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Cytokine-Treated Veto Cells in Treating Participants With Hematologic Malignancies Following Stem Cell Transplant

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ClinicalTrials.gov Identifier: NCT03622788
Recruitment Status : Not yet recruiting
First Posted : August 9, 2018
Last Update Posted : May 21, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
This phase I/II trial studies how well cytokine-treated veto cells work in treating participants with hematologic malignancies following stem cell transplant. Giving chemotherapy and total-body irradiation before a stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the participant, they may help the participant's bone marrow make stem cells, red blood cells, white blood cells, and platelets. cytokine-treated veto cells may help the transplanted donor cells to develop and grow in recipients without causing graft-versus-host-disease (GVHD - when transplanted donor tissue attacks the tissues of the recipient's body).

Condition or disease Intervention/treatment Phase
Acute Lymphoblastic Leukemia Acute Myeloid Leukemia Acute Myeloid Leukemia in Remission Aplastic Anemia Bone Marrow Failure Chronic Lymphocytic Leukemia Chronic Myelogenous Leukemia, BCR-ABL1 Positive Donor Follicular Lymphoma Hematopoietic Cell Transplantation Recipient Hodgkin Lymphoma Mantle Cell Lymphoma Myelodysplastic Syndrome Myeloproliferative Neoplasm Near Complete Response of Multiple Myeloma or Plasma Cell Leukemia Non-Hodgkin Lymphoma Partial Response of Multiple Myeloma or Plasma Cell Leukemia Plasma Cell Myeloma Biological: Anti-Thymocyte Globulin Drug: Cyclophosphamide Biological: Cytokine-treated Veto Cells Drug: Fludarabine Procedure: Peripheral Blood Stem Cell Transplantation Radiation: Total-Body Irradiation Phase 1 Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the optimal dose of anti-viral veto cells, defined as the dose which achieves engraftment without severe graft-vs-host disease (GVHD) at 42 days after non-myeloablative megadose T cell depleted haploidentical hematopoietic cell transplantation (HCT).

SECONDARY OBJECTIVES:

I. Toxicity. II. Response rate. III. Time to progression. IV. Infections. V. Immune reconstitution. VI. Overall survival up to 1 year.

OUTLINE: This is a dose-escalation study of cytokine-treated veto cells.

CONDITIONING REGIMEN: Participants receive anti-thymocyte globulin (ATG) intravenously (IV) over 4 hours on days -9 to -7 and fludarabine IV over 1 hour on days -6 to -3, then undergo total body irradiation (TBI) on day -1.

TRANSPLANT: Participants undergo peripheral blood stem cell transplantation (PBSCT) IV over 30-60 minutes on day 0.

GVHD PROPHYLAXIS: Participants receive cyclophosphamide IV over 3 hours on days +3 and +4 and cytokine-treated veto cells IV over 30-60 minutes on day +7.

After completion of stem cell transplant, participants are followed up once a week for 4 weeks, once a month for 3 months, and then periodically for one year.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Anti-Viral Central Memory CD8 Veto Cells in Haploidentical Hematopoietic Stem Cell Transplantation
Estimated Study Start Date : July 1, 2019
Estimated Primary Completion Date : July 1, 2021
Estimated Study Completion Date : July 1, 2021


Arm Intervention/treatment
Experimental: Treatment (chemotherapy, PBSCT, cytokine-treated veto cells)

CONDITIONING REGIMEN: Participants receive ATG IV over 4 hours on days -9 to -7, and fludarabine IV over 1 hour on days -6 to -3, then undergo TBI on day -1.

TRANSPLANT: Participants undergo PBSCT IV over 30-60 minutes on day 0.

GVHD PROPHYLAXIS: Participants receive cyclophosphamide IV over 3 hours on days +3 and +4 and cytokine-treated veto cells IV over 30-60 minutes on day +7.

Biological: Anti-Thymocyte Globulin
Given IV
Other Names:
  • Antithymocyte Globulin
  • Antithymocyte Serum
  • ATG
  • ATGAM
  • ATS
  • Thymoglobulin

Drug: Cyclophosphamide
Given IV
Other Names:
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CTX
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719

Biological: Cytokine-treated Veto Cells
Given IV
Other Name: Veto Cell (SY); Veto Cells (SY); Activated Veto T-cells (SY); Veto-enhanced Cytotoxic T-cell (SY); Veto-enhanced CTL (SY); Veto CD8-positive T-cells (SY); Activated Veto Cells (SY)

Drug: Fludarabine
Given IV
Other Name: Fluradosa

Procedure: Peripheral Blood Stem Cell Transplantation
Undergo PBSCT
Other Names:
  • PBPC transplantation
  • PBSCT
  • Peripheral Blood Progenitor Cell Transplantation
  • Peripheral Stem Cell Support
  • Peripheral Stem Cell Transplant
  • Peripheral Stem Cell Transplantation

Radiation: Total-Body Irradiation
Undergo TBI
Other Names:
  • Total Body Irradiation
  • Whole-Body Irradiation




Primary Outcome Measures :
  1. Optimal dose of donor-derived cytokine-treated veto cells [ Time Frame: Within 42 days of cytokine-treated veto cell infusion ]
    For the purpose of dose-finding, toxicity is defined as steroid resistant grade 3 or 4 graft-versus-host-disease (GVHD), or death from any cause, within 42 days of veto cell infusion.

