemia
  • Cutaneous B-cell Non-Hodgkin Lymphoma
  • Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
  • Hepatosplenic T-cell Lymphoma
  • Intraocular Lymphoma
  • Juvenile Myelomonocytic Leukemia
  • Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable
  • Nodal Marginal Zone B-cell Lymphoma
  • Noncutaneous Extranodal Lymphoma
  • Peripheral T-cell Lymphoma
  • Post-transplant Lymphoproliferative Disorder
  • Previously Treated Myelodysplastic Syndromes
  • Progressive Hairy Cell Leukemia, Initial Treatment
  • Recurrent Adult Acute Lymphoblastic Leukemia
  • Recurrent Adult Acute Myeloid 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 Hodgkin Lymphoma
  • 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
  • Refractory Multiple Myeloma
  • Relapsing Chronic Myelogenous Leukemia
  • Small Intestine Lymphoma
  • Splenic Marginal Zone Lymphoma
  • T-cell Large Granular Lymphocyte Leukemia
  • Testicular Lymphoma
  • Waldenstr├Âm Macroglobulinemia
  • Congenital Abnormalities
  • Burkitt Lymphoma
  • Neoplasms
  • Hodgkin Disease
  • Immunoblastic Lymphadenopathy
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Hairy Cell
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Leukemia, Myelomonocytic, Chronic
  • 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
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Mycoses
  • Mycosis Fungoides
  • Myelodysplastic Syndromes
  • Preleukemia
  • Leukemia, Myelomonocytic, Acute
  • Myeloproliferative Disorders
  • Sezary Syndrome
  • Lymphoma, B-Cell
  • Lymphoma, Large-Cell, Immunoblastic
  • 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
  • Leukemia, Myelomonocytic, Juvenile
  • Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
  • Hematologic Neoplasms
  • Myelodysplastic-Myeloproliferative Diseases
  • Leukemia, Large Granular Lymphocytic

Name

Location

Dana-Farber Cancer InstituteBoston, Massachusetts  02115