273: Study of Infusion of Blood Cells (Lymphocytes) to Stimulate the Immune System to Fight Leukemia/Lymphoma
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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.
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Total body radiation will not be utilized.
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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.
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Granulocyte-colony stimulating factor (G-CSF) priming will not be used.
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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 Design
Arms and Interventions
| 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.
|
Outcome Measures
Primary Outcome Measures
- Overall Response Rate of Cellular Immune Therapy With HLA Haploidentical Peripheral Blood Pheresed Cells in Patients With Relapsed/Refractory Hematological Malignancies. [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.
Secondary Outcome Measures
- To Evaluate the Rate of Dose Limiting Toxicities of HLA Haploidentical Peripheral Blood Pheresed Cellular Infusions. [30 days and 16 weeks after infusion]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Histologic confirmation of hematological malignancy consisting of the following leukemias/lymphomas:
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Mantle cell lymphoma with Ki-67>30%
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Diffuse Large Cell Lymphoma
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Burkitts Lymphoma
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Systemic T Cell Lymphomas
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Acute Myeloid Leukemia
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Acute Lymphoblastic Leukemia
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Recurrence or progression of hematological malignancy after at least 1 prior standard treatment with progression within 6 months from last treatment.
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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).
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Age equal to or greater than 18 years.
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Patients with a history of invasive second malignancy unless disease free for > 5 years.
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Patients must have an expected life expectancy of at least 2 months at the time of initiation of treatment.
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No active systemic infection.
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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.
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DLCO > 40% with no symptomatic pulmonary disease.
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LVEF > 40% by MUGA or echocardiogram.
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Creatinine < 2.0 mg/dl. Total bilirubin less than 1.5x the upper limit of normal (ULN), AST < 3x ULN.
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Non-pregnant and willing to use appropriate birth control during the duration of the study period.
Exclusion Criteria:
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Evidence of HIV infection.
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Any uncontrolled severe, concurrent illness which in the opinion of the treating physician would make this protocol treatment unreasonably hazardous for the patient.
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Oxygen dependent obstructive pulmonary disease.
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Failure to demonstrate adequate compliance with medical therapy and follow-up.
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Significant medical or psychiatric illness that would impair the ability to participate in protocol therapy.
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For women of reproductive potential, refusal to use effective form of contraception.
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Previous allogeneic stem cell transplant
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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)
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Patients with HLA antibodies to donor HLA type.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Rhode Island Hospital | Providence | Rhode Island | United States | 02903 |
| 2 | The Miriam Hospital | Providence | Rhode Island | United States | 02903 |
Sponsors and Collaborators
- Brown University
Investigators
- Principal Investigator: Peter Quesenberry, MD, Brown University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BrUOG 273
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Cellular Immunotherapy |
|---|---|
| Arm/Group 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. 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. |
| Period Title: Overall Study | |
| STARTED | 6 |
| COMPLETED | 5 |
| NOT COMPLETED | 1 |
Baseline Characteristics
| Arm/Group Title | Cellular Immunotherapy |
|---|---|
| Arm/Group 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. 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. |
| Overall Participants | 5 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
2
40%
|
| >=65 years |
3
60%
|
| Age (years) [Mean (Full Range) ] | |
| Mean (Full Range) [years] |
66.2
|
| Sex: Female, Male (Count of Participants) | |
| Female |
3
60%
|
| Male |
2
40%
|
| Region of Enrollment (participants) [Number] | |
| United States |
5
100%
|
Outcome Measures
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Cellular Immunotherapy |
|---|---|
| Arm/Group 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. 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. |
| Measure Participants | 5 |
| Number [participants] |
1
20%
|
| Title | To Evaluate the Rate of Dose Limiting Toxicities of HLA Haploidentical Peripheral Blood Pheresed Cellular Infusions. |
|---|---|
| Description | |
| Time Frame | 30 days and 16 weeks after infusion |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Cellular Immunotherapy |
|---|---|
| Arm/Group 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. 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. |
| Measure Participants | 5 |
| Number [participants] |
0
0%
|
Adverse Events
| Time Frame | ||
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Cellular Immunotherapy | |
| Arm/Group 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. 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. | |
All Cause Mortality |
||
| Cellular Immunotherapy | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Cellular Immunotherapy | ||
| Affected / at Risk (%) | # Events | |
| Total | 6/6 (100%) | |
| Investigations | ||
| Albumin | 1/6 (16.7%) | 1 |
| ALT | 1/6 (16.7%) | 1 |
| anemia | 2/6 (33.3%) | 2 |
| AST | 1/6 (16.7%) | 1 |
| bone pain | 1/6 (16.7%) | 1 |
| ca | 1/6 (16.7%) | 1 |
| CRS (pt 3 included n, ha, r) | 1/6 (16.7%) | 1 |
| diarrhea | 1/6 (16.7%) | 1 |
| dizziness | 4/6 (66.7%) | 4 |
| Febrile Neutropenia | 1/6 (16.7%) | 1 |
| fever | 2/6 (33.3%) | 2 |
| Hypotension | 3/6 (50%) | 3 |
| tachycardia | 1/6 (16.7%) | 1 |
| infection | 1/6 (16.7%) | 1 |
| 1/6 (16.7%) | 1 | |
| Nausea | 1/6 (16.7%) | 1 |
| Neutropenia | 1/6 (16.7%) | 1 |
| pain-neck | 1/6 (16.7%) | 1 |
| PLT | 1/6 (16.7%) | 1 |
| creatinine | 1/6 (16.7%) | 1 |
| infection: wound | 1/6 (16.7%) | 2 |
| GI bleed | 1/6 (16.7%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| Cellular Immunotherapy | ||
| Affected / at Risk (%) | # Events | |
| Total | 6/6 (100%) | |
| Investigations | ||
| alk phos | 1/6 (16.7%) | 1 |
| anemia | 4/6 (66.7%) | 4 |
| anxiety | 1/6 (16.7%) | 1 |
| arthralgia | 1/6 (16.7%) | 1 |
| bleeding scrotum | 1/6 (16.7%) | 1 |
| bone pain | 1/6 (16.7%) | 1 |
| ca | 2/6 (33.3%) | 2 |
| diarrhea | 1/6 (16.7%) | 1 |
| cough | 2/6 (33.3%) | 2 |
| edema | 2/6 (33.3%) | 2 |
| epistaxis | 1/6 (16.7%) | 1 |
| erythema | 1/6 (16.7%) | 1 |
| eye stye Not graded pt 3 | 2/6 (33.3%) | 2 |
| fever | 2/6 (33.3%) | 2 |
| Hyperglycemia | 5/6 (83.3%) | 5 |
| K | 1/6 (16.7%) | 1 |
| Leukocytosis | 1/6 (16.7%) | 1 |
| Lymph | 4/6 (66.7%) | 4 |
| minor bleeding superficila leg lesions "minor" NG pt #3 | 1/6 (16.7%) | 1 |
| 2/6 (33.3%) | 2 | |
| Neutropenia | 3/6 (50%) | 3 |
| oral thrush | 1/6 (16.7%) | 1 |
| Phos | 2/6 (33.3%) | 2 |
| PLT | 1/6 (16.7%) | 1 |
| post nasal | 1/6 (16.7%) | 1 |
| segs/neuts | 1/6 (16.7%) | 1 |
| sinus pain Not graded pt 3 | 1/6 (16.7%) | 1 |
| sinus tach | 1/6 (16.7%) | 1 |
| Vomiting | 1/6 (16.7%) | 1 |
| WBC | 2/6 (33.3%) | 2 |
| cellulitis | 1/6 (16.7%) | 1 |
| fatigue | 1/6 (16.7%) | 1 |
| LE pain | 1/6 (16.7%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Peter Quesenberry |
|---|---|
| Organization | Brown University Oncology Research Group (BrUOG) |
| Phone | 4018633000 |
| kayla_rosati@brown.edu |
- BrUOG 273