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A Two Step Approach to Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation for High Risk Hematologic Malignancies


Phase 2
18 Years
N/A
Not Enrolling
Both
Accelerated Phase Chronic Myelogenous Leukemia, Adult Acute Lymphoblastic Leukemia in Remission, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), Adult Nasal Type Extranodal NK/T-cell Lymphoma, Anaplastic Large Cell Lymphoma, Angioimmunoblastic T-cell Lymphoma, Blastic Phase Chronic Myelogenous Leukemia, Childhood Acute Lymphoblastic Leukemia in Remission, Childhood Burkitt Lymphoma, Childhood Chronic Myelogenous Leukemia, Childhood Diffuse Large Cell Lymphoma, Childhood Immunoblastic Large Cell Lymphoma, Childhood Myelodysplastic Syndromes, Childhood Nasal Type Extranodal NK/T-cell Lymphoma, Chronic Myelomonocytic Leukemia, Chronic Phase Chronic Myelogenous Leukemia, Cutaneous B-cell Non-Hodgkin Lymphoma, de Novo Myelodysplastic Syndromes, Essential Thrombocythemia, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Hepatosplenic T-cell Lymphoma, Intraocular Lymphoma, Juvenile Myelomonocytic Leukemia, Nodal Marginal Zone B-cell Lymphoma, Noncutaneous Extranodal Lymphoma, Peripheral T-cell Lymphoma, Polycythemia Vera, Post-transplant Lymphoproliferative Disorder, Previously Treated Myelodysplastic Syndromes, Primary Myelofibrosis, 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 Childhood Acute Myeloid Leukemia, Recurrent Childhood Anaplastic Large Cell Lymphoma, Recurrent Childhood Grade III Lymphomatoid Granulomatosis, Recurrent Childhood Large Cell Lymphoma, Recurrent Childhood Lymphoblastic Lymphoma, Recurrent Childhood Small Noncleaved Cell 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, Recurrent/Refractory Childhood Hodgkin Lymphoma, Refractory Anemia With Excess Blasts, Refractory Anemia With Excess Blasts in Transformation, Refractory Cytopenia With Multilineage Dysplasia, Refractory Hairy Cell Leukemia, Refractory Multiple Myeloma, Relapsing Chronic Myelogenous Leukemia, Secondary Acute Myeloid Leukemia, Small Intestine Lymphoma, Splenic Marginal Zone Lymphoma, T-cell Large Granular Lymphocyte Leukemia, Testicular Lymphoma, Waldenström Macroglobulinemia

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Trial Information

A Two Step Approach to Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation for High Risk Hematologic Malignancies


PRIMARY OBJECTIVE:

1. To compare the rate of disease-free survival (DFS) at 1 year post hematopoietic stem cell
transplant (HSCT) in patients undergoing HSCT treated on this successor Thomas Jefferson
University (TJU) 2 Step reduced intensity conditioning (RIC) haploidentical regimen and
compare it with that of the initial 2 Step RIC regimen.

SECONDARY OBJECTIVES:

1. To assess the 100 day regimen-related mortality (RRM) in patients undergoing HSCT on
this treatment protocol.

2. To determine the incidence and severity of graft-versus-host disease (GVHD) in patients
undergoing treatment on this regimen.

3. To evaluate engraftment rates and lymphoid reconstitution in patients treated on this
trial.

4. To assess overall survival at 1 and 3 years past HSCT in patients treated on this
trial.

OUTLINE:

REDUCED INTENSITY CONDITIONING: Patients receive fludarabine phosphate intravenously (IV)
over 60 minutes on days -15 to -12, thiotepa IV over 2 hours on days -15 to -13, donor
lymphocyte infusion (DLI) on day -6, and cyclophosphamide IV over 2 hours on days -3 and -2.
Patients also undergo total-body irradiation (TBI) on day -10.

TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant (PBSCT) on day
0.

GVHD PROPHYLAXIS: Patients receive tacrolimus IV on days -1 to 42 followed by taper and
mycophenolate mofetil IV twice daily (BID) on days -1 to 28.

