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HemoglobinopathiesPhase 2NCT00034528

Stem Cell Transplantation After Reduced-Dose Chemotherapy for Patients With Sickle Cell Disease or Thalassemia

A Phase 2 study testing Busulfan, Fludarabine and FK506 in people with Hemoglobinopathies and Anemia, Sickle Cell, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

Terminated

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

Official record
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Trial summary

The purpose of this study is to find out if using a lower dose of chemotherapy before stem cell transplantation can cure patients of sickle cell anemia or thalassemia while causing fewer severe side effects than conventional high dose chemotherapy with transplantation. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Busulfan, Fludarabine and FK506
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2 participants
Where
1 siteUnited States
Study dates
Sep 2001to Nov 2003
Phase
Phase 2
Are there results?
None posted in the registry

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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • All patients must:
  • Have related donors who are identical at 6 human leukocyte antigens (HLA) loci (A, B and DR) by molecular typing
  • Have a performance status from 0-2
  • Give written informed consent
  • Patients with sickle cell disease should have 1 or more of the following:
  • Acute chest syndrome requiring recurrent hospitalization or exchange transfusion
Show all 15Show fewer
  • Nonhemorrhagic stroke or central nervous system event lasting longer than 24 hours
  • Recurrent vaso-occlusive pain (2 episodes or more per year) or recurrent priapism
  • Sickle nephropathy (moderate or severe proteinuria or a glomerular filtration rate 30-50 percent of normal predicted value)
  • Bilateral proliferative retinopathy and major visual impairment in at least 1 eye
  • Osteonecrosis of multiple joints
  • Patients with thalassemia should have 1 or more of the following:
  • Transfusion dependence, defined as a transfusion requirement of greater than or equal to 6 units of packed red blood cells over the past 12 months
  • Iron overload, defined as serum ferritin greater than 500 mcg/L in the absence of infection or biopsy-proven iron overload
  • Presence of 2 or more alloantibodies against red cell antigens

Who cannot join

  • Pregnancy
  • Acute hepatitis (transaminases greater than 3 times the normal value)
  • Cardiac ejection fraction less than 30 percent
  • Severe renal impairment (glomerular filtration rate less than 30 percent of predicted normal value)
  • Severe residual functional neurologic impairment (other than hemiplegia alone)
  • Seropositivity for the human immunodeficiency virus (HIV)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Dana-Farber Cancer Institute/Harvard Cancer Center, Brigham and Women's Hospital and Massachusetts General Hospital

    Boston, Massachusetts, 02115

Other trials in United States

About this study

Official title: Allogeneic Stem Cell Transplantation Following Nonmyeloablative Chemotherapy in Patients With Hemoglobinopathies

The purpose of this study is to find out if using a lower dose of chemotherapy before stem cell transplantation can cure patients of sickle cell anemia or thalassemia while causing fewer severe side effects than conventional high dose chemotherapy with transplantation.

Read the detailed description

Hemoglobinopathies, such as sickle cell disease and thalassemia major, are genetic diseases associated with significant morbidity and premature death. Allogeneic bone marrow transplantation (BMT) is the only potential cure for severe hemoglobinopathies. Typical regimens have used high doses of chemotherapy or chemo-radiotherapy to ablate recipient hematopoiesis and to prevent graft rejection. The widespread use of this treatment has been limited by toxicity, risk of end-organ damage, and donor availability. This study will use a nonmyeloablative regimen of fludarabine and busulfan to attempt to generate consistent engraftment with donor hematopoietic stem cells in patients with severe hemoglobinopathy.

G-CSF mobilization of the donor's peripheral blood white blood cells will precede donor apheresis. A nonmyeloablative conditioning regimen of fludarabine and busulfan will be administered to patients prior to allogeneic peripheral blood stem cell infusions. FK506 and prednisone will be administered for graft versus host disease (GVHD) prophylaxis. Patients will be evaluated for engraftment, donor: host hematopoietic chimerism, toxicity, and hemoglobinopathy.

Being tested
Busulfan, Fludarabine, FK506, Prednisone
Medical subject headings
Hemoglobinopathies, Anemia, Sickle Cell, Hemoglobin SC Disease, Thalassemia, beta-Thalassemia

What participants receive

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

  • BusulfanDrug

    Also called Busulfex

    0.8 mg/kg/d administered as a single intravenous infusion over 3 hours for 4 days. All infusions are anticipated to be given in the outpatient clinic.

  • FludarabineDrug

    Also called Fludara, Oforta

    30 mg/m^2/d administered as a bolus infusion over 30 minutes for 4 days. All infusions are anticipated to be given in the outpatient clinic.

  • FK506Drug

    Also called Prograf, Tacromilus

    0.15 mg/kg taken orally daily for 12 to 14 weeks

  • PrednisoneDrug

    0.5 mg/kg taken orally four times daily on Day 7 and increase to 1 mg/kg taken orally four times daily on Day 14. Participants will continue regimen until Day 30 before a 20-25% taper per week.

