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

This study is currently recruiting participants.
Verified November 2017 by Thomas Jefferson University ( Sidney Kimmel Cancer Center at Thomas Jefferson University )
Sponsor:
ClinicalTrials.gov Identifier:
NCT01760655
First Posted: January 4, 2013
Last Update Posted: November 10, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Thomas Jefferson University ( Sidney Kimmel Cancer Center at Thomas Jefferson University )
  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: Intervention Model: Single Group Assignment
Masking: None (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:


Further study details as provided by Thomas Jefferson University ( Sidney Kimmel Cancer Center at Thomas Jefferson University ):

Primary Outcome Measures:
  • Disease-free survival (DFS) [ Time Frame: 1 year ]
    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 ]
  • Incidence of Regimen Related Toxicity [ Time Frame: Up to 1 year ]
    Graded according to the National Cancer Institute (NCI) Common Toxicity Criteria version 4.0

  • Immune reconstitution [ Time Frame: Up to 1 year ]
  • Incidence and degree of GVHD [ Time Frame: Up to 1 year ]
  • Engraftment rates [ Time Frame: Up to 1 year ]

Estimated Enrollment: 50
Actual Study Start Date: December 24, 2012
Estimated Study Completion Date: January 2020
Estimated Primary Completion Date: December 2019 (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:
  • 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
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

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01760655


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

Locations
United States, Pennsylvania
Thomas Jefferson University Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Dolores Grosso, RN, CRNP, DNP    215-955-8874      
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
Sidney Kimmel Cancer Center at Thomas Jefferson University
Investigators
Principal Investigator: Dolores Grosso, RN, CRNP, DNP Thomas Jefferson University
Principal Investigator: Neal Flomenberg, MD Thomas Jefferson University
  More Information

Responsible Party: Sidney Kimmel Cancer Center at Thomas Jefferson University
ClinicalTrials.gov Identifier: NCT01760655     History of Changes
Other Study ID Numbers: 12D.501
2012-67 ( Other Identifier: CCRRC )
First Submitted: January 2, 2013
First Posted: January 4, 2013
Last Update Posted: November 10, 2017
Last Verified: November 2017

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No

Additional relevant MeSH terms:
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Lymphoma
Syndrome
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Multiple Myeloma
Lymphoma, Follicular
Anemia
Myelodysplastic Syndromes
Preleukemia
Lymphoma, Non-Hodgkin
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Hodgkin Disease
Lymphoma, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, B-Cell, Marginal Zone
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Large B-Cell, Diffuse
Burkitt Lymphoma
Lymphoma, T-Cell
Lymphoma, Large-Cell, Immunoblastic
Plasmablastic Lymphoma
Mycoses
Primary Myelofibrosis
Mycosis Fungoides
Sezary Syndrome
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic