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

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Brief Title

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

Official Title

BrUOG 273:Cellular Immunotherapy For Refractory Hematological Malignancies:A Brown University Oncology Research Group Study

Brief Summary

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

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.

        -  Granulocyte-colony stimulating factor (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 Natural Killer(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.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Overall Response Rate of Cellular Immune Therapy With HLA Haploidentical Peripheral Blood Pheresed Cells in Patients With Relapsed/Refractory Hematological Malignancies.

Secondary Outcome

 To Evaluate the Rate of Dose Limiting Toxicities of HLA Haploidentical Peripheral Blood Pheresed Cellular Infusions.

Condition

Mantle Cell Lymphoma

Intervention

cellular immunotherapy

Study Arms / Comparison Groups

 cellular immunotherapy
Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

6

Start Date

March 2013

Completion Date

June 2015

Primary Completion Date

June 2015

Eligibility 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.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Peter Quesenberry, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT01685606

Organization ID

BrUOG 273


Responsible Party

Principal Investigator

Study Sponsor

Brown University


Study Sponsor

Peter Quesenberry, MD, Principal Investigator, Brown University


Verification Date

July 2015