Trial record 9 of 218 for:    Open Studies | "Leukemia, Myelogenous, Chronic, BCR-ABL Positive"

Reduced-Intensity Conditioning Before Donor Stem Cell Transplant in Treating Patients With High-Risk Hematologic Malignancies

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Thomas Jefferson University
Sponsor:
Information provided by (Responsible Party):
Thomas Jefferson University
ClinicalTrials.gov Identifier:
NCT01760655
First received: January 2, 2013
Last updated: August 5, 2014
Last verified: August 2014
  Purpose

This clinical trial studies reduced-intensity conditioning before donor stem cell transplant in treating patients with high-risk hematologic malignancies. Giving low-doses of chemotherapy and total-body irradiation before a donor stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect.


Condition Intervention Phase
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
Drug: Fludarabine phosphate
Drug: Thiotepa
Radiation: Total body irradiation
Biological: Therapeutic allogeneic lymphocytes
Drug: Cyclophosphamide
Procedure: Allogeneic hematopoietic stem cell transplantation (HSCT)
Procedure: Peripheral blood stem cell transplantation
Drug: Tacrolimus
Drug: Mycophenolate mofetil
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Two Step Approach to Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation for High Risk Hematologic Malignancies

Resource links provided by NLM:

Genetic and Rare Diseases Information Center resources: Leukemia, Myeloid Chronic Myeloid Leukemia Myelodysplastic Syndromes Lymphosarcoma Lymphoma, Small Cleaved-cell, Diffuse Acute Lymphoblastic Leukemia Multiple Myeloma Hodgkin Lymphoma Waldenstrom Macroglobulinemia Acute Myelocytic Leukemia Acute Non Lymphoblastic Leukemia Acute Myeloid Leukemia, Adult Follicular Lymphoma Hodgkin Lymphoma, Childhood B-cell Lymphomas Myelofibrosis Juvenile Myelomonocytic Leukemia Burkitt Lymphoma Lymphoma, Large-cell Lymphomatoid Granulomatosis Lymphoma, Large-cell, Immunoblastic Plasmablastic Lymphoma Lymphoblastic Lymphoma Small Non-cleaved Cell Lymphoma Anaplastic Large Cell Lymphoma Chronic Lymphocytic Leukemia Leukemia, B-cell, Chronic Chronic Myelomonocytic Leukemia Acute Lymphoblastic Leukemia, Childhood Acute Myeloid Leukemia, Childhood Mantle Cell Lymphoma Cutaneous T-cell Lymphoma Peripheral T-cell Lymphoma Polycythemia Vera Essential Thrombocythemia Leukemia, T-cell, Chronic Angioimmunoblastic T-cell Lymphoma Angioimmunoblastic Lymphadenopathy With Dysproteinemia Hairy Cell Leukemia Mycosis Fungoides Sezary Syndrome Large Granular Lymphocyte Leukemia Chronic Myeloproliferative Disorders Myelodysplastic/myeloproliferative Disease
U.S. FDA Resources

Further study details as provided by Thomas Jefferson University:

Primary Outcome Measures:
  • Disease-free survival (DFS) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Overall survival [ Time Frame: 1 year and 3 years ] [ Designated as safety issue: No ]
  • Incidence of Regimen Related Toxicity [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]
    Graded according to the National Cancer Institute (NCI) Common Toxicity Criteria version 4.0

  • Immune reconstitution [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]
  • Incidence and degree of GVHD [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]
  • Engraftment rates [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 50
Study Start Date: December 2012
Estimated Study Completion Date: January 2020
Estimated Primary Completion Date: January 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (RIC and stem cell transplant)

REDUCED INTENSITY CONDITIONING: Patients receive fludarabine phosphate 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 TBI on day -10.

TRANSPLANT: Patients undergo allogeneic PBSCT on day 0.

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

Drug: Fludarabine phosphate
Given IV
Other Names:
  • Fludarabine
  • Fludara
Drug: Thiotepa
Given IV
Other Names:
  • ThioTEPA
  • N,N'N'-triethylenethiophosphoramide
  • 1,1',1''-phosphorothioyltriaziridine
Radiation: Total body irradiation
Undergo TBI
Other Name: TBI
Biological: Therapeutic allogeneic lymphocytes
Undergo donor lymphocyte infusion
Other Names:
  • Allogeneic Lymphocytes
  • ALLOLYMPH
Drug: Cyclophosphamide
Given IV
Other Names:
  • Endoxan
  • Cytoxan
  • Neosar
  • Procytox
  • Revimmune
  • (RS)-N,N-bis(2-chloroethyl)-1,3,2-oxazaphosphinan-2-amine 2-oxide
  • Lyophilizedcytoxan
Procedure: Allogeneic hematopoietic stem cell transplantation (HSCT)
Undergo allogeneic PBSCT
Procedure: Peripheral blood stem cell transplantation
Undergo allogeneic PBSCT
Other Names:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • peripheral blood stem cell transplantation
Drug: Tacrolimus
Given IV
Other Names:
  • FK-506
  • fujimycin
  • Prograf
  • Advagraf
  • Protopic
Drug: Mycophenolate mofetil
Given IV
Other Names:
  • MMF
  • CellCept
  • Myfortic

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01760655

Contacts
Contact: Dolores Grosso, RN, CRNP, DNP 215-955-8874
Contact: Donna Zuccarello 215-955-6612

Locations
United States, Pennsylvania
Thomas Jefferson University Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Dolores Grosso, RN, CRNP, DNP    215-955-8874      
Contact: Donna Zuccarello    215-955-6612      
Principal Investigator: Dolores Grosso, RN, CRNP, DNP         
Principal Investigator: Neal Flomenberg, MD         
Sub-Investigator: S. Onder Alpdogan, MD         
Sub-Investigator: Matthew Carabasi, MD         
Sub-Investigator: Joanne Filicko-O'Hara, MD         
Sub-Investigator: Margaret Kasner, MD         
Sub-Investigator: William O'Hara, PharmD         
Sub-Investigator: Ubaldo Outschoorn Martinez, MD         
Sub-Investigator: John Wagner, MD         
Sub-Investigator: Mark Weiss, MD         
Sponsors and Collaborators
Thomas Jefferson University
Investigators
Principal Investigator: Dolores Grosso, RN, CRNP, DNP Thomas Jefferson University
Principal Investigator: Neal Flomenberg, MD Thomas Jefferson University
  More Information

No publications provided

Responsible Party: Thomas Jefferson University
ClinicalTrials.gov Identifier: NCT01760655     History of Changes
Other Study ID Numbers: 12D.501, 2012-67
Study First Received: January 2, 2013
Last Updated: August 5, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
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, Myeloid, Chronic-Phase
Leukemia, Myelomonocytic, Chronic
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphomatoid Granulomatosis
Lymphoproliferative Disorders
Waldenstrom Macroglobulinemia
Multiple Myeloma
Neoplasms, Plasma Cell

ClinicalTrials.gov processed this record on August 19, 2014