After completion of study treatment, patients are followed up periodically.


Inclusion Criteria:



1. Any patient with a high-risk hematologic or oncologic diagnosis in which allogeneic
HSCT is thought to be beneficial, and in whom front-line therapy has already been
applied. High risk is defined as:

1. Acute myeloid leukemia with high risk features as defined by:

- Age greater than or equal to 60

- Secondary AML (prior therapy or hematologic malignancy)

- Normal cytogenetics but FLT3/ITD positive

- Any relapse or primary refractory disease

- Greater than 3 cytogenetic abnormalities or any one of the following
cytogenetic abnormalities: -5/del(5q), -7/del(7q),
Abn(9q),(11q),(3q),(21q),(17p),t(6;9), t(6;11), t(11;19),
+8,del(12p),inv(3),t(10;11),-17, 11q 23

- Any single autosomal monosomy

2. Acute lymphoid leukemia in 1st or 2nd morphological remission. ALL with any
morphological evidence of disease will not be eligible.

3. Myelodysplasia (MDS) other than refractory anemia (RA), refractory anemia with
rare sideroblasts (RARS), or isolated 5q- syndrome subtypes.

4. Hodgkin's or Non-Hodgkin's lymphoma in 2nd or greater remission or with
persistent disease.

5. Myeloma with evidence of persistent disease after front-line therapy.

6. Chronic myeloid leukemia (CML) resistant to signal transducer inhibitor (STI)
therapy

7. Myelofibrosis and CMML

8. Essential Thrombocytopenia or Polycythemia Vera with current or past evidence of
evolution to acute leukemia

9. Any hematological malignancy not cited above which is thought to be high-risk
with increased chance of post HSCT relapse. Patients in this category require
specific approval of the PI and the TJU BMT attending physician group for
entrance.

2. Patients must have a related donor who is at least a 4 antigen match at the Human
Leukocyte Antigen (HLA)-A; B; C; DR loci.

3. Patients must adequate organ function:

1. Left ventricular end diastolic function (LVEF) of >50%

2. Diffusion Lung Capacity of Oxygen (DLCO) >50% of predicted corrected for
hemoglobin

3. Adequate liver function as defined by a serum bilirubin <1.8, aspartate
aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5X upper limit of
normal

4. Creatinine Clearance of ≥ 60 mL/min

4. Performance status ≥ 80% (TJU Karnofsky) for patients ≥ 60 years old or ≥70% for
patients < 60.

5. Hematopoietic cell transplant-comorbidity index (HCT-CI) Score ≤ 4 points for
patients ≥ 60 years old or ≤ 5 points for patients < 60.

6. Patients must be willing to use contraception if they have childbearing potential

7. Able to give informed consent

8. No previous radiation history that negates the ability to safely receive 2 Gy of TBI
as determined by the radiation oncologist and the study co-investigator responsible
for the patient

Exclusion Criteria:

1. Performance status < 80% (TJU Karnofsky) for patients ≥ 60 years old or <70% for
patients < 60.

2. HCT-CI Score > 4 points for patients ≥ 60 years old or > 5 points for patients < 60.

3. HIV positive

4. Active involvement of the central nervous system with malignancy

5. Inability to obtain informed consent

6. Pregnancy

7. Patients with life expectancy of < 6 months for reasons other than their underlying
hematologic/oncologic disorder

8. Patients who have received alemtuzumab within 8 weeks of the transplant admission, or
who have recently received horse or rabbit ant-thymocyte globulin and have an ATG
level of > 2 ugm/ml

9. Patients with evidence of another malignancy, exclusive of a skin cancer that
requires only local treatment, should not be enrolled on this protocol

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Disease-free survival (DFS)

Outcome Description:

The primary null hypothesis is that 1 year DFS rate is at most 35%. 35% is the rounded number (actual 36%) representing the DFS at 1 year of patients treated on the initial TJU 2 Step RIC HSCT trial and consistent with the outcome of patients treated on similar protocols outside of our institution.

Outcome Time Frame:

1 year

Safety Issue:

No

Principal Investigator

Dolores Grosso, RN, CRNP, DNP

Investigator Role:

Principal Investigator

Investigator Affiliation:

Thomas Jefferson University

Authority:

United States: Food and Drug Administration

Study ID:

12D.501

NCT ID:

NCT01760655

Start Date:

January 2013

Completion Date:

January 2020

Related Keywords:

  • Accelerated Phase Chronic Myelogenous Leukemia
  • Adult Acute Lymphoblastic Leukemia in Remission
  • Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
  • Adult Acute Myeloid Leukemia With Del(5q)
  • Adult Nasal Type Extranodal NK/T-cell Lymphoma
  • Anaplastic Large Cell Lymphoma
  • Angioimmunoblastic T-cell Lymphoma
  • Blastic Phase Chronic Myelogenous Leukemia
  • Childhood Acute Lymphoblastic Leukemia in Remission
  • Childhood Burkitt Lymphoma
  • Childhood Chronic Myelogenous Leukemia
  • Childhood Diffuse Large Cell Lymphoma
  • Childhood Immunoblastic Large Cell Lymphoma
  • Childhood Myelodysplastic Syndromes
  • Childhood Nasal Type Extranodal NK/T-cell Lymphoma
  • Chronic Myelomonocytic Leukemia
  • Chronic Phase Chronic Myelogenous Leukemia
  • Cutaneous B-cell Non-Hodgkin Lymphoma
  • de Novo Myelodysplastic Syndromes
  • Essential Thrombocythemia
  • Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
  • Hepatosplenic T-cell Lymphoma
  • Intraocular Lymphoma
  • Juvenile Myelomonocytic Leukemia
  • Nodal Marginal Zone B-cell Lymphoma
  • Noncutaneous Extranodal Lymphoma
  • Peripheral T-cell Lymphoma
  • Polycythemia Vera
  • Post-transplant Lymphoproliferative Disorder
  • Previously Treated Myelodysplastic Syndromes
  • Primary Myelofibrosis
  • 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 Childhood Acute Myeloid Leukemia
  • Recurrent Childhood Anaplastic Large Cell Lymphoma
  • Recurrent Childhood Grade III Lymphomatoid Granulomatosis
  • Recurrent Childhood Large Cell Lymphoma
  • Recurrent Childhood Lymphoblastic Lymphoma
  • Recurrent Childhood Small Noncleaved Cell 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
  • Recurrent/Refractory Childhood Hodgkin Lymphoma
  • Refractory Anemia With Excess Blasts
  • Refractory Anemia With Excess Blasts in Transformation
  • Refractory Cytopenia With Multilineage Dysplasia
  • Refractory Hairy Cell Leukemia
  • Refractory Multiple Myeloma
  • Relapsing Chronic Myelogenous Leukemia
  • Secondary Acute Myeloid Leukemia
  • Small Intestine Lymphoma
  • Splenic Marginal Zone Lymphoma
  • T-cell Large Granular Lymphocyte Leukemia
  • Testicular Lymphoma
  • Waldenström Macroglobulinemia
  • Congenital Abnormalities
  • Primary Myelofibrosis
  • Anemia
  • Anemia, Refractory
  • Anemia, Refractory, with Excess of Blasts
  • Blast Crisis
  • Burkitt Lymphoma
  • 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, Myeloid, Accelerated Phase
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Leukemia, Myeloid, Chronic-Phase
  • 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
  • Polycythemia
  • Polycythemia Vera
  • Sezary Syndrome
  • Thrombocythemia, Essential
  • 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
  • Anemia, Aplastic
  • Lymphoma, Mantle-Cell
  • Leukemia, Myelomonocytic, Juvenile
  • Hematologic Neoplasms
  • Thrombocytosis
  • Leukemia, Large Granular Lymphocytic

Name

Location

Thomas Jefferson UniversityPhiladelphia, Pennsylvania  19107-6541