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

Primary Purpose

Mantle Cell Lymphoma, Diffuse Large Cell Lymphoma, Burkitts Lymphoma

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
cellular immunotherapy
Sponsored by
Brown University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mantle Cell Lymphoma focused on measuring Leukemia, Lymphoma, Mantle cell, DLBCL, DLBC, Diffuse large B cell, T cell, AML, ALL

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Rhode Island Hospital
  • The Miriam Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

cellular immunotherapy

Arm 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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
September 12, 2012
Last Updated
February 23, 2022
Sponsor
Brown University
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1. Study Identification

Unique Protocol Identification Number
NCT01685606
Brief Title
Study of Infusion of Blood Cells (Lymphocytes) to Stimulate the Immune System to Fight Leukemia/Lymphoma
Acronym
273
Official Title
BrUOG 273:Cellular Immunotherapy For Refractory Hematological Malignancies:A Brown University Oncology Research Group Study
Study Type
Interventional

2. Study Status

Record Verification Date
February 2022
Overall Recruitment Status
Terminated
Why Stopped
Lack of accrual and low efficacy
Study Start Date
March 2013 (undefined)
Primary Completion Date
June 2015 (Actual)
Study Completion Date
June 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Brown University

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mantle Cell Lymphoma, Diffuse Large Cell Lymphoma, Burkitts Lymphoma, T Cell Lymphomas, Acute Myeloid Leukemia/Acute Lymphoblastic Leukemia
Keywords
Leukemia, Lymphoma, Mantle cell, DLBCL, DLBC, Diffuse large B cell, T cell, AML, ALL

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Arm Title
cellular immunotherapy
Arm Type
Experimental
Arm 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.
Intervention Type
Biological
Intervention Name(s)
cellular immunotherapy
Intervention Description
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.
Primary Outcome Measure Information:
Title
Overall Response Rate of Cellular Immune Therapy With HLA Haploidentical Peripheral Blood Pheresed Cells in Patients With Relapsed/Refractory Hematological Malignancies.
Description
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.
Time Frame
8 weeks after infusion then 6 months after and every 4 months for approximately 2 years
Secondary Outcome Measure Information:
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter Quesenberry, MD
Organizational Affiliation
Brown University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Rhode Island Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States
Facility Name
The Miriam Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
23782682
Citation
Reagan JL, Fast LD, Safran H, Nevola M, Winer ES, Castillo JJ, Butera JN, Quesenberry MI, Young CT, Quesenberry PJ. Cellular immunotherapy for refractory hematological malignancies. J Transl Med. 2013 Jun 19;11:150. doi: 10.1186/1479-5876-11-150.
Results Reference
derived

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

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