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

February 23, 2022 updated by: Brown University

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

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

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

6

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Rhode Island Hospital
      • Providence, Rhode Island, United States, 02903
        • The Miriam Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall 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

Criteria for AML and ALL (adapted from Cheson et al.20)

Complete remission (CR) is defined as the presence of all of the following

  • Peripheral blood

    o No leukemic blasts present.

  • No extramedullary findings of leukemia or disappearance of such (i.e. CNS or soft tissue involvement)

  • Bone marrow

    • Cellularity >20% with baseline maturation.
    • No Auer rods
    • Less than 5% blast cells.
  • Complete blood counts and bone marrow normalization criteria must be met within one week of each other. Hematopoeitic recovery is an ANC > 1.0 x 109/L and platelet count > 100x109/L. No specific hemoglobin or hematocrit level is specified but the patient must be transfusion free.

Complete remission with incomplete recovery (CRi) is defined as the following:

  • Meets criteria for CR except
  • ANC < 1.0 x 109/L or platelet count < 100x109/L

Partial remission (PR).

• Must meet all criteria of a CR except that the bone marrow may contain 5-20% blasts.
8 weeks after infusion then 6 months after and every 4 months for approximately 2 years

Secondary Outcome Measures

Outcome Measure
Time Frame
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
30 days and 16 weeks after infusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Brown University

Investigators

  • Principal Investigator: Peter Quesenberry, MD, Brown University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2013

Primary Completion (Actual)

June 1, 2015

Study Completion (Actual)

June 1, 2015

Study Registration Dates

First Submitted

September 12, 2012

First Submitted That Met QC Criteria

September 12, 2012

First Posted (Estimate)

September 14, 2012

Study Record Updates

Last Update Posted (Actual)

March 4, 2022

Last Update Submitted That Met QC Criteria

February 23, 2022

Last Verified

February 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BrUOG 273

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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