Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

URMC Related Haplo-identical Donor BMT (HaploOnly)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02660281
Recruitment Status : Recruiting
First Posted : January 21, 2016
Last Update Posted : August 19, 2019
Sponsor:
Information provided by (Responsible Party):
Jeffrey Andolina, University of Rochester

Brief Summary:
This study will be a single-center treatment protocol, designed to validate the process of related donor haploidentical-SCT at the Wilmot Cancer Institute Blood and Marrow Transplant Unit.

Condition or disease Intervention/treatment Phase
Hematological Disease Immune Deficiencies Solid Tumors Myelofibrosis Multiple Myeloma Lymphoma Radiation: Total Body Irradiation 1200 cGy Drug: Fludarabine Drug: Pre-Stem Cell Infusion Cyclophosphamide Drug: Pre-Stem Cell Infusion Mesna Drug: Busulfan Drug: Melphalan Procedure: Stem Cell Infusion Drug: Post-Stem Cell Infusion Cyclophosphamide Drug: Post-Stem Cell Infusion Mesna Drug: Thiotepa Phase 1

Detailed Description:
This study will be a single-center treatment protocol with five possible preparative regimens, designed to validate the process of related donor haploidentical-SCT at the Wilmot Cancer Institute Blood and Marrow Transplant Unit. Enrolled patients will receive chemotherapy +/- radiation as a pre-transplant conditioning regimen. Patients will then receive haploidentical stem cells, either bone marrow or mobilized peripheral blood, followed by GvHD prophylaxis that will include cyclophosphamide. Multiple data points will be collected prior to, during, and following transplantation to ensure safety of the process and to evaluate the stated objectives.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Haploidentical Donor Hematopoietic Stem Cell Transplantation
Study Start Date : October 2015
Estimated Primary Completion Date : October 2025
Estimated Study Completion Date : October 2026


Arm Intervention/treatment
Full Intensity TBI-based Conditioning
Total Body Irradiation 1200 cGy of 150 cGy over 4 or 5 days, days -5 or -4 to -1 Fludarabine 30 mg/m2/day x 3 days, days -6, -5, -4 Stem Cell Infusion, day 0 Post- Stem Cell Infusion Cyclophosphamide 50 mg/kg/day x 2 days, days +3 and +4 Mesna 50 mg/kg/day x 2 days, days +3 and +4
Radiation: Total Body Irradiation 1200 cGy
1200 cGy TBI in 8 fractions
Other Name: TBI

Drug: Fludarabine
Fludarabine

Procedure: Stem Cell Infusion
Stem cell infusion

Drug: Post-Stem Cell Infusion Cyclophosphamide
Cyclophosphamide given after the stem cell infusion

Drug: Post-Stem Cell Infusion Mesna
Mesna given after the Stem Cell Infusion

Full Intensity Chemo-Only Conditioning
Fludarabine 25 mg/m2/day x 5 days, days -6, -5, -4, -3, -2 Busulfan 130 mg/m2/day x 4 days, days -6, -5, -4, -3 Pre-Stem Cell Infusion Cyclophosphamide 14.5 mg/kg/day x 2 days, days -3 and -2 Pre-Stem Cell Infusion Mesna 14.5 mg/kg/day x 2 days, days -3 and -2 Stem Cell Infusion, day 0 Post-Stem Cell Infusion Cyclophosphamide 50 mg/kg/day x 2 days, days +3 and +4 Post-Stem Cell Infusion Mesna 50 mg/kg/day x 2 days, days +3 and +4
Drug: Fludarabine
Fludarabine

Drug: Pre-Stem Cell Infusion Cyclophosphamide
Cyclophosphamide given prior to the stem cell infusion

Drug: Pre-Stem Cell Infusion Mesna
Mesna given prior to the stem cell infusion

Drug: Busulfan
Busulfan

Procedure: Stem Cell Infusion
Stem cell infusion

Drug: Post-Stem Cell Infusion Cyclophosphamide
Cyclophosphamide given after the stem cell infusion

Drug: Post-Stem Cell Infusion Mesna
Mesna given after the Stem Cell Infusion

Reduced Intensity Conditioning
Fludarabine 30 mg/m2/day x 5 days, days -6 to -2 Melphalan 140 mg/m2/day x 1 day, day -2 Stem Cell Infusion, day 0 Post-Stem Cell Infusion Cyclophosphamide 50 mg/kg/day x 2 days, days +3 and +4 Post-Stem Cell InfusionMesna 50 mg/kg/day x 2 days, days +3 and +4
Drug: Fludarabine
Fludarabine

Drug: Melphalan
Melphalan

Procedure: Stem Cell Infusion
Stem cell infusion

Drug: Post-Stem Cell Infusion Cyclophosphamide
Cyclophosphamide given after the stem cell infusion