  2. Efficacy of veto cells defined as the patient being alive and engrafted at day 42 post veto cell infusion. [ Time Frame: At day 42 post cytokine-treated veto cell infusion ]

Secondary Outcome Measures :
  1. Incidence of adverse events [ Time Frame: Up to 1 year ]
    Unadjusted distributions of time-to-event outcomes will be estimated using the method of Kaplan and Meier and their relationship to prognostic covariates and veto cell dose level will be evaluated by Bayesian piecewise exponential survival regression.

  2. Response rate [ Time Frame: Up to 1 year ]
    Unadjusted distributions of time-to-event outcomes will be estimated using the method of Kaplan and Meier and their relationship to prognostic covariates and veto cell dose level will be evaluated by Bayesian piecewise exponential survival regression.

  3. Time to progression [ Time Frame: Up to 1 year ]
    Unadjusted distributions of time-to-event outcomes will be estimated using the method of Kaplan and Meier and their relationship to prognostic covariates and veto cell dose level will be evaluated by Bayesian piecewise exponential survival regression.

  4. Infections [ Time Frame: Up to 1 year ]
    Unadjusted distributions of time-to-event outcomes will be estimated using the method of Kaplan and Meier and their relationship to prognostic covariates and veto cell dose level will be evaluated by Bayesian piecewise exponential survival regression.

  5. Immune reconstitution [ Time Frame: Up to 1 year ]
    Unadjusted distributions of time-to-event outcomes will be estimated using the method of Kaplan and Meier and their relationship to prognostic covariates and veto cell dose level will be evaluated by Bayesian piecewise exponential survival regression.

  6. Overall survival [ Time Frame: Up to 1 year ]
    Unadjusted distributions of time-to-event outcomes will be estimated using the method of Kaplan and Meier and their relationship to prognostic covariates and veto cell dose level will be evaluated by Bayesian piecewise exponential survival regression.



Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years to 70 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Patients with a diagnosis either follicular lymphoma (FL), mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), multiple myeloma (MM), Hodgkin's lymphoma (HL), non-Hodgkin's lymphoma (NHL), chronic myeloid leukemia (CML), myelodysplastic syndrome, myeloproliferative syndromes (MPD), acute myeloid leukemia (AML) or acute lymphoid leukemia (ALL).
  • Patients with aplastic anemia and severe immune deficiency or nonmalignant bone marrow failure states.
  • Patients with hematological malignancies must have had persistent or progressive disease despite initial chemotherapy and must have achieved stable disease or a partial or complete response to their most recent chemotherapy. Patients with low bulk or indolent relapse are eligible without additional treatment. Patients with high risk acute myeloid leukemia by European LeukemiaNet (ELN) criteria in first remission are eligible.
  • Availability of a haploidentical related donor.
  • Karnofsky performance status >= 70%.
  • Left ventricular ejection fraction of at least 40%.
  • Pulmonary function test (PFT) demonstrating an adjusted diffusion capacity of least 50% predicted value for hemoglobin concentration.
  • Serum creatinine =< 1.5 mg/dl.
  • Serum glutamic-pyruvic transaminase (SGPT) =< 200 IU/ml.
  • Bilirubin < 1.5 mg/dl (unless Gilbert's syndrome).
  • Negative pregnancy test in a woman with child bearing potential.

Exclusion Criteria:

  • Human immune deficiency virus (HIV) seropositive.
  • Uncontrolled infection or serious medical or psychiatric condition that would limit tolerance to the protocol treatment.
  • Active central nervous system (CNS) malignancy.
  • Availability of medically eligible, human leukocyte antigen (HLA)-matched related stem cell donor.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03622788


Contacts
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Contact: Richard Champlin 713-792-8750 rchampli@mdanderson.org

Locations
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United States, Texas
M D Anderson Cancer Center Not yet recruiting
Houston, Texas, United States, 77030
Contact: Richard E. Champlin    713-792-8750      
Principal Investigator: Richard E. Champlin         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Richard Champlin M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03622788     History of Changes
Other Study ID Numbers: 2018-0221
NCI-2018-01557 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2018-0221 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: August 9, 2018    Key Record Dates
Last Update Posted: May 21, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No

Additional relevant MeSH terms:
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Lymphoma
Leukemia
Leukemia, Myeloid
Multiple Myeloma
Neoplasms, Plasma Cell
Leukemia, Myeloid, Acute
Lymphoma, Follicular
Myelodysplastic Syndromes
Preleukemia
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphocytic, Chronic, B-Cell
Hodgkin Disease
Lymphoma, Mantle-Cell
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Anemia, Aplastic
Myeloproliferative Disorders
Pancytopenia
Leukemia, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias