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Non-Myeloablative Conditioning and Bone Marrow Transplantation

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2017 by Vanderbilt-Ingram Cancer Center
Information provided by (Responsible Party):
Adetola A. Kassim, Vanderbilt-Ingram Cancer Center Identifier:
First received: May 1, 2013
Last updated: January 9, 2017
Last verified: January 2017
Allogeneic blood or marrow transplantation (alloBMT) is a curative therapy for a variety of hematologic disorders, including sickle cell disease and thalassemia. Even when it is clear that alloBMT can give to these patients an improvement in their disease, myeloablative transplants have important toxicities and mortalities associated. The lack of suitable donors continues to be a limit to access to transplantation. Substantial progress has been made recently in the development of pre-treatment regimens that facilitate the sustained engraftment of donor marrow with reduced toxicity. Most of these regimens incorporate highly immunosuppressive drugs, which allow the reduction or elimination of myeloablative agents or total body irradiation without endangering the sustained engraftment of HLA-identical allogeneic stem cells. Preliminary results of non-myeloablative allogeneic stem cell transplantation suggest that the procedure can be performed in patients who are ineligible for myeloablative alloBMT, and that sustained remissions of several hematologic malignancies can be obtained.

Condition Intervention
Sickle Cell Disease
Drug: Thymoglobulin
Drug: Fludarabine
Drug: Cyclophosphamide (CTX)
Drug: Mesna
Drug: Sirolimus
Drug: Mycophenolate mofetil (MMF)
Procedure: Bone marrow transplantation
Radiation: Total body irradiation

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Non-Myeloablative Conditioning and Transplantation of Partially HLA-Mismatched and HLA-Matched Bone Marrow for Patients With Sickle Cell Disease and Other Hemoglobinopathies

Resource links provided by NLM:

Further study details as provided by Vanderbilt-Ingram Cancer Center:

Primary Outcome Measures:
  • Transplant-related mortality (TRM) [ Time Frame: at 1 year after BMT ]
    Defined as death in the absence of recurrent sickle cell disease or hemoglobinopathy

Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: 2 years ]
    Development of grade II-IV acute graft-vs.-host disease, confirmed histologically by a pathologist.

  • Characterize donor hematopoietic chimerism in peripheral blood after mini-haploBMT [ Time Frame: at days ~30, ~60, and ~180 after mini-haploBMT ]

    Partially human leukocyte antigen (HLA)-mismatched bone marrow from first-degree relatives. Defined in percentages of donor cells in patient's peripheral blood, measured in 4 ways.

    • Mixed donor chimerism: > 0% but < 95%
    • Complete donor chimerism > 95%

    Any amount of donor chimerism after day 60 will be considered as having engrafted

  • Characterize hematologic and non-hematologic toxicities of minihaploBMT [ Time Frame: Day 60 after BMT ]

    Hematologic toxicity:

    -Absolute neutrophil count (ANC): consecutive values of < 500/µL on 3 different days after chemotherapy post-BMT Platelet count: consecutive values of < 20,000 µL on 3 different days after chemotherapy post-BMT

    Non-hematologic toxicities:

    -Toxicities necessitating hospitalization Toxicities grade 4 or above

    Meets the criteria of the following SAE:

    • Relapse of underlying disease
    • Grade 3 ocular toxicity not related to ocular GVHD
    • Grade 3 related non-hematologic toxicity

Estimated Enrollment: 25
Study Start Date: May 2013
Estimated Study Completion Date: November 2017
Estimated Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Non-Myeloablative Conditioning and Bone Marrow Transplantation Drug: Thymoglobulin

Day 9 - 0.5 mg/kg IV before BMT

Days 8 & 7 - 2mg/kg IV before BMT

Drug: Fludarabine
On Days -6 to -2 before BMT, 30 mg/m2/day IV
Other Name: Fludara®
Drug: Cyclophosphamide (CTX)
Days 6 & 5 before BMT, 14.5 mg/kg IV; 50 mg/kg each day on 3rd & 4th day after BMT
Other Name: Cytoxan
Drug: Mesna
Days 3 & 4 after BMT: 40 mg/kg IV
Drug: Sirolimus
Adjusted to maintain a serum trough level of 3-12 ng/mL, taken orally beginning on 5 days after BMT and taken to 1 year after BMT.
Other Name: rapamycin, Rapamune®
Drug: Mycophenolate mofetil (MMF)
15 mg/kg orally with maximum dose 3 mg/day beginning 5 days after BMT and taken to day 35 after BMT
Procedure: Bone marrow transplantation
Day 0 - Transplantation of hematopoietic cells derived from bone marrow of a donor to a recipient as treatment for hematologic disorders
Radiation: Total body irradiation
200 cGy on the day before BMT. Radiation delivered to the entire body of the recipient to eradicate bone marrow cells in the recipient to prepare the recipient to receive the transplanted


Ages Eligible for Study:   2 Years to 70 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

Patients who are ineligible for BMT from an HLA-matched sibling donor can proceed to a haplo-BMT. Patients with an HLA-matched related donor will proceed to a matched BMT.

