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2-Step Approach to Stem Cell Transplant in Treating Participants With Hematological Malignancies

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ClinicalTrials.gov Identifier: NCT03712878
Recruitment Status : Recruiting
First Posted : October 19, 2018
Last Update Posted : February 28, 2019
Sponsor:
Information provided by (Responsible Party):
Thomas Jefferson University ( Sidney Kimmel Cancer Center at Thomas Jefferson University )

Brief Summary:
This phase II trial studies how well a 2-step approach to stem cell transplant works in treating participants with blood cancers. Giving chemotherapy and total body irradiation before a lymphocyte (white blood cell) and stem cell transplant helps stop the growth of cells in the bone marrow including normal blood-forming cells (stem cells) and cancer cells. By giving the donor cells in two steps, the dose of lymphocytes given can be tightly controlled and they can be made more tolerant to the body. When the healthy lymphocytes and 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. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells called graft versus host disease. Giving tacrolimus and mycophenolate mofetil may stop this from happening.

Condition or disease Intervention/treatment Phase
Hematopoietic and Lymphoid Cell Neoplasm Radiation: Total-Body Irradiation Procedure: Donor Lymphocyte Infusion Drug: Cyclophosphamide Procedure: Allogeneic Hematopoietic Stem Cell Transplantation Drug: Tacrolimus Drug: Mycophenolate Mofetil Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To assess whether providing a patient with "5+5" dosing in a 2 step matched related donor hematopoietic stem cell transplantation (HSCT) increases the percentage of patients who achieve full donor chimerism earlier as defined by 98% or greater donor T cell chimerism at 28 days post HSCT (d+28).

SECONDARY OBJECTIVES:

I. To assess day (d) +90 chimerism in patients receiving "5+5" dosing. II. To assess post HSCT relapse rates in patients receiving "5+5" dosing. III. To assess rates of grade II-IV graft versus host disease (GVHD) in patients receiving "5+5" dosing.

IV. To assess treatment-related mortality (TRM) in patients receiving "5+5" dosing.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 34 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A 2 Step Approach to Matched Related Hematopoietic Stem Cell Transplantation for Patients With Hematological Malignancies-5+5 Dosing
Actual Study Start Date : September 19, 2018
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2021

Arm Intervention/treatment
Experimental: Treatment (TBI, DLI, chemotherapy, HSCT, tacrolimus, MMF)

Description CONDITIONING REGIMEN: Participants undergo TBI BID on days -9 to -6.

TRANSPLANT: Participants receive donor lymphocytes IV on day -6 after the last dose of TBI.

CONDITIONING REGIMEN: Participants receive cyclophosphamide IV on days -3 and -2.

TRANSPLANT: Participants undergo hematopoietic stem cell transplantation on day 0.

GVHD PROPHYLAXIS: Participants receive tacrolimus IV beginning on day -1 with taper beginning on day 42 in the absence of GVHD, a suspicion of GVHD, or previous history of GVHD requiring a taper delay. Participants also receive mycophenolate mofetil IV BID beginning on day -1 through day 28 in the absence of GVHD.

Radiation: Total-Body Irradiation
Undergo TBI

Procedure: Donor Lymphocyte Infusion
Given IV

Drug: Cyclophosphamide
Given IV
Other Names:
  • Cycloblastin
  • Cyclophosphamid monohydrate
  • CYCLO-cell

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Undergo HSCT
Other Name: Allogeneic Hematopoietic Cell Transplantation

Drug: Tacrolimus
Given IV

Drug: Mycophenolate Mofetil
Given IV
Other Name: CellCept




Primary Outcome Measures :
  1. Donor T cell chimerism [ Time Frame: At day +28 ]
    For chimerism rates, the method of Atkinson and Brown will be used to allow for the two-stage design. Will be presented with corresponding 95% confidence intervals.


Secondary Outcome Measures :
  1. Donor T cell chimerism [ Time Frame: At day +90 ]
    Will be presented with corresponding 95% confidence intervals. For chimerism rates, the method of Atkinson and Brown will be used to allow for the two-stage design.

  2. Relapse rate [ Time Frame: At 1 year post-hematopoietic stem cell transplantation (HSCT) ]
    Will be presented with corresponding 95% confidence intervals.

  3. Incidence of grades II-IV graft versus host disease (GVHD) [ Time Frame: Within 1 year of HSCT ]
    Will be presented with corresponding 95% confidence intervals.

  4. Rate of treatment-related mortality (TRM) [ Time Frame: At 1 year post-HSCT ]
    Will be presented with corresponding 95% confidence intervals.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Provide signed and dated informed consent form.
  • Have a hematological malignancy or any type of dyscrasia in which allogeneic HSCT is thought to be beneficial.
  • Have a related donor who is no more than a 1-antigen mismatch at the human leukocyte antigen (HLA)-A; B; C; DR loci in the GVHD direction with the patient. (Patients with a syngeneic donor may be treated on this therapeutic approach, but their outcomes will not be part of the statistical aims of the study.
  • LVEF (left ventricular end diastolic function) of >= 45%.
  • DLCO (diffusing capacity of the lung for carbon monoxide) >= 50% of predicted corrected for hemoglobin.
  • FEV-1 (forced expiratory volume at 1 second >= 50% of predicted.
  • Serum bilirubin =< 1.8.
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 x upper limit of normal.
  • Creatinine clearance of >= 60 mL/min.
  • Have a Hematopoietic Cell Transplant Comorbidity Index (HCT-CI) score =< 5 points (patients with greater than 5 points will be allowed for trial with approval of the principal investigator [PI] and at least 1 co-investigator [co-I] not on the primary care team of the patient). This is an adjustment to account for healthy patients who meet the spirit of this protocol but have histories that result in higher than HCT-CI 5 points. An example is a patient with a solid tumor malignancy in their remote history (adds 3 points to HCT-CI total) where the treatment for the malignancy occurred years to decades before and there has been complete recovery of toxicities.
  • Have a Karnofsky performance score (KPS) >= 80%.
  • Women of reproductive potential (defined as women under the age of 50 years still menstruating within 2 months of HSCT despite past history of chemotherapy) will be counseled to use highly effective contraception including oral, intramuscular (IM), or patch contraceptives, intrauterine device (IUD), diaphragm, cervical cap, or contraceptive implant. Pharmacological avoidance of pregnancy and suppression of menstruation may be instituted during the HSCT inpatient stay.
  • Men will be asked to abstain from sexual relations during the treatment period of the HSCT stay.
  • DONOR: All donors are selected and screened for their ability to provide adequate infection-free apheresis products for the patient in a manner that does not put the donor at risk for negative consequences.

Exclusion Criteria:

  • Be human immunodeficiency virus (HIV) positive.
  • Be pregnant or breastfeeding.
  • Have received alemtuzumab or rabbit antithymocyte globulin (ATG) within 8 weeks or horse ATG within 6 weeks of the transplant admission. This exclusion criterion will be documented by the absence of these drugs in the medical record.
  • Patients with evidence of another malignancy, exclusive of a skin cancer that requires only local treatment, should not be enrolled on this protocol without the specific approval of the PI. If the PI disregards this criterion (example of this is localized prostate cancer not yet requiring treatment), the rationale must be documented in the study binder). This exclusion criterion will be documented by the absence of these drugs in the medical record.

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): NCT03712878


Contacts
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Contact: Dolores Grosso, CRNP (215) 955-8874 dolores.grosso@jefferson.edu

Locations
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United States, Pennsylvania
Sidney Kimmel Cancer Center at Thomas Jefferson University Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Dolores Grosso, CRNP    215-955-8874    dolores.grosso@jefferson.edu   
Sponsors and Collaborators
Sidney Kimmel Cancer Center at Thomas Jefferson University
Investigators
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Principal Investigator: Neal Flomenberg, MD Sidney Kimmel Cancer Center at Thomas Jefferson University

Additional Information:
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Responsible Party: Sidney Kimmel Cancer Center at Thomas Jefferson University
ClinicalTrials.gov Identifier: NCT03712878     History of Changes
Other Study ID Numbers: 18D.419
First Posted: October 19, 2018    Key Record Dates
Last Update Posted: February 28, 2019
Last Verified: February 2019

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

Additional relevant MeSH terms:
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Hematologic Neoplasms
Neoplasms by Site
Neoplasms
Hematologic Diseases
Cyclophosphamide
Tacrolimus
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Calcineurin Inhibitors
Enzyme Inhibitors
Antibiotics, Antineoplastic
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents