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Acute Myeloid Leukemia in RemissionPhase 2NCT00453388

Fludarabine Phosphate, Cyclophosphamide, and Total-Body Irradiation Followed by Donor Bone Marrow Transplant, Mycophenolate Mofetil, and Cyclosporine in Treating Patients With Fanconi Anemia

A Phase 2 study testing Allogeneic Bone Marrow Transplantation, Cyclophosphamide and Cyclosporine in people with Acute Myeloid Leukemia in Remission and de Novo Myelodysplastic Syndrome, run by Fred Hutchinson Cancer Center at 5 sites in 2 countries.

Completed

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

Official record
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Trial summary

This phase II trial studies how well total-body irradiation (TBI) works when given together with fludarabine phosphate and cyclophosphamide followed by donor bone marrow transplant, mycophenolate mofetil, and cyclosporine in treating patients with Fanconi anemia (FA). Read more about this study

Who is it for?
Any age
What is being tested?
Allogeneic Bone Marrow Transplantation, Cyclophosphamide and Cyclosporine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
5 sitesin 2 countries
Study dates
Feb 2007to Jun 2013
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 Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Any patient with FA and bone marrow (BM) failure involving 2 of the following 3 lineages: granulocyte count < 0.5 x 10^9/L, platelet count < 20 x 10^9/L, or hemoglobin < 8 g/dL
  • Any patient with FA who requires red blood cell or platelet transfusions because of marrow failure
  • Any patient with FA who has a life-threatening BM failure involving a single hematopoietic lineage
  • Any patient with FA and pre-existing cytogenetic abnormality including hematopoietic malignancy (acute myeloid leukemia [AML] or myelodysplastic syndrome [MDS]) in morphological remission (defined as absence of circulating blasts and bone marrow blasts < 5% as assessed by morphology); Note that hematopoietic recovery is not required for remission status
  • Patients must have a negative cytotoxic cross match with donor
  • DONOR: Related, human leukocyte antigen (HLA)-haploidentical donors must be identical for one HLA haplotype and mismatched for any number of HLA-A, -B, -C, DRB1 or DQB1 loci of the unshared haplotype
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  • DONOR: Unrelated, HLA-matched donors must be matched at HLA-A, B, C, DRB1 and DQB1 by deoxyribonucleic acid (DNA) typing at the highest resolution routinely available at the time of donor selection; a single allele mismatch at HLA-A, B, or C is allowed OR a single DQB1 mismatch is allowed
  • DONOR: Bone marrow will be the only allowed hematopoietic stem cell source
  • DONOR: Haploidentical donor selection will be based on standard institutional criteria, otherwise no specific prioritization will be made amongst the suitable available donors

Who cannot join

  • Patients having available HLA-matched related donors
  • Significant organ dysfunction that would prevent compliance with conditioning, graft-versus-host disease (GVHD) prophylaxis, or would severely limit the probability of survival, such as liver disease/failure (active hepatitis, moderate to severe portal fibrosis/cirrhosis confirmed by biopsy or uncorrectable hepatic synthetic dysfunction), lung disease, or cardiac disease (ejection fraction < 35%, or if unable to obtain ejection fraction, shortening fraction of < 26%; if shortening is < 26% a cardiology consult is required with principal investigator [PI] having final approval of eligibility)
  • Human immunodeficiency virus (HIV) seropositive patients
  • Fertile females who are unwilling to use contraceptive techniques during and for the twelve months following treatment, as well as females who are pregnant or actively breast feeding
  • Fertile males who are unwilling to use contraceptive techniques during and for the twelve months following treatment
  • AML/MDS in morphological relapse, defined as having circulating blasts or bone marrow blasts >= 5% as assessed by morphology
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  • Active infectious disease concerns
  • Karnofsky performance score < 50 or Lansky performance score < 40
  • DONOR: Donors found to have Fanconi anemia based on chromosomal breakage analysis
  • DONOR: Donors who are not expected to meet the minimum target dose of marrow cells (1 x 10^8 nucleated cells/kg recipient ideal body weight [IBW]) or who are unwilling to be bone marrow donors
  • DONOR: HIV-positive donors
  • DONOR: Donors who are cross-match positive with recipient
  • DONOR: Recipient homozygous at mismatched locus; if the recipient is homozygous at HLA-A, B, or C and the donor is mismatched at that locus, the donor should be avoided; exceptions must be discussed with the PI

Trial locations and contacts

5 sites in 2 countries.

