AzTrials
AzTrials

Congenital Amegakaryocytic ThrombocytopeniaPhase 2NCT00301834

Alemtuzumab, Fludarabine, and Busulfan Followed By Donor Stem Cell Transplant in Treating Young Patients With Hematologic Disorders

A Phase 2 study testing alemtuzumab, busulfan and cyclosporine in people with Congenital Amegakaryocytic Thrombocytopenia and Diamond-blackfan Anemia, run by University of California, San Francisco at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

RATIONALE: Monoclonal antibodies, such as alemtuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Read more about this study

Who is it for?
Ages Up to 21 years
What is being tested?
alemtuzumab, busulfan and cyclosporine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
35 participants
Where
2 sitesUnited States
Study dates
Jan 2005to Sep 2011
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 Up to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

DISEASE CHARACTERISTICS:

  • Diagnosis of 1 of the following hematologic conditions:
  • Aplastic anemia with marrow aplasia, meeting all of the following criteria:
  • Absolute neutrophil count < 500/mm^3
  • Platelet and/or red cell transfusion dependent
  • Chronic aplastic anemia, meeting all of the following criteria:
  • Transfusion dependent
  • Unresponsive to immunosuppressive therapy
  • Alternative matched unrelated donor has been identified
  • Congenital marrow failure syndrome, including any of the following (with closely matched related or unrelated donor):
  • Primary red cell aplasia (Diamond-Blackfan syndrome)
  • Congenital neutropenia (Kostmann's syndrome)
  • Amegakaryocytic thrombocytopenia
  • Congenital dyserythropoietic anemias
  • Other severe acquired cytopenias in which a transplantation using a combined busulfan/cyclophosphamide conditioning regimen is indicated
  • Hemoglobinopathy (with closely matched related or unrelated donor)
  • β-thalassemia major
  • Sickle cell anemia
  • Hemoglobin E/β-thalassemia
  • Severe immunodeficiency disease
  • Chediak-Higashi disease
  • Wiskott-Aldrich syndrome
  • Combined immunodeficiency disease (Nezelof's)
  • Hyper immunoglobulin M (IgM) syndrome
  • Bare lymphocyte syndrome
  • Chronic granulomatous disease
  • Familial erythrohemophagocytic lymphohistiocytosis
  • Other stem cell defects (e.g., osteopetrosis)
  • Severe immune dysregulation/autoimmune disorders
  • Achieved a transient response to prior immunosuppressive therapy
  • Chronic myelogenous leukemia
  • Disease in first chronic phase
  • Acute myeloid leukemia
  • Disease in first remission
  • Myelodysplastic syndromes
  • Inborn errors of metabolism
  • Histiocytosis
  • No severe combined immunodeficiency disease
  • Matched related or unrelated donor available by high resolution DNA typing
  • Related donor, meeting both of the following criteria:
  • Matched at both human leukocyte antigen (HLA)-Drβ1 alleles
  • No more than 1 mismatch at the 4 HLA-A and -B alleles
  • Unrelated donor, meeting 1 of the following criteria:
  • Marrow matched at both HLA-Drβ1 alleles AND no more than 1 mismatch at the 4 HLA-A and -B alleles
  • Umbilical cord blood matched at 5/6 HLA-A, -B, and -DRβ1 alleles with at least 1 -DRβ1 match AND there are ≥ 3x10^5 CD34+ (Cluster of differentiation 34-positive) cells per kg body weight of recipient available at the time of cryopreservation

PATIENT CHARACTERISTICS:

  • Cardiac ejection fraction ≥ 27%
  • Creatinine clearance ≥ 50 mL/min by 24-hour urine collection or glomerular filtration rate
  • DLCO (diffusion capacity of lung for carbon monoxide) ≥ 50% of predicted (corrected for anemia/lung volume)

PRIOR CONCURRENT THERAPY:

  • No prior transplantation for leukemia from which patient remains engrafted and alemtuzumab is not needed as part of the conditioning regimen

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

    Madison, Wisconsin, 53792-6164

  • UCSF Helen Diller Family Comprehensive Cancer Center

    San Francisco, California, 94115

Other trials in United States

About this study

Official title: Evaluation of Fludarabine, Busulfan and Alemtuzumab as a Reduced Toxicity Ablative Bone Marrow Stem Cell Transplant Regimen for Children With Stem Cell Defects, Marrow Failure Syndromes, or Myelodysplastic Syndrome (MDS)/Leukemia

RATIONALE: Monoclonal antibodies, such as alemtuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as fludarabine and busulfan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. A peripheral stem cell, bone marrow , or umbilical cord blood transplant may be able to replace blood-forming cells that were destroyed by chemotherapy. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine together with methotrexate and methylprednisolone may stop this from happening.

PURPOSE: This phase II trial is studying how well giving alemtuzumab together with fludarabine and busulfan works when given before donor stem cell transplant in treating young patients with hematologic disorders.

Read the detailed description

OBJECTIVES:

Primary

  • Determine the engraftment rate with reduced toxicity ablative conditioning regimen comprising alemtuzumab, fludarabine, and busulfan followed by allogeneic stem cell transplantation in pediatric patients with stem cell defects, marrow failure syndromes, hemoglobinopathy, severe immunodeficiency syndromes (nonsevere combined immunodeficiency disorders), myelodysplastic syndromes, or myeloid leukemia.

Secondary

  • Determine the acute reactions, incidence of infections, and rate of immune reconstitution in patients treated with this regimen.

OUTLINE: This is a multicenter study.

  • Conditioning regimen: Patients receive alemtuzumab IV over 6 hours on days -12 to -10, high-dose busulfan IV over 2 hours 4 times daily on days -9 to -6, and fludarabine IV over 30 minutes on days -5 to -2.
  • Allogeneic stem cell transplantation: Two days after the completion of conditioning regimen, patients undergo allogeneic bone marrow, peripheral blood stem cell, or umbilical cord blood transplantation on day 0. Patients receive filgrastim (G-CSF) subcutaneously beginning on day 5 and continuing until blood counts recover.
  • Graft-vs-host disease (GVHD) prophylaxis:
  • Most transplantations (bone marrow or peripheral blood stem cell transplantation): Patients receive cyclosporine IV continuously beginning on day -1 until at least day 50 followed by a taper at either 2 months, 9 months, or 1 year in the absence of GVHD. Patients also receive methotrexate on days 1, 3, and 6.
  • Umbilical cord blood transplantation: Patients receive cyclosporine as in most transplantations, and methylprednisolone IV twice daily on days 0-21 followed by a weekly taper.

After transplantation, patients are followed periodically for up to 20 years.

PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.

Keywords
de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, childhood acute myeloid leukemia in remission, childhood chronic myelogenous leukemia, congenital amegakaryocytic thrombocytopenia, Diamond-Blackfan anemia, severe congenital neutropenia, secondary acute myeloid leukemia, chronic phase chronic myelogenous leukemia, childhood myelodysplastic syndromes
Medical subject headings
Congenital amegakaryocytic thrombocytopenia, Anemia, Diamond-Blackfan, Leukemia, Myelodysplastic Syndromes, Neutropenia, Severe Congenital, Autosomal Recessive 3, Leukemia, Myeloid, Chronic-Phase

What participants receive

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

Study groups in NCT00301834
Study groupRoleWhat they receive
Single arm - conditioning and transplantExperimentalAlemtuzumab 0.5 mg/kg (maximum 15 mg) daily for 3 days; Busulfan i.v. every 6 hours from day -9 to day -6 for 16 total doses; Fludarabine phosphate from day -5 for 4 days at 1.3 mg/kg (if patient was less than 12 kg) or 40 mg/m*2 per dose; Cyclosporine continuous infusion 3 mg/kg/Day beginning day -1 for GVHD prophylaxis; Methotrexate at 15 mg/m*2 on day +1, 10 mg/m*2 on days +3, +6, and (only for MUDs) day +11 also for GVHD prophylaxis; Methylprednisolone only as required for GVHD prophylaxis; allogeneic bone marrow transplantation or allogeneic hematopoietic stem cell transplantation or peripheral blood stem cell transplantation or umbilical cord blood transplantation.
Receives: Biological: alemtuzumab; Drug: busulfan; Drug: cyclosporine; Drug: fludarabine phosphate; Drug: methotrexate; Drug: methylprednisolone; Procedure: allogeneic bone marrow transplantation; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation; Procedure: umbilical cord blood transplantation

What is being measured

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

  1. Number of Participants Achieving Durable Engraftment (Presence of Donor Cells) at 6 Weeks Post Transplantation

    Peripheral blood chimerism studies were performed by quantitative real time polymerase chain reaction (qPCR) evaluation of differential short tandem repeat DNA sequences

    Measured: 6 weeks post-transplant

Secondary outcomes (4)

  1. Treatment-related Mortality at 100 Days and 1 Year Post Transplantation

    Measured: 100 days and 1 year

  2. Toxicity Grade ≥ 3 From Start of Conditioning Through the First Year Post Transplantation

    Measured: 1 year post-transplantation

  3. Cytomegalovirus (CMV) Viral Infection and Disease Symptoms

    polymerase chain reaction testing for presence of CMV weekly until at least day +100 then every 2 weeks until T-cell reconstitution as defined by cluster of differentiation 4 (CD4) > 200 cells/mm3. Median time to T-cell reconstitution was 6 months.

    Measured: Up to one year post-transplant

  4. Disease-free Survival With Correction of Disease at One Year Post Transplantation

    Patients deemed "alive and well" at follow-up timepoint later than 1-year post-transplantation

    Measured: 1 year post-transplantation

Timeline

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

  1. First posted13 Mar 2006 (estimated)
  2. Study startJan 2005
  3. Primary completionSep 2011
  4. Study completionSep 2011

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
35 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00301834
Sponsor's protocol ID
CDR0000462406
Other IDs
UCSF-04152, UCSF-00452, UCSF-H411-25738-02
Status last verified
Aug 2017
First submitted
9 Mar 2006
Last updated
28 Sep 2017

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing alemtuzumab, busulfan and cyclosporine in people with Congenital Amegakaryocytic Thrombocytopenia and Diamond-blackfan Anemia, run by University of California, San Francisco at 2 sites 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: finished, as of the sponsor's last update on 28 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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 16 May 2013). 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?

Number of Participants Achieving Durable Engraftment (Presence of Donor Cells) at 6 Weeks Post Transplantation (time frame: 6 weeks post-transplant). 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 NCT00301834.

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 28 Sep 2017.

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