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HLA-mismatched Allogeneic Cellular Therapy (HMMACT) After Chemotherapy in High Risk Acute Myeloid Leukemia


Phase 1
N/A
N/A
Open (Enrolling)
Both
Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Monoblastic Leukemia (M5a), Adult Acute Monocytic Leukemia (M5b), Adult Acute Myeloblastic Leukemia With Maturation (M2), Adult Acute Myeloblastic Leukemia Without Maturation (M1), 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(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), Adult Acute Myelomonocytic Leukemia (M4), Adult Erythroleukemia (M6a), Adult Pure Erythroid Leukemia (M6b), Childhood Acute Erythroleukemia (M6), Childhood Acute Megakaryocytic Leukemia (M7), Childhood Acute Monoblastic Leukemia (M5a), Childhood Acute Monocytic Leukemia (M5b), Childhood Acute Myeloblastic Leukemia With Maturation (M2), Childhood Acute Myeloblastic Leukemia Without Maturation (M1), Childhood Acute Myeloid Leukemia in Remission, Childhood Acute Myelomonocytic Leukemia (M4), Recurrent Adult Acute Myeloid Leukemia, Recurrent Childhood Acute Myeloid Leukemia, Secondary Acute Myeloid Leukemia, Untreated Adult Acute Myeloid Leukemia, Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

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Trial Information

HLA-mismatched Allogeneic Cellular Therapy (HMMACT) After Chemotherapy in High Risk Acute Myeloid Leukemia


PRIMARY OBJECTIVES:

I. To assess the feasibility of cytarabine based chemotherapy and human leukocyte antigen
(HLA)-mismatched allogeneic cellular therapy (HMMACT) in patients with high risk acute
myeloid leukemia (AML), with feasibility measured by induction mortality (IM) and complete
response rate.

SECONDARY OBJECTIVES:

I. To obtain preliminary estimates of clinical outcome following cytarabine based
chemotherapy and HMMACT in patients with high risk AML, as measured by event free survival
(EFS) and overall survival (OS).

II. To further evaluate the safety outcomes of induction and consolidation of cytarabine and
HMMACT in terms of serious infections (grade 4), time to recovery of absolute neutrophil
counts and platelets and incidence of graft versus host disease (GvHD).

III. To further evaluate the feasibility of this approach in terms of identifying a suitable
donor in this elderly population.

IV. To compare in preliminary manner the clinical outcomes of cytarabine and HMMACT in
patients with high risk AML as measured by complete response rate (CRR), event free survival
(EFS) and overall survival (OS) by donor/recipient HLA-C1 vs C2 pairs.

V. To characterize in a preliminary manner, the numbers of suppressor regulatory T cells
(Tregs), T helper 17 cells (Th17), and cytotoxic T cells during pre and post HMMACT
treatment, and with clinical outcomes in leukemia.

OUTLINE:

INDUCTION CHEMOTHERAPY: Patients receive mitoxantrone hydrochloride intravenously (IV) on
days 1-3 and cytarabine IV on days 1-7.

HMMACT: Patients receive filgrastim (G-CSF) mobilized peripheral blood stem cells (G-PBSC)
on day 9. After completion of study treatment, patients are followed up monthly for 3
years.


Inclusion Criteria:



- Patients must have a histologically and cytological confirmed acute myeloid leukemia,
high risk AML defined as:

- Age > 60, or

- Presence of complex cytogenetic abnormalities (with > 3 cytogenetic
abnormalities), del (7q, -5, -7), t(9,22), q(34,11.2), or

- Secondary AML, or

- A white blood cell count of > 50 x10^9/L

- Patients must be medical ineligible for allogeneic stem cell transplant (alloSCTx) or
not have a known fully HLA matched sibling

- Patients must have measurable or evaluable disease

- Diagnosis of AML according to World Health Organization (WHO) diagnostic criteria (at
least 20% blasts in the peripheral blood or bone marrow), with
French-American-British Cooperative group (FAB) classification other than M3 (acute
promyelocytic leukemia), documented by bone marrow aspiration and biopsy performed
within 14 days prior to administration of 1st dose of remission induction
chemotherapy; if a bone marrow aspirate and biopsy were obtained within 28 days prior
to the first dose of remission induction therapy then these tests may be submitted
for review at University of Southern California (USC) and a repeat screening bone
marrow does not need to be conducted

- Patient has at least one medically fit first degree family member expected to be HLA
mismatched at 4-6/10 loci (parent, full sibling, child)

- Absolute neutrophil count (ANC) > 1500, unless due to direct bone marrow involvement
of disease

- Platelets > 75,000, unless due to direct bone marrow involvement of disease

- Hemoglobin > 8.0 gm/dL, transfusion allowed

- Serum creatinine < 2.0 x the upper limits of institutional normal (ULN)

