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A Two Step Approach to Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation for Patients With Hematologic Malignancies


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Adult Acute Lymphoblastic Leukemia in Remission, 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 Nasal Type Extranodal NK/T-cell Lymphoma, Aplastic Anemia, Childhood Acute Lymphoblastic Leukemia in Remission, Childhood Acute Myeloid Leukemia in Remission, Childhood Myelodysplastic Syndromes, Chronic Eosinophilic Leukemia, Chronic Myelomonocytic Leukemia, Chronic Neutrophilic Leukemia, Essential Thrombocythemia, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Juvenile Myelomonocytic Leukemia, Mastocytosis, Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable, Nodal Marginal Zone B-cell Lymphoma, Polycythemia Vera, Previously Treated Myelodysplastic Syndromes, Primary Myelofibrosis, Recurrent Adult Acute Lymphoblastic Leukemia, Recurrent Adult Acute Myeloid Leukemia, Recurrent Adult Diffuse Small Cleaved Cell Lymphoma, Recurrent Adult Grade III Lymphomatoid Granulomatosis, Recurrent Adult Hodgkin Lymphoma, Recurrent Childhood Acute Lymphoblastic Leukemia, Recurrent Childhood Acute Myeloid Leukemia, Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Marginal Zone Lymphoma, Recurrent Mycosis Fungoides/Sezary Syndrome, Recurrent Small Lymphocytic Lymphoma, Recurrent/Refractory Childhood Hodgkin Lymphoma, Refractory Anemia, Refractory Anemia With Ringed Sideroblasts, Refractory Hairy Cell Leukemia, Refractory Multiple Myeloma, Secondary Myelodysplastic Syndromes, Splenic Marginal Zone Lymphoma, T-cell Large Granular Lymphocyte Leukemia, Waldenström Macroglobulinemia

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Trial Information

A Two Step Approach to Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation for Patients With Hematologic Malignancies


PRIMARY OBJECTIVES:

I. To compare the overall survival (OS) rate at 2 years post treatment using the Jefferson 2
step reduced intensity conditioning (RIC) approach in patients with haploidentical family
donors with hematological malignancies in morphological or radiographic remission or with
chemosensitive, indolent diseases to historical OS rates in similar populations after RIC
matched donor HSCT as reported in the literature.

SECONDARY OBJECTIVES:

I. To compare the treatment-related mortality (TRM) rate at 2 years for patients treated on
this study to the historical TRM rates of patients undergoing RIC matched-sibling HSCT as
reported in the literature.

II. To compare the 2 year relapse rates and relapse related mortality of patients with
myeloid diseases to that of patients with lymphoid diseases who are treated on this Thomas
Jefferson University (TJU) RIC 2 step approach.

III. To determine the incidence and severity of graft-versus-host disease (GVHD) in patients
undergoing treated on the TJU RIC 2 step approach.

IV. To evaluate engraftment rates and lymphoid reconstitution in patients treated on the TJU
RIC 2 step approach.

V. To evaluate the incidence of TRM at 100 days in patients treated on the TJU RIC 2 step
approach.

OUTLINE:

REDUCED INTENSITY CONDITIONING: Patients receive fludarabine phosphate intravenously (IV)
over 60 minutes on days -11 to -8 and thiotepa IV over 2 hours on days -11 to -9. Patients
undergo total body irradiation (TBI) on day -6. Patients also receive cyclophosphamide IV
over 2 hours on days -3 and -2.

TRANSPLANTATION: Patients undergo donor lymphocyte infusion (DLI) on day -6 and cluster of
differentiation (CD)-34+ allogeneic peripheral blood stem cell transplantation (PBSCT) on
day 0.

GVHD PROPHYLAXIS: Beginning on day -1, patients receive tacrolimus IV or orally (PO) with
taper beginning on day 42. Patients also receive mycophenolate mofetil IV twice daily (BID)
on days -1 to 28.

After completion of study treatment, patients are followed up periodically for 2 years.


Inclusion Criteria:



1. Any patient with hematologic or oncologic diagnosis in which allogeneic HSCT is
thought to be beneficial, and in whom front-line therapy has already been applied.
Patients treated on this protocol will be without morphological evidence of disease
(complete remission or "CR"), or if the patient has evidence of disease, the patient
must have had at least a good partial response (PR) to the most recent therapy and
the disease must be chemoresponsive.

2. Patients treated on this study will have:

- Acute leukemia in 1st or 2nd CR

- MDS (myelodysplastic syndrome), specific subtypes of RA (refractory anemia) or
RARS (refractory anemia with ringed sideroblasts) subtypes.

- Hodgkin or Indolent Non-Hodgkin's lymphoma with chemosensitive disease

- Myeloma without morphological evidence of disease, or a deep PR to the most
recent therapy

- Myeloproliferative disorders with at least a PR to current therapy

- Aplastic Anemia

- A hematological or oncological disease (not listed) that meets the criteria
reviewed above (in CR or with a good PR).

3. Patients must have a related donor who is HLA mismatched at 2, 3, or 4 antigens at
the HLA-A; B; C; DR loci in the GVHD direction. (Patients with related donors who are
HLA identical or are a 1-antigen mismatch may be treated on this therapeutic
approach, but will have their outcomes will not be part of the statistical aims of
the study (see Summary section).

4. Patients must adequate organ function:

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

- DLCO (Diffusing Capacity of the Lung for Carbon Monoxide ) ≥50% of predicted
corrected for hemoglobin

- Adequate liver function as defined by a serum bilirubin <1.8, AST or ALT < 2.5X
upper limit of normal

- Creatinine Clearance of ≥ 60 mL/min

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

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

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

8. Able to give informed consent

Exclusion Criteria:

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

2. Hematopoietic Cell Transplant-Comorbidity Index (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 anti-thymocyte globulin and have an
anti-thymocyte globulin 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: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall Survival (OS) in patients with haploidentical family donors with hematological malignancies in morphological or radiographic remission or with chemosensitive, indolent diseases

Outcome Description:

The primary null hypothesis is that 2 year OS rate is at most 35%. This hypothesis will be rejected if the 95% confidence interval for year OS rate computed from the estimated Kaplan-Meier survival curves will be entirely above 0.35.

Outcome Time Frame:

At 2 years

Safety Issue:

No

Principal Investigator

Dolores Grosso, DNP, CRNP

Investigator Role:

Principal Investigator

Investigator Affiliation:

Thomas Jefferson University

Authority:

United States: Food and Drug Administration

Study ID:

11D.247

NCT ID:

NCT01384513

Start Date:

August 2011

Completion Date:

July 2017

Related Keywords:

  • Adult Acute Lymphoblastic Leukemia in Remission
  • 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 Nasal Type Extranodal NK/T-cell Lymphoma
  • Aplastic Anemia
  • Childhood Acute Lymphoblastic Leukemia in Remission
  • Childhood Acute Myeloid Leukemia in Remission
  • Childhood Myelodysplastic Syndromes
  • Chronic Eosinophilic Leukemia
  • Chronic Myelomonocytic Leukemia
  • Chronic Neutrophilic Leukemia
  • Essential Thrombocythemia
  • Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
  • Juvenile Myelomonocytic Leukemia
  • Mastocytosis
  • Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable
  • Nodal Marginal Zone B-cell Lymphoma
  • Polycythemia Vera
  • Previously Treated Myelodysplastic Syndromes
  • Primary Myelofibrosis
  • Recurrent Adult Acute Lymphoblastic Leukemia
  • Recurrent Adult Acute Myeloid Leukemia
  • Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
  • Recurrent Adult Grade III Lymphomatoid Granulomatosis
  • Recurrent Adult Hodgkin Lymphoma
  • Recurrent Childhood Acute Lymphoblastic Leukemia
  • Recurrent Childhood Acute Myeloid Leukemia
  • Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
  • Recurrent Grade 1 Follicular Lymphoma
  • Recurrent Grade 2 Follicular Lymphoma
  • Recurrent Marginal Zone Lymphoma
  • Recurrent Mycosis Fungoides/Sezary Syndrome
  • Recurrent Small Lymphocytic Lymphoma
  • Recurrent/Refractory Childhood Hodgkin Lymphoma
  • Refractory Anemia
  • Refractory Anemia With Ringed Sideroblasts
  • Refractory Hairy Cell Leukemia
  • Refractory Multiple Myeloma
  • Secondary Myelodysplastic Syndromes
  • Splenic Marginal Zone Lymphoma
  • T-cell Large Granular Lymphocyte Leukemia
  • Waldenström Macroglobulinemia
  • Allogeneic HSCT
  • Hematopoietic stem cell transplantation
  • Congenital Abnormalities
  • Primary Myelofibrosis
  • Anemia
  • Anemia, Aplastic
  • Anemia, Refractory
  • Neoplasms
  • Hodgkin Disease
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Hairy Cell
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myelomonocytic, Chronic
  • Leukemia, Neutrophilic, Chronic
  • Lymphoma
  • Lymphoma, Follicular
  • Lymphoma, Non-Hodgkin
  • Lymphomatoid Granulomatosis
  • Waldenstrom Macroglobulinemia
  • Mastocytosis
  • Urticaria Pigmentosa
  • Mastocytoma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Mycoses
  • Mycosis Fungoides
  • Myelodysplastic Syndromes
  • Preleukemia
  • Leukemia, Myelomonocytic, Acute
  • Myeloproliferative Disorders
  • Polycythemia
  • Polycythemia Vera
  • Sezary Syndrome
  • Thrombocythemia, Essential
  • Lymphoma, B-Cell
  • Lymphoma, T-Cell
  • Lymphoma, T-Cell, Cutaneous
  • Hypereosinophilic Syndrome
  • Lymphoma, B-Cell, Marginal Zone
  • Lymphoma, Extranodal NK-T-Cell
  • Leukemia, Myelomonocytic, Juvenile
  • Hematologic Neoplasms
  • Thrombocytosis
  • Myelodysplastic-Myeloproliferative Diseases
  • Leukemia, Large Granular Lymphocytic

Name

Location

Thomas Jefferson UniversityPhiladelphia, Pennsylvania  19107-6541