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Non-Myeloablative Conditioning and Bone Marrow Transplantation

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. Read our disclaimer for details. Identifier: NCT01850108
Recruitment Status : Active, not recruiting
First Posted : May 9, 2013
Last Update Posted : January 5, 2023
Information provided by (Responsible Party):
Adetola A. Kassim, Vanderbilt-Ingram Cancer Center

Brief Summary:
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 or disease Intervention/treatment Phase
Sickle Cell Disease Hemoglobinopathies Drug: Thymoglobulin Drug: Fludarabine Drug: Cyclophosphamide (CTX) Drug: Mesna Drug: Sirolimus Drug: Mycophenolate mofetil (MMF) Procedure: Bone marrow transplantation Radiation: Total body irradiation Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 21 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : May 2013
Estimated Primary Completion Date : September 2023
Estimated Study Completion Date : March 2024

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. 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 :
  1. Progression-free survival [ Time Frame: 2 years ]
    Development of grade II-IV acute graft-vs.-host disease, confirmed histologically by a pathologist.

  2. Characterize donor hematopoietic chimerism in peripheral blood after mini-haploBMT [ Time Frame: at days ~30, ~60, ~100 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

  3. 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

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 70 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes


  • 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 1-70 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.

Plus one of the following:

  • Attenuation of progressive disease (adults):
  • Severe and debilitating vaso-occlusive pain despite hydroxyurea or regular blood transfusion therapy.
  • Stroke and silent infarct; stroke or central nervous system event lasting more than 24 hours; MRI changes indicative of brain parenchyma damage and MRA evidence of cerebrovascular disease.
  • Recurrent acute chest syndrome requiring exchange hospitalization.
  • Chronic lung disease as defined by progressive restrictive disease irrespective of oxygen requirements.
  • Chronic kidney disease, CKD stage II - IV
  • Transfusion dépendent thalassemia


  • 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. However, patients with history of stroke and significant cognitive deficit,that would preclude giving informed consent or assent will not be excluded, if they have a family member or significant other with Power of Attorney to also consent of their behalf.


  • Weight ≥ 20kg and age ≥ 18 years or per institutional guidelines
  • 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.)
  • HLA-haploidentical first-degree relatives of the patient. Participants must be HLA typed at high resolution using DNA based typing at HLA-A, -B, -C and DRB1 and have available: An HLA haploidentical first degree relative donor (parents, siblings or half siblings, or children) with 2, 3, or 4 (out of 8) HLA-mismatches who is willing and able to donate bone marrow. A unidirectional mismatch in either the graft versus host or host versus graft direction is considered a mismatch. The donor and recipient must be HLA identical for at least one antigen (using high resolution DNA based typing) at the following genetic loci: HLA-A, HLA-B, HLA-C, and HLA-DRB1. Fulfillment of this criterion shall be considered sufficient evidence that the donor and recipient share one HLA haplotype, and typing of additional family members is not required.

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:

  • HLA compatibility in cross-match testing and
  • ABO compatibility
  • Donor age <40 years
  • Avoid female donors for male recipients and
  • Avoid CMV mismatched donor-recipient transplants:

HLA cross-matching (in order of priority):

  • Mutually compatible (no cross-matching antibodies)
  • Recipient non-cross-reactive with donor, donor cross-reactive with recipient
  • 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.
  • Donors fulfilling the following criteria are ineligible for registration onto this study:
  • All donors will be screened by hemoglobin electrophoresis; donors with a clinically significant hemoglobinopathy are ineligible. Sickle trait is acceptable.

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 identifier (NCT number): NCT01850108

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United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt-Ingram Cancer Center
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Principal Investigator: Adetola A Kassim, MD Vanderbilt-Ingram Cancer Center
Additional Information:
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Responsible Party: Adetola A. Kassim, Associate Professor of Medicine; Clinical Director, Sickle Cell Anemia Program; Medical Oncologist, Vanderbilt-Ingram Cancer Center Identifier: NCT01850108    
Other Study ID Numbers: VICCNCCTT12108
First Posted: May 9, 2013    Key Record Dates
Last Update Posted: January 5, 2023
Last Verified: January 2023
Additional relevant MeSH terms:
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Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Hematologic Diseases
Genetic Diseases, Inborn
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
Antibiotics, Antineoplastic
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Enzyme Inhibitors
Antifungal Agents