  • Age 2-70 years
  • Good performance status (ECOG 0 or 1; Karnofsky and Lansky 70-100)
  • Patients and donors must be able to sign consent forms. First degree relative should be willing to donate
  • Patients must be geographically accessible and willing to participate in all stages of treatment.
  • Eligible diagnoses: Patients with sickle cell anemia such as sickle cell anemia (Hb SS), Hb Sβ° thalassemia, Hb Sβ+ thalassemia, Hb SC disease, Hb SE disease, Hb SD disease, Hemoglobin SO- Arab disease HbS with hereditary persistence of fetal hemoglobin. Other significant hemoglobinopathies that also fulfill criterion from below.

Plus one of the following:

  1. Stroke or central nervous system event lasting more than 24 hours.
  2. MRI changes indicative of brain parenchyma damage.
  3. MRA evidence of cerebrovascular disease.
  4. Acute chest syndrome requiring exchange transfusion or hospitalization.
  5. Recurrent vaso-occlusive pain episodes and hospitalization crisis (more than 2/year for the last 2 years).
  6. Stage I or II sickle lung disease.
  7. Transfusion dependent thalassemia

Exclusion Criteria:

Poor performance status (ECOG>1).

  • Poor cardiac function: left ventricular ejection fraction<35%.
  • Poor pulmonary function: FEV1 and FVC<40% predicted.
  • Pulmonary hypertension moderate to severe by echocardiographic standards.
  • Poor liver function: direct bilirubin >3.1 mg/dl
  • HIV-positive
  • Minor (donor anti-recipient) ABO incompatibility if an ABO compatible donor is available.
  • Prior transfusions from donor or recipient if caused alloimmunization vs. donor cells.
  • Women of childbearing potential who currently are pregnant (Beta-HCG+) or who are not practicing adequate contraception.
  • Patients who have any debilitating medical or psychiatric illness that would preclude their giving informed consent or their receiving optimal treatment and follow-up.

Criteria for donor eligibility

  • Weight ≥ 20kg and age ≥ 18 years
  • Donors must meet the selection criteria as defined by the Foundation for the Accreditation of Hematopoietic Cell Therapy (FAHCT) and will be screened per the American Association of Blood Banks (AABB). (AABB guidelines and the recipients will be informed of any deviations.)
  • When more than one donor is available, the donor with the lowest number of HLA allele mismatches will be chosen, unless there is HLA cross-match incompatibility or a medical reason to select otherwise, in which case donor selection is the responsibility of the PI, in consultation with the immunogenetics laboratory. In cases where there is more than one donor with the least degree of mismatch,donors will be selected based on the most favorable combination of (i) HLA compatibility in cross-match testing and (ii) ABO compatibility:
  • HLA crossmatching (in order of priority)

    1. Mutually compatible (no cross-matching antibodies)
    2. Recipient non-cross-reactive with donor, donor cross-reactive with recipient
    3. Mutually cross-reactive
  • ABO compatibility (in order of priority)

    • Compatible
    • Major incompatibility
    • Minor incompatibility
    • Major and minor incompatibility
  • Donors will be selected to minimize HLA mismatch in the host-versus-graft direction.
  • Donor must have a hemoglobin S =/< ~50%.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01850108

Contact: Vanderbilt-Ingram Clinical Trials Information Program 800-811-8480

United States, Tennessee
Vanderbilt-Ingram Cancer Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Clinical Trials Information Program    800-811-8480      
Principal Investigator: Adetola A Kassim, MD         
Sponsors and Collaborators
Vanderbilt-Ingram Cancer Center
Principal Investigator: Adetola A Kassim, MD Vanderbilt-Ingram Cancer Center
  More Information

Additional Information:
Responsible Party: Adetola A. Kassim, Associate Professor of Medicine; Clinical Director, Sickle Cell Anemia Program; Medical Oncologist, Vanderbilt-Ingram Cancer Center Identifier: NCT01850108     History of Changes
Other Study ID Numbers: VICCNC BMT 12108
Study First Received: May 1, 2013
Last Updated: January 9, 2017

Additional relevant MeSH terms:
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Hematologic Diseases
Genetic Diseases, Inborn
Mycophenolate mofetil
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
Enzyme Inhibitors
Antibiotics, Antineoplastic
Anti-Bacterial Agents
Anti-Infective Agents
Antifungal Agents processed this record on April 21, 2017