AzTrials
AzTrials

Sickle Cell DiseasePhase 2NCT00489281

Non-Myeloablative Bone Marrow Transplant for Patients With Sickle Cell Anemia and Other Blood Disorders

A Phase 2 study testing Cyclophosphamide, Fludarabine and Mycophenolate mofetil in people with Sickle Cell Disease, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

RATIONALE: Giving low doses of chemotherapy, such as fludarabine and cyclophosphamide, and total-body irradiation before a donor bone marrow transplant helps stop the growth of abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. Read more about this study

Who is it for?
Ages 2 to 70 yearsHealthy volunteers can take part
Conditions the study is for
Sickle Cell Disease
What is being tested?
Cyclophosphamide, Fludarabine and Mycophenolate mofetil
Could I receive a placebo?
No, everyone receives an active treatment
How many people
43 participants
Where
1 siteUnited States
Study dates
23 Jun 2008to 29 Dec 2018
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 2 to 70 years
  • All sexes
  • Healthy volunteers accepted
  • Child, Adult, Older adult

DISEASE CHARACTERISTICS:

  • Diagnosis of 1 of the following sickle cell anemias (Hb SS):
  • Hb S/β° thalassemia
  • Hb S/β+ thalassemia
  • Hb SC disease
  • Hb SE disease
  • Hb SD disease
  • Hemoglobin SO-Arab disease
  • Hb S/hereditary persistence of fetal hemoglobin
  • Meets 1 of the following criteria:
  • History of invasive pneumococcal disease
  • Stroke or CNS event lasting > 24 hours
  • MRI changes indicative of brain parenchymal damage
  • Evidence of cerebrovascular disease by magnetic resonance angiography
  • Acute chest syndrome requiring exchange transfusion or hospitalization
  • Recurrent vaso-occlusive pain crisis (> 2 per year for the last 2 years)
  • Stage I or II sickle lung disease
  • Sickle retinopathy
  • Osteonecrosis
  • Red cell alloimmunization (> 2 antibodies) during long-term transfusion
  • Constellation of dactylitis in the first year of life AND a baseline hemoglobin < 7 g/dL and leukocytosis (WBC > 13.4/mm^3) in the absence of infection during the second year of life
  • Pitted RBC count > 3.5% during the first year of life
  • Ineligible for or refused bone marrow transplantation from an HLA-matched sibling donor
  • Partially mismatched (at least haploidentical) first-degree relative donor available
  • No minor (donor anti-recipient) ABO incompatibility if an ABO compatible donor is available

PATIENT CHARACTERISTICS:

  • ECOG performance status (PS) 0-1 OR Karnofsky or Lansky PS 70-100%
  • LVEF ≥ 35%
  • FEV_1 and forced vital capacity ≥ 40% predicted
  • Direct bilirubin < 3.1 mg/dL
  • No moderate to severe pulmonary hypertension by ECHO
  • No debilitating medical or psychiatric illness that would preclude study participation
  • No HIV positivity
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

  • No prior transfusions from donor
  • No immunosuppressive agents, including steroids as antiemetics, within 24 hours after the last dose of post-transplantation cyclophosphamide

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    Baltimore, Maryland, 21231-2410

Other trials in United States

About this study

Official title: A Phase II Trial of Non-Myeloablative Conditioning and Transplantation of Partially HLA-Mismatched and HLA-Matched Bone Marrow for Patients With Sickle Cell Anemia and Other Hemoglobinopathies

RATIONALE: Giving low doses of chemotherapy, such as fludarabine and cyclophosphamide, and total-body irradiation before a donor bone marrow transplant helps stop the growth of abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient'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. Giving sirolimus and mycophenolate mofetil after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving fludarabine and cyclophosphamide together with total-body irradiation followed by a donor bone marrow transplant works in treating patients with sickle cell anemia and other blood disorders.

Read the detailed description

OBJECTIVES:

  • Determine the transplant-related mortality and progression-free survival of patients with severe hemoglobinopathies receiving nonmyeloablative conditioning comprising fludarabine phosphate, cyclophosphamide, and total-body irradiation followed by partially HLA-mismatched bone marrow transplantation from first-degree relatives or HLA-matched donors.
  • Characterize donor hematopoietic chimerism at 30, 60, and 180 days after transplantation in these patients.
  • Determine the hematologic and non-hematologic toxicity of this regimen in these patients.

OUTLINE:

  • Preparative regimen: Patients receive fludarabine phosphate IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1-2 hours on days -6 and -5. Patients also undergo total-body irradiation on day -1.
  • Bone marrow transplantation: Patients undergo allogeneic bone marrow transplantation on day 0. Patients then receive cyclophosphamide IV over 1-2 hours on days 3 and 4.
  • Graft-versus-host disease prophylaxis: Patients receive sirolimus orally daily on days 5-365 and oral mycophenolate mofetil 3 times a day on days 5-35.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

Being tested
Cyclophosphamide, Fludarabine, Mycophenolate mofetil, Sirolimus, Allogeneic bone marrow transplant
Keywords
sickle cell disease
Medical subject headings
Anemia, Sickle Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CyclophosphamideDrug

    Also called Cytoxan, Cy, CTX

    Cyclophosphamide (Cy) 14.5 mg/kg/day intravenously (IV) on Days -6 and -5 and 50 mg/kg/day IV on Days +3 and +4.

  • FludarabineDrug

    Also called Fludara

    Fludarabine 30 mg/m^2/day IV on Days -6, -5, -4, -3, and -2.

  • Mycophenolate mofetilDrug

    Also called MMF, CellCept

    Mycophenolate mofetil 15 mg/kg by mouth (PO) three times a day from Day +5 to Day +35.

  • SirolimusDrug

    Also called Rapamune

    The first dose of Sirolimus is 6 mg PO on Day +5. Further dosing is adjusted according to drug levels. Sirolimus is continued through Day +365.

  • Allogeneic bone marrow transplantProcedure or surgery

    Also called Allo BMT

    An allogeneic bone marrow transplant is a procedure that involves taking bone marrow from a donor and giving it to a recipient.

  • Total body irradiation - 200Radiation

    Also called TBI

    200 centigray (cGy) in one fraction on Day -1.

  • LevetiracetamDrug

    Also called Keppra

    Given at 500 mg PO twice daily from Day -6 to Day +365.

  • Anti-thymocyte globulinBiological

    Also called ATG, Thymoglobulin

    Test dose of 0.5 mg/kg IV given on Day -9, then 2 mg/kg/day IV on Day -8 and -7.

  • Total body irradiation - 400Radiation

    Also called TBI

    400 centigray (cGy) in one fraction on Day -1.

Study groups in NCT00489281
Study groupRoleWhat they receive
Transplant - 200 cGyExperimentalConditioning regimen with anti-thymocyte globulin, fludarabine, cyclophosphamide, and total body irradiation - 200. Seizure prophylaxis with levetiracetam. Allogeneic bone marrow transplant infusion on Day 0. Graft-vs-host-disease (GVHD) prophylaxis with cyclophosphamide, mycophenolate mofetil, and sirolimus.
Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Mycophenolate mofetil; Drug: Sirolimus; Procedure: Allogeneic bone marrow transplant; Radiation: Total body irradiation - 200; Drug: Levetiracetam; Biological: Anti-thymocyte globulin
Transplant - 400 cGyExperimentalConditioning regimen with anti-thymocyte globulin, fludarabine, cyclophosphamide, and total body irradiation - 400. Seizure prophylaxis with levetiracetam. Allogeneic bone marrow transplant infusion on Day 0. Graft-vs-host-disease (GVHD) prophylaxis with cyclophosphamide, mycophenolate mofetil, and sirolimus.
Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Mycophenolate mofetil; Drug: Sirolimus; Procedure: Allogeneic bone marrow transplant; Drug: Levetiracetam; Biological: Anti-thymocyte globulin; Radiation: Total body irradiation - 400

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Transplant-related Mortality

    Number of participants who died for reasons related to bone marrow transplant.

    Measured: Up to one year

  2. Progression-free Survival

    Percentage of participants who are alive without relapse.

    Measured: 2 years

Secondary outcomes (2)

  1. Donor Chimerism at 30 Days

    Number of participants with full (95-100%), mixed (5-94%), and no (0-4%) donor cells. Chimerism is reported for unsorted whole blood and T cells.

    Measured: 30 days

  2. Donor Chimerism at 1 Year

    Number of participants with full (95-100%), mixed (5-94%), and no (0-4%) donor cells. Chimerism is reported for unsorted whole blood and T cells.

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jun 2007 (estimated)
  2. Study start23 Jun 2008
  3. Primary completion29 Dec 2018
  4. Study completion29 Dec 2018

Why it stopped: Initiation of CMS BMT study for sickle-cell disease operating under NCT01166009 made further accrual to this study impossible.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
43 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00489281
Sponsor's protocol ID
J0676
Other IDs
P30CA006973, P01CA015396, NA_00002479
Status last verified
Mar 2019
First submitted
20 Jun 2007
Last updated
17 Apr 2019
Individual data sharing
No

Publications

  • Goldenberg M, Varadhan R, Gamper CJ, Cooke KR, Ambinder AJ, Symons HJ, Pecker LH, Jones RJ, Brodsky RA, Bolanos-Meade J. Bone marrow transplantation for sickle cell disease using posttransplantation cyclophosphamide and 400 cGy TBI. Blood Adv. 2026 Apr 14;10(7):2202-2217. doi: 10.1182/bloodadvances.2025017413.

    PubMed 41569644

  • Bolanos-Meade J, Cooke KR, Gamper CJ, Ali SA, Ambinder RF, Borrello IM, Fuchs EJ, Gladstone DE, Gocke CB, Huff CA, Luznik L, Swinnen LJ, Symons HJ, Terezakis SA, Wagner-Johnston N, Jones RJ, Brodsky RA. Effect of increased dose of total body irradiation on graft failure associated with HLA-haploidentical transplantation in patients with severe haemoglobinopathies: a prospective clinical trial. Lancet Haematol. 2019 Apr;6(4):e183-e193. doi: 10.1016/S2352-3026(19)30031-6. Epub 2019 Mar 14.

    PubMed 30878319

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cyclophosphamide, Fludarabine and Mycophenolate mofetil in people with Sickle Cell Disease, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 17 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Transplant-related Mortality (time frame: Up to one year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00489281, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2019.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in