5 sites in 2 countries

United States4 sites

  • Children's Hospital of Wisconsin

    Milwaukee, Wisconsin, 53201

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Children's Hospital and Research Center at Oakland

    Oakland, California, 94609-1809

  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

Brazil1 site

  • Universidade Federal do Paraná

    Curitiba, Paraná, 80060-000

Other trials in Brazil

About this study

Official title: Nonmyeloablative Hematopoietic Cell Transplantation for Patients With Fanconi Anemia Using Alternative Marrow Donors: A Phase II Dose-Finding Study

This phase II trial studies how well total-body irradiation (TBI) works when given together with fludarabine phosphate and cyclophosphamide followed by donor bone marrow transplant, mycophenolate mofetil, and cyclosporine in treating patients with Fanconi anemia (FA). Giving low doses of chemotherapy, such as fludarabine phosphate and cyclophosphamide, and TBI before or after a donor bone marrow transplant helps stop the growth of abnormal cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving mycophenolate mofetil and cyclosporine after the transplant may stop this from happening.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Identify doses of total-body irradiation (TBI) that lead to sufficient probability of donor engraftment (> 5% donor cluster of differentiation [CD]3 chimerism) by day +200.

II. Evaluate the probability of severe acute graft-versus-host disease.

SECONDARY OBJECTIVES:

  1. Evaluate the probabilities of overall survival, regimen-related toxicity (RRT), and recurrent hematopoietic malignancy in those patients with a prior underlying history of such.

II. Examine the degree to which mixed chimerism provides for amelioration of symptoms (i.e., infections due to neutropenia, hemorrhage due to thrombocytopenia) associated with bone marrow failure.

III. Determine if the FA complementation group and % initial mosaicism predict engraftment and RRT outcomes.

OUTLINE: Patients are assigned to 1 of 4 treatment arms.

NOTE: Patients no longer receive pre-transplant cyclophosphamide as of February 2009.

After completion of study treatment, patients are followed up at 6 months and then annually thereafter.

Being tested
Allogeneic Bone Marrow Transplantation, Cyclophosphamide, Cyclosporine, Fludarabine Phosphate, Laboratory Biomarker Analysis
Medical subject headings
Fanconi Anemia

What participants receive

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

  • Allogeneic Bone Marrow TransplantationProcedure or surgery

    Also called Allo BMT, Allogeneic BMT

    Undergo allogeneic bone marrow transplant

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • CyclosporineDrug

    Also called 27-400, Ciclosporin, CsA, Cyclosporin

    Given IV or PO

  • Fludarabine PhosphateDrug

    Also called 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Mycophenolate MofetilDrug

    Also called Cellcept, MMF

    Given PO

  • Nonmyeloablative Allogeneic Hematopoietic Stem Cell TransplantationProcedure or surgery

    Also called Non-myeloablative allogeneic transplant, Nonmyeloablative Stem Cell Transplantation, NST

    Undergo allogeneic stem cell transplant

  • Total-Body IrradiationRadiation

    Also called TOTAL BODY IRRADIATION, Whole-Body Irradiation

    Undergo TBI

Study groups in NCT00453388
Study groupRoleWhat they receive
Arm I (2 vs 2.5 vs 3 Gy TBI dose-escalation)ExperimentalPatients with a history of hematologic malignancy and HLA-haploidentical donor receive fludarabine phosphate (FLU) intravenously (IV) over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF orally (PO) thrice daily (TID) on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD.
Receives: Procedure: Allogeneic Bone Marrow Transplantation; Drug: Cyclophosphamide; Drug: Cyclosporine; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Drug: Mycophenolate Mofetil; Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation; Radiation: Total-Body Irradiation
Arm II (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI de-escalation)ExperimentalPatients with no history of hematological malignancy and HLA-haploidentical donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD.
Receives: Procedure: Allogeneic Bone Marrow Transplantation; Drug: Cyclophosphamide; Drug: Cyclosporine; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Drug: Mycophenolate Mofetil; Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation; Radiation: Total-Body Irradiation
Arm III (2 vs 2.5 vs 3 Gy TBI dose-escalation)ExperimentalPatients with history of hematologic malignancy and HLA-matched unrelated donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD.
Receives: Procedure: Allogeneic Bone Marrow Transplantation; Drug: Cyclophosphamide; Drug: Cyclosporine; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Drug: Mycophenolate Mofetil; Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation; Radiation: Total-Body Irradiation
Arm IV (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI de-escalation)ExperimentalPatients with no history of hematological malignancy and HLA-matched unrelated donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD.
Receives: Procedure: Allogeneic Bone Marrow Transplantation; Drug: Cyclophosphamide; Drug: Cyclosporine; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Drug: Mycophenolate Mofetil; Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation; Radiation: Total-Body Irradiation

What is being measured

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

  1. Number of Patients Who Engraft at Each Dose of TBI Used

    Number of subjects who engrafted. Engraftment defined as greater than 95% donor chimerism.

    Measured: Up to Day 200

  2. Incidence of Grades III-IV Acute GVHD

    Number of subjects who developed maximum grade acute graft-vs-host disease

    aGVHD Stages

    Skin:

    1. - a maculopapular eruption involving < 25% BSA
    2. - a maculopapular eruption involving 25 - 50% BSA
    3. - generalized erythroderma
    4. - generalized erythroderma with bullous formation and often with desquamation

    Liver:

    1. - bilirubin 2.0 - 3.0 mg/100 mL
    2. - bilirubin 3 - 5.9 mg/100 mL
    3. - bilirubin 6 - 14.9 mg/100 mL
    4. - bilirubin > 15 mg/100 mL

    Gut:

    Diarrhea is graded 1 - 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as 1 in severity. The severity of gut involvement is assigned to the most severe involvement noted. Patients with visible bloody diarrhea are at least stage 2 gut and grade 3 overall.

    aGVHD Grades Grade III: Stage 2 - 4 gastrointestinal involvement and/or +2 to +4 liver involvement, with or without a rash Grade IV: Pattern and severity of GVHD similar to grade 3 with extreme constitutional symptoms or death

    Measured: Up to Day 100

Secondary outcomes (2)

  1. Incidence of Transplant-related Mortality

    Number of subjects who expired due to transplant-related mortality

    Measured: Up to Day 200

  2. Incidence of Adverse Events

    Number of subjects who developed reportable AEs, assessed using adapted version of the Common Toxicity Criteria

    Measured: Up to Day 100

Timeline

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

  1. First posted28 Mar 2007 (estimated)
  2. Study startFeb 2007
  3. Primary completionJun 2013
  4. Study completionJun 2013

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
Parallel groups
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00453388
Sponsor's protocol ID
2064.00
Other IDs
NCI-2010-00238, 2064.00, P30CA015704
Status last verified
Dec 2019
First submitted
27 Mar 2007
Last updated
29 Jan 2020
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Allogeneic Bone Marrow Transplantation, Cyclophosphamide and Cyclosporine in people with Acute Myeloid Leukemia in Remission and de Novo Myelodysplastic Syndrome, run by Fred Hutchinson Cancer Center at 5 sites in 2 countries.

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 9 inclusion and 13 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: finished, as of the sponsor's last update on 29 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States, Brazil. 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 24 May 2017). 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 Patients Who Engraft at Each Dose of TBI Used (time frame: Up to Day 200). 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 NCT00453388.

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 29 Jan 2020.

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