Drug: Post-Stem Cell Infusion Mesna
Mesna given after the Stem Cell Infusion

Non-Myeloablative Conditioning
Fludarabine 30 mg/m2/day x 5 days, days -6 to -2 Pre-Stem Cell Infusion Cyclophosphamide 14.5 mg/kg/day x 2 days, days -3 and -2 Pre-Stem Cell InfusionMesna 14.5 mg/kg/day x 2 days, days -3 and -2 Total Body Irradiation 200 cGy, day -1 Stem Cell Infusion, day 0 Post-Stem Cell Infusion Cyclophosphamide 50 mg/kg/day x 2 days, day +3 and +4 Post-Stem Cell Infusion Mesna 50 mg/kg/day x 2 days, day +3 and +4
Radiation: Total Body Irradiation 1200 cGy
1200 cGy TBI in 8 fractions
Other Name: TBI

Drug: Fludarabine
Fludarabine

Drug: Pre-Stem Cell Infusion Cyclophosphamide
Cyclophosphamide given prior to the stem cell infusion

Drug: Pre-Stem Cell Infusion Mesna
Mesna given prior to the stem cell infusion

Procedure: Stem Cell Infusion
Stem cell infusion

Drug: Post-Stem Cell Infusion Cyclophosphamide
Cyclophosphamide given after the stem cell infusion

Drug: Post-Stem Cell Infusion Mesna
Mesna given after the Stem Cell Infusion

Reduced Intensity Conditioning with Addition of Thiotepa
Fludarabine 30 mg/m2/day x 5 days, days -6 to -2 Thiotepa 8 mg/kg, day -3 Melphalan 140 mg/m2/day x 1 day, day -2 Stem Cell Infusion, day 0 Post-Stem Cell Infusion Cyclophosphamide 50 mg/kg/day x 2 days, days +3 and +4 Post-Stem Cell InfusionMesna 50 mg/kg/day x 2 days, days +3 and +4
Drug: Fludarabine
Fludarabine

Drug: Melphalan
Melphalan

Procedure: Stem Cell Infusion
Stem cell infusion

Drug: Post-Stem Cell Infusion Cyclophosphamide
Cyclophosphamide given after the stem cell infusion

Drug: Post-Stem Cell Infusion Mesna
Mesna given after the Stem Cell Infusion

Drug: Thiotepa
Thiotepa




Primary Outcome Measures :
  1. The number of days from the date of the stem cell infusion to engraftment of absolute neutrophils (ANC) and platelets (PLT) will be determined based on daily CBC and differential counts. [ Time Frame: 42 days following the infusion of stem cells for ANC. [If engraftment of ANC does not occur within 42 days, a subsequent transplant will be performed if a donor is available. ]
    The date of engraftment of ANC is the first of 3 consecutive days of ANC of 500 or higher. The date of engraftment of platelets is the first of 3 consecutive days of platelet counts of 20,000 or higher in the absence of platelet transfusions for at least 7 days prior.

  2. Rate of non-engraftment and secondary graft failure [ Time Frame: At 100 days, 6 months, and yearly after transplant from the date of transplant until the date of documented graft failure or the subject's date of death up to 120 months. ]
    The percentage of patients who fail to engraft ANC will be tabulated as well as the percentage of patients who have primary engraftment of ANC but whose graft then fails as evidenced by pancytopenia and failure of bone marrow function.


Secondary Outcome Measures :
  1. Percentage of subjects who develop acute graft-versus-host disease. [ Time Frame: 100 days following the infusion of stem cells ]
    Assess the presence and date of onset of acute GvHD based on the criteria published by Przepiorka et al., Bone Marrow Transplant 1995; 15(6):825-8 as used by the Center for International Blood & Marrow Transplant Research.

  2. Assess the Maximum Overall Grades 0- IV of acute GvHD and Maximum Severity (0-4) by involved organ system in patients who develop acute graft-versus-host disease. [ Time Frame: 100 days following the infusion of stem cells ]
    Assess the severity of acute GvHD based on the criteria published by Przepiorka et al., Bone Marrow Transplant 1995; 15(6):825-8 as used by the Center for International Blood & Marrow Transplant Research.

  3. Percentage of subjects who develop chronic graft-versus-host disease. [ Time Frame: Minimally at intervals of 100 days, 6 months and then yearly following the infusion of stem cells until the subject's date of death.or up to 120 months. ]
    Calculate the percentage of patients who develop chronic graft-versus-host disease based on Sullivan KM, Blood 1981; 57:267 as used by the Center for International Blood & Marrow Transplant Research.

  4. Assess the Maximum Grade: Limited versus Extensive; Maximum Severity: Mild, Moderate or Severe) of chronic GvHD in patients who develop chronic graft-versus- [ Time Frame: Minimally at intervals of 100 days, 6 months and then yearly following the infusion of stem cells until the subject's date of death or up to 120 months. ]
    Assess the severity of chronic GvHD in patients who develop chronic graft-versus-host disease based on Sullivan KM, Blood 1981; 57:267 as used by the Center for International Blood & Marrow Transplant Research.

  5. Disease-free survival [ Time Frame: Disease assessments are performed and reported at time points that include 100 days, 6 months, and yearly until documented progression of disease or the date of death or up to 120 months. ]
    Document and update the length of time a subject survives without recurrence of the disease for which they were transplanted minimally at 100 days. 6 months, and yearly following the infusion of stem cells for as long as the patient survives and remains disease-free.

  6. Time to relapsed disease [ Time Frame: Disease assessments are performed and reported at time points that include 100 days, 6 months, and yearly until the date of documented progression or the subject's date of death or up to 120 months. ]
    Document the time to relapse of the disease for which the patient was Minimally assessments will be performed at 100 days. 6 months, and yearly following the infusion of stem cells for as long as the patient survives and remains disease-free.

  7. Immune reconstitution [ Time Frame: At 100 day, 6 month and one year intervals following the infusion of stem cells until the subject's date of death or up to 120 months. ]
    Evaluate immune reconstitution by measurement of immunoglobulins (IgG, IgA, and IgM), assessment of infections, and lymphocyte analysis



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   6 Months to 75 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patient Age:

  • Pediatric (ages 6 months to 18 years)
  • Adult (ages 18-75 years)

Disease:

Congenital and Other Non-malignant Disorders

  • Immunodeficiency disorders (e.g. Severe Combined Immunodeficiency, Wiskott-Aldrich Syndrome)
  • Congenital hematopoietic stem cell defects (e.g. Chediak-Higashi Syndrome, Congenital Osteopetrosis, Osteogenesis Imperfecta)
  • Metabolic disorders (e.g. Hurler's Syndrome)
  • Hemoglobinopathies (e.g. Sickle Cell Disease, Thalassemia)
  • Severe aplastic anemia

High-Risk Leukemias

Acute Myelogenous Leukemia

  • Refractory to standard induction therapy (more than 1 cycle required to achieve remission)
  • Recurrent (in CR≥2)
  • Treatment-related AML or MDS
  • Evolved from myelodysplastic syndrome
  • Presence of Flt3 abnormalities
  • FAB M6 or M7
  • Adverse cytogenetics

Myelodysplastic Syndrome

Acute Lymphoblastic Leukemia including T lymphoblastic leukemia

  • Refractory to standard induction therapy (time to CR >4 weeks)
  • Recurrent (in CR ≥2)
  • WBC count >30,000/mcL at diagnosis
  • Age >30 at diagnosis
  • Adverse cytogenetics, such as (t(9:22), t(1:19), t(4:11), other MLL rearrangements.

Chronic Myelogenous Leukemia in accelerated phase or blast crisis

Biphenotypic or undifferentiated leukemia

Burkitt's leukemia or lymphoma

Lymphoma:

  • Large cell, Mantle cell, Hodgkin lymphoma refractory or recurrent, chemosensitive, and ineligible for an autologous stem cell transplant or previously treated with autologous SCT
  • Marginal zone or follicular lymphoma that is progressive after at least two prior therapies

Multiple Myeloma, recurrent following high-dose therapy and autologous SCT or ineligible for an autologous HSCT

Solid tumors, with efficacy of allogeneic HSCT demonstrated for the specific disease and disease status

Graft failure following prior related donor, unrelated donor or UCB transplant

Myelofibrosis

Exclusion Criteria:

  1. Patient Age below 6 months or over 75 years
  2. Availability of a 10/10 HLA-matched related or unrelated donor within a reasonable time-frame dictated by the clinical urgency of the transplant
  3. Autologous HSCT < 6 months prior to proposed haplo-SCT
  4. Pregnant or breast-feeding
  5. Current uncontrolled infection
  6. Evidence of HIV infection or positive HIV serology
  7. Anti-donor HLA antibodies with positive crossmatch and unsuccessful -

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): NCT02660281


Contacts
Layout table for location contacts
Contact: Jeffrey Andolina, MD 585-275-2981 jeffrey_andolina@urmc.rochester.edu
Contact: Jessica Mavor 585-275-9680 jessica_mavor@urmc.rochester.edu

Locations
Layout table for location information
United States, New York
Wilmot Cancer Institute Recruiting
Rochester, New York, United States, 14642
Contact: Jeffrey Andolina, MD    585-275-2981    jeffrey_andolina@urmc.rochester.edu   
Contact: Jessica Mavor    585-275-9680    jessica_mavor@urmc.rochester.edu   
Sponsors and Collaborators
University of Rochester
Investigators
Layout table for investigator information
Principal Investigator: Jeffrey Andolina, MD Wilmot Cancer Center
Layout table for additonal information
Responsible Party: Jeffrey Andolina, Medical Director, Pediatric BMT, University of Rochester
ClinicalTrials.gov Identifier: NCT02660281    
Other Study ID Numbers: UBMT 15056
First Posted: January 21, 2016    Key Record Dates
Last Update Posted: August 19, 2019
Last Verified: August 2019
Additional relevant MeSH terms:
Layout table for MeSH terms
Multiple Myeloma
Primary Myelofibrosis
Hematologic Diseases
Immunologic Deficiency Syndromes
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Myeloproliferative Disorders
Bone Marrow Diseases
Cyclophosphamide
Melphalan
Busulfan
Thiotepa
Fludarabine
Mesna
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents