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Adult Acute Myeloid Leukemia in RemissionPhase 1NCT00008177

Radiolabeled Monoclonal Antibody Therapy, Fludarabine Phosphate, and Low-Dose Total-Body Irradiation Followed by Donor Stem Cell Transplant and Immunosuppression Therapy in Treating Older Patients With Advanced Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes

A Phase 1 study testing iodine I 131 monoclonal antibody BC8, total-body irradiation and allogeneic hematopoietic stem cell transplantation in people with Adult Acute Myeloid Leukemia in Remission and Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, run by Fred Hutchinson Cancer Center at 1 site in United States.

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 I trial studies the side effects and best dose of iodine I 131 monoclonal antibody BC8 when given together with fludarabine phosphate and low-dose total-body irradiation followed by donor stem cell transplant and immunosuppression therapy in treating older patients with acute myeloid leukemia or high-risk… Read more about this study

Who is it for?
Ages 50 years and older
What is being tested?
iodine I 131 monoclonal antibody BC8, total-body irradiation and allogeneic hematopoietic stem cell transplantation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
79 participants
Where
1 siteUnited States
Study dates
27 Jul 1999to 15 Dec 2010
Phase
Phase 1
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 50 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with advanced AML defined as beyond first remission, primary refractory disease, or evolved from myelodysplastic or myeloproliferative syndromes; or patients with MDS expressed as refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEBT [Note: classification removed under current World Health Organization [WHO] classification system]), refractory cytopenia with multilineage dysplasia (RCMD), RCMD with ringed sideroblasts (RCMD-RS), or chronic myelomonocytic leukemia (CMML)
  • Patients in relapse must have documented cluster of differentiation (CD)45 expression by their myelodysplastic or leukemic cells to be studied and treated with 131I-labeled BC8 antibody; patients in remission do not require phenotyping and may have leukemia previously documented to be CD45 negative
  • Patients should have a circulating blast count of less than 10,000/mm^3 (control with hydroxyurea or similar agent is allowed)
  • Patients must undergo a 24-hour urine collection with documented creatinine clearance > 50 ml/min
  • Bilirubin < 2 times the upper limit of normal
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2 times the upper limit of normal
Show all 10Show fewer
  • Karnofsky score >= 70 or Eastern Cooperative Oncology Group (ECOG) =< 2
  • Patients must have an expected survival of > 60 days and must be free of active infection
  • Patients must have a human leukocyte antigen (HLA)-identical sibling donor or an HLA-matched unrelated donor who meets standard Seattle Cancer Care Alliance (SCCA) and/or National Marrow Donor Program (NMDP) criteria for peripheral blood stem cell (PBSC) donation; related donors should be matched by molecular methods at the intermediate resolution level at HLA-A, B, C, and DRB1 according to Fred Hutchinson Cancer Research Center (FHCRC) Standard Practice Guidelines and to the allele level at DQB1; unrelated donors should be identified using matching criteria that follows the FHCRC Standard Practice Guidelines limiting the study to eligible donors that are allele matched for HLA-A, B, C, DRB1, and DQB1 (grade 1), and accepting up to one allele mismatch as per standard practice grade 2.1 for HLA-A, B, or C; PBSC is the only permitted hematopoietic stem cell (HSC) source
  • DONOR: Donors must meet HLA matching criteria as outlined above as well as standard Seattle Cancer Care Alliance (SCCA) and/or NMDP criteria for PBSC donation

Who cannot join

  • Circulating antibody against mouse immunoglobulin (human anti-mouse antibody [HAMA])
  • Prior radiation to maximally tolerated levels to any normal organ
  • Patients may not have symptomatic coronary artery disease and may not be on cardiac medications for anti-arrhythmic or inotropic effects
  • Inability to understand or give an informed consent
  • Patients who are seropositive for human immunodeficiency virus (HIV)
  • Perceived inability to tolerate diagnostic or therapeutic procedures, particularly treatment in radiation isolation
  • Patients who have previously undergone marrow or PBSC transplantation

Trial locations and contacts

1 site in 1 country.

United States1 site

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

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: A Phase I Study Combining Escalating Doses of Radiolabeled BC8 (Anti-CD45) Antibody With Fludarabine, Low Dose TBI, PBSC Infusion and Post-Transplant Immunosuppression With Cyclosporine and Mycophenolate Mofetil to Establish Mixed or Full Donor Chimerism for Elderly Patients With Advanced Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome

This phase I trial studies the side effects and best dose of iodine I 131 monoclonal antibody BC8 when given together with fludarabine phosphate and low-dose total-body irradiation followed by donor stem cell transplant and immunosuppression therapy in treating older patients with acute myeloid leukemia or high-risk myelodysplastic syndromes that cannot be controlled with treatment. Radiolabeled monoclonal antibodies, such as iodine I 131 monoclonal antibody BC8, can find cancer cells and carry cancer-killing substances to them. Giving chemotherapy, such as fludarabine phosphate, and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer or abnormal cells. It may also 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. The donated stem cells may also replace the patient's immune cells and help destroy any remaining cancer cells. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving radiolabeled monoclonal antibody therapy together with fludarabine phosphate and total-body irradiation before the transplant together with cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximum tolerated dose of radiation delivered via 131I-BC8 antibody (iodine I 131 monoclonal antibody BC8) when combined with the non-myeloablative regimen of fludarabine (fludarabine phosphate), 2 Gy total-body irradiation (TBI) + cyclosporine (CSP)/mycophenolate (MMF) in elderly patients with advanced acute myeloid leukemia (AML) or high risk myelodysplastic syndromes (MDS).

II. To determine the rates of donor chimerism resulting from this combined preparative regimen, and to correlate level of donor chimerism with estimated radiation doses delivered to hematopoietic tissues via antibody.

III. To determine, within the limits of a phase I study, disease response and duration of remission.

IV. To assess dose-limiting toxicity (DLT) at the estimated maximum tolerated dose (MTD) of 131I-BC8 (24 Gy) in order to gain more confidence that the DLT rate is acceptable at this level.

OUTLINE: This is a dose-escalation study of iodine I 131 monoclonal antibody BC8.

CONDITIONING REGIMEN: Patients receive iodine I 131 monoclonal antibody BC8 intravenously (IV) on day -12 and fludarabine phosphate IV on days -4 to -2. Patients undergo total-body irradiation on day 0.

TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation on day 0.

IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) or IV twice daily (BID) on days -3 to 56 with taper to day 80 (for patients with a related donor) OR days -3 to 100 with taper to day 177 (for patients with an unrelated donor) in the absence of graft-versus-host disease (GVHD). Patients also receive mycophenolate mofetil PO or IV thrice daily (TID) on days 0 to 27 (for patients with a related donor) OR on days 0 to 40 with taper to day 96 (for patients with an unrelated donor) in the absence of GVHD.

After completion of study treatment, patients are followed up at 6, 9, and 12 months, every 6 months for 1 year, and then yearly thereafter.

Medical subject headings
Congenital Abnormalities, Leukemia, Myelomonocytic, Chronic, Leukemia, Myeloid, Acute, Anemia, Refractory, with Excess of Blasts

What participants receive

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

  • iodine I 131 monoclonal antibody BC8Radiation

    Also called I 131 MOAB BC8, I 131 Monoclonal Antibody BC8, iodine I 131 MOAB BC8

    Given IV

  • total-body irradiationRadiation

    Also called TBI

    Undergo total-body irradiation

  • allogeneic hematopoietic stem cell transplantationProcedure or surgery

    Undergo allogeneic peripheral blood stem cell transplantation

  • peripheral blood stem cell transplantationProcedure or surgery

    Also called PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell

    Undergo allogeneic peripheral blood stem cell transplantation

  • fludarabine phosphateDrug

    Also called 2-F-ara-AMP, Beneflur, Fludara

    Given IV

  • cyclosporineDrug

    Also called ciclosporin, cyclosporin, cyclosporin A, CYSP

    Given orally or IV

  • mycophenolate mofetilDrug

    Also called Cellcept, MMF

    Given orally or IV

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT00008177
Study groupRoleWhat they receive
Treatment ( I 131 BC8, chemotherapy, TBI, PBSCT, CSP, MMF)ExperimentalCONDITIONING REGIMEN: Patients receive iodine I 131 monoclonal antibody BC8 IV on day -12 and