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Trial record 18 of 94 for:    Open Studies | "Epstein-Barr Virus Infections"

Study of Infusion of Blood Cells (Lymphocytes) to Stimulate the Immune System to Fight Leukemia/Lymphoma (273)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2013 by Brown University
Sponsor:
Information provided by (Responsible Party):
Peter Quesenberry, Brown University
ClinicalTrials.gov Identifier:
NCT01685606
First received: September 12, 2012
Last updated: August 8, 2013
Last verified: August 2013
  Purpose

The study of whether an infusion of blood cells called lymphocytes from a donor can stimulate the immune system to fight your leukemia/lymphoma.


Condition Intervention Phase
Mantle Cell Lymphoma
Diffuse Large Cell Lymphoma
Burkitts Lymphoma
T Cell Lymphomas
Acute Myeloid Leukemia/Acute Lymphoblastic Leukemia
Biological: cellular immunotherapy
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: BrUOG 273:Cellular Immunotherapy For Refractory Hematological Malignancies:A Brown University Oncology Research Group Study

Resource links provided by NLM:


Further study details as provided by Brown University:

Primary Outcome Measures:
  • To assess the response rate of cellular immune therapy with HLA haploidentical peripheral blood pheresed cells in patients with relapsed/refractory hematological malignancies. [ Time Frame: 8 weeks after infusion then 6 months after and every 4 months for approximately 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To assess the time-to-progression, progression-free survival and overall survival for patients with relapsed/refractory hematologic malignances following HLA haploidentical cellular therapy. [ Time Frame: 8 weeks after infusion then 6 months and every 4 months for approximately 2 years ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • To evaluate the rate of dose limiting toxicities of HLA haploidentical peripheral blood pheresed cellular infusions. [ Time Frame: 30 days and 16 weeks after infusion ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 25
Study Start Date: March 2013
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: cellular immunotherapy
A minimum of 1x108 CD3+ cells and maximum of 2x108 CD3+ cells/kg from a haploidentical donor will be infused, irrespective of the number of CD34+ cells.
Biological: cellular immunotherapy
A minimum of 1x108 CD3+ cells and maximum of 2x108 CD3+ cells/kg from a haploidentical donor irrespective of the number of CD34+ cells will be infused.

Detailed Description:

There have been important advances in the modulation of the immune system for the treatment of hematologic malignancies and solid tumors.

This protocol will build upon these previous observations as follows:

  • Haploidentical peripheral blood pheresed cells will be used at 1-2x108 CD3 cells/kg.
  • Total body radiation will not be utilized.

    • This modification may more effectively activate the recipient's immune system to attack their hematological malignancy by not damaging the recipient's immune cells prior to cellular infusion. Safety should be improved since the risk of graft versus host disease should be greatly reduced as the host's immune system will not be conditioned.
  • G-CSF priming will not be used.

    • In our first clinical trial, G-CSF priming was not used for matched transplants. Our second trial did employ G-CSF priming in the haplo-identical setting. Previous data has cited a role for G-CSF in stimulation of invariant NK cells with enhanced GVL effects11. However, our most recent laboratory data with unprimed PBMC has shown effective cell kill activity without the addition of G-CSF. As G-CSF would be administered to healthy volunteers, the unclear benefit of the addition of this cytokine is offset by the potential side effects such as headache, fever, and bone pain. G-CSF mobilization serves to shift the response from a TH1 to TH2 through the increased production of T regulatory cells. The end result would be a decrease in immune stimulation. Since the goal of this study is to NOT have engraftment, the manipulation of the donor cells to dampen the host versus tumor stimulation is not needed nor desired. Furthermore, since this protocol is not a stem cell transplant, stem cells do not need to be mobilized with G-CSF.

It is important to note that the proposed study is not a stem cell transplant study. In the situation of stem cell transplants, the goal of the procedure is to have engraftment, or sustainable donor chimerism in the marrow to provide hematopoietic reconstitution as well as immunologic reconstitution. In this study, we are evaluating the use of donor lymphocytes (not stem cells) to stimulate an immune response of the recipients' immune system.