Study groups in NCT00034528
Study groupRoleWhat they receive
Allogeneic stem cell transplantationExperimentalParticipants will receive a nonmyeloablative conditioning regimen of fludarabine and busulfan prior to allogeneic peripheral blood stem cell (CD34+) infusions. FK506 and prednisone will be administered for graft versus host disease (GVHD) prophylaxis.
Receives: Drug: Busulfan; Drug: Fludarabine; Drug: FK506; Drug: Prednisone

What is being measured

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

  1. Evidence of engraftment of donor hematopoietic cells following administration of low doses of busulfan and fludarabine

    Measured: Throughout study

Secondary outcomes (3)

  1. Solid organ toxicity related to the conditioning regimen

    Measured: Throughout study

  2. Incidence of grade II, III, or IV acute graft versus host disease (GVHD)

    Measured: Throughout study

  3. Level of disease response

    Measured: Throughout study

Timeline

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

  1. First posted1 May 2002 (estimated)
  2. Study startSep 2001
  3. Primary completionNov 2003
  4. Study completionNov 2003

Why it stopped: Due to slow recruitment

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
2 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00034528
Sponsor's protocol ID
DAIT DF/HCC 01-098
Other IDs
P01 A 129530
Status last verified
Apr 2013
First submitted
30 Apr 2002
Last updated
1 May 2013
Results posted
No

Publications

  • Walters MC, Storb R, Patience M, Leisenring W, Taylor T, Sanders JE, Buchanan GE, Rogers ZR, Dinndorf P, Davies SC, Roberts IA, Dickerhoff R, Yeager AM, Hsu L, Kurtzberg J, Ohene-Frempong K, Bunin N, Bernaudin F, Wong WY, Scott JP, Margolis D, Vichinsky E, Wall DA, Wayne AS, Pegelow C, Redding-Lallinger R, Wiley J, Klemperer M, Mentzer WC, Smith FO, Sullivan KM. Impact of bone marrow transplantation for symptomatic sickle cell disease: an interim report. Multicenter investigation of bone marrow transplantation for sickle cell disease. Blood. 2000 Mar 15;95(6):1918-24.

    PubMed 10706855

  • Gomez-Almaguer D, Ruiz-Arguelles GJ, Ruiz-Arguelles A, Gonzalez-Llano O, Cantu OE, Hernandez NE. Hematopoietic stem cell allografts using a non-myeloablative conditioning regimen can be safely performed on an outpatient basis: report of four cases. Bone Marrow Transplant. 2000 Jan;25(2):131-3. doi: 10.1038/sj.bmt.1702100.

    PubMed 10673669

  • Krishnamurti L, Blazar BR, Wagner JE. Bone marrow transplantation without myeloablation for sickle cell disease. N Engl J Med. 2001 Jan 4;344(1):68. doi: 10.1056/NEJM200101043440119. No abstract available.

    PubMed 11187121

  • Andersson BS, Madden T, Tran HT, Hu WW, Blume KG, Chow DS, Champlin RE, Vaughan WP. Acute safety and pharmacokinetics of intravenous busulfan when used with oral busulfan and cyclophosphamide as pretransplantation conditioning therapy: a phase I study. Biol Blood Marrow Transplant. 2000;6(5A):548-54. doi: 10.1016/s1083-8791(00)70064-4.

    PubMed 11071260

  • Wu CJ, Krishnamurti L, Kutok JL, Biernacki M, Rogers S, Zhang W, Antin JH, Ritz J. Evidence for ineffective erythropoiesis in severe sickle cell disease. Blood. 2005 Nov 15;106(10):3639-45. doi: 10.1182/blood-2005-04-1376. Epub 2005 Aug 9.

    PubMed 16091448

  • Wu CJ, Gladwin M, Tisdale J, Hsieh M, Law T, Biernacki M, Rogers S, Wang X, Walters M, Zahrieh D, Antin JH, Ritz J, Krishnamurti L. Mixed haematopoietic chimerism for sickle cell disease prevents intravascular haemolysis. Br J Haematol. 2007 Nov;139(3):504-7. doi: 10.1111/j.1365-2141.2007.06803.x. No abstract available.

    PubMed 17910640

  • Wu CJ, Hochberg EP, Rogers SA, Kutok JL, Biernacki M, Nascimento AF, Marks P, Bridges K, Ritz J. Molecular assessment of erythroid lineage chimerism following nonmyeloablative allogeneic stem cell transplantation. Exp Hematol. 2003 Oct;31(10):924-33. doi: 10.1016/s0301-472x(03)00227-3.

    PubMed 14550808

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Busulfan, Fludarabine and FK506 in people with Hemoglobinopathies and Anemia, Sickle Cell, run by National Institute of Allergy and Infectious Diseases (NIAID) 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?

The sponsor lists 15 inclusion and 6 exclusion criteria. 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 1 May 2013. 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?

The study was stopped early (reason given: Due to slow recruitment). Results are not available in the source record.

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?

Evidence of engraftment of donor hematopoietic cells following administration of low doses of busulfan and fludarabine (time frame: Throughout study). 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 NCT00034528, which also lists 7 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 1 May 2013.

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