- Total bilirubin < 1.5 x the upper limits of institutional normal

- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT )< 2.5 x the upper
limits of institutional normal (=< 5 x ULN for patients with liver involvement of
leukemia)

- Diffusing capacity of the lung for carbon monoxide (DLCO)/alveolar volume (VA) > 50%

- Cardiac left ventricular ejection fraction (LVEF) > 45%

- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

- Estimated survival of at least 3 months

- Patients must be able to understand and agree to sign an Institutional Review Board
(IRB)-approved informed consent form

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control) prior to study entry, for the duration
of study, and for two months after study participation

- DONOR: Donor screening; all donors will meet the standard blood donor criteria
established by the participating local blood center, American Association of Blood
Banks (AABB)

- DONOR: Donors will be selected from among the subject's relatives, adult children
preferred

- DONOR: Infectious disease testing will be done per Hemacare policy and AAAB
guidelines

- DONOR: Donor and intended recipient red cell type and compatibility will be
determined

- DONOR: Donors will be pre-selected on the basis of HLA haploidentity

- DONOR: If patient is cytomegalovirus (CMV)-negative, donors who are CMV-negative will
be preferred; CMV serology of the donor will be tested prior to the allogeneic cell
donation; donations from CMV-positive donors to CMV-negative recipients will be given
if no CMV negative donor is available, and CMV surveillance and pre-emptive treatment
given

Exclusion Criteria:

- Patients who have received prior therapy, i.e. chemotherapy, other than demethylating
agents such as azacytidine or decitabine

- Patients who have uncontrolled systemic infections, coagulation disorders, or other
major medical illnesses of the cardiovascular or respiratory systems

- Patients who are pregnant and/or lactating

- Patients who have had non-biopsy surgery in the last 10 days

- Patients who have active central nervous system (CNS) disease; patients with
previously treated leptomeningeal disease without evidence of remaining leukemia
cells by spinal fluid will be eligible

- Patients with known active autoimmune disorder

- Patients known to be human immunodeficiency virus (HIV)-positive or have active
hepatitis B or C

- Patients concurrently taking the following drugs are excluded: mycophenolate,
cyclosporine, prednisone > 20mg/day, or immunosuppressive agents

- DONOR: Personal or family history of severe sickle cell disease or variant (unless
donor has tested negative); testing for the presence of hemoglobin S is not required

- DONOR: Positive infectious disease test as dictated by blood collection center's
standard operating procedure (SOP)

- DONOR: Current uncontrolled hypertension

- DONOR: Diabetes mellitus

- DONOR: Active peptic ulcer disease

- DONOR: Pregnant or breast-feeding

- DONOR: Currently taking lithium therapy

- DONOR: History of autoimmune disease

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Induction mortality

Outcome Time Frame:

Up to 8 weeks

Safety Issue:

No

Principal Investigator

Ann Mohrbacher

Investigator Role:

Principal Investigator

Investigator Affiliation:

USC/Norris Comprehensive Cancer Center

Authority:

United States: Institutional Review Board

Study ID:

9L-11-8

NCT ID:

NCT01801046

Start Date:

March 2013

Completion Date:

April 2017

Related Keywords:

  • Adult Acute Megakaryoblastic Leukemia (M7)
  • Adult Acute Monoblastic Leukemia (M5a)
  • Adult Acute Monocytic Leukemia (M5b)
  • Adult Acute Myeloblastic Leukemia With Maturation (M2)
  • Adult Acute Myeloblastic Leukemia Without Maturation (M1)
  • 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(16;16)(p13;q22)
  • Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
  • Adult Acute Myelomonocytic Leukemia (M4)
  • Adult Erythroleukemia (M6a)
  • Adult Pure Erythroid Leukemia (M6b)
  • Childhood Acute Erythroleukemia (M6)
  • Childhood Acute Megakaryocytic Leukemia (M7)
  • Childhood Acute Monoblastic Leukemia (M5a)
  • Childhood Acute Monocytic Leukemia (M5b)
  • Childhood Acute Myeloblastic Leukemia With Maturation (M2)
  • Childhood Acute Myeloblastic Leukemia Without Maturation (M1)
  • Childhood Acute Myeloid Leukemia in Remission
  • Childhood Acute Myelomonocytic Leukemia (M4)
  • Recurrent Adult Acute Myeloid Leukemia
  • Recurrent Childhood Acute Myeloid Leukemia
  • Secondary Acute Myeloid Leukemia
  • Untreated Adult Acute Myeloid Leukemia
  • Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies
  • Congenital Abnormalities
  • Neoplasms
  • Leukemia
  • Leukemia, Erythroblastic, Acute
  • Leukemia, Megakaryoblastic, Acute
  • Leukemia, Monocytic, Acute
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myelomonocytic, Acute
  • Leukemia, Myelomonocytic, Chronic

Name

Location

USC Norris Comprehensive Cancer CenterLos Angeles, California  90089