  Eligibility

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

Inclusion Criteria:

  • Histologic confirmation of hematological malignancy consisting of the following leukemias/lymphomas:
  • Mantle cell lymphoma with Ki-67>30%
  • Diffuse Large Cell Lymphoma
  • Burkitts Lymphoma
  • Systemic T Cell Lymphomas
  • Acute Myeloid Leukemia
  • Acute Lymphoblastic Leukemia
  • Recurrence or progression of hematological malignancy after at least 1 prior standard treatment with progression within 6 months from last treatment.
  • No curative treatment option is available.

    -> 4-weeks since prior chemotherapy or radiation to cellular therapy infusion. (Hydroxyurea may be utilized up to 48 hours prior to initiation of treatment on this protocol).

  • Age equal to or greater than 18 years.
  • Patients with a history of invasive second malignancy unless disease free for > 5 years.
  • Patients must have an expected life expectancy of at least 2 months at the time of initiation of treatment.
  • No active systemic infection.
  • Patients who have relapsed after standard autologous stem cell infusion are eligible as long as they meet all inclusion criteria and no exclusion criteria. These patients must be out more than 6 months from cell infusion to be eligible for enrollment.
  • DLCO > 40% with no symptomatic pulmonary disease.
  • LVEF > 40% by MUGA or echocardiogram.
  • Creatinine < 2.0 mg/dl. Total bilirubin less than 1.5x the upper limit of normal (ULN), AST < 3x ULN.
  • Non-pregnant and willing to use appropriate birth control during the duration of the study period.

Exclusion Criteria:

  • Evidence of HIV infection.
  • Any uncontrolled severe, concurrent illness which in the opinion of the treating physician would make this protocol treatment unreasonably hazardous for the patient.
  • Oxygen dependent obstructive pulmonary disease.
  • Failure to demonstrate adequate compliance with medical therapy and follow-up.
  • Significant medical or psychiatric illness that would impair the ability to participate in protocol therapy.
  • For women of reproductive potential, refusal to use effective form of contraception.
  • Previous allogeneic stem cell transplant
  • Patients who have had previous purine analog (fludarabine, pentostatin, 2-CDA) -Patients with chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL), multiple myeloma, and indolent lymphoma (follicular lymphoma, marginal zone lymphoma)
  • Patients with HLA antibodies to donor HLA type.
  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: NCT01685606

Contacts
Contact: Kayla Rosati 401-863-3000 Kayla_Rosati@brown.edu

Locations
United States, Rhode Island
Rhode Island Hospital Recruiting
Providence, Rhode Island, United States, 02903
Contact: Peter Quesenberry, MD    401-863-3000      
Principal Investigator: Peter Quesenberry, MD         
Sub-Investigator: Eric Winer, MD         
Sub-Investigator: John Reagan, MD         
Sub-Investigator: James Butera, MD         
Sub-Investigator: Jorge Castillo, MD         
Sub-Investigator: Loren Fast, MD         
Sub-Investigator: Howard Safran, MD         
The Miriam Hospital Recruiting
Providence, Rhode Island, United States, 02903
Contact: Kayla Rosati    401-863-3000    kayla_rosati@brown.edu   
Contact: Group         
Sponsors and Collaborators
Brown University
Investigators
Principal Investigator: Peter Quesenberry, MD Brown University
  More Information

No publications provided

Responsible Party: Peter Quesenberry, Principal Investigator, Brown University
ClinicalTrials.gov Identifier: NCT01685606     History of Changes
Other Study ID Numbers: BrUOG 273
Study First Received: September 12, 2012
Last Updated: August 8, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Brown University:
Leukemia
Lymphoma
Mantle cell
DLBCL
DLBC
Diffuse large B cell
T cell
AML
ALL

Additional relevant MeSH terms:
Epstein-Barr Virus Infections
Burkitt Lymphoma
Leukemia
Leukemia, Lymphoid
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Lymphoma
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Mantle-Cell
Lymphoma, T-Cell
Precursor Cell Lymphoblastic Leukemia-Lymphoma
DNA Virus Infections
Herpesviridae Infections
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Experimental
Tumor Virus Infections
Virus Diseases

ClinicalTrials.gov processed this record on November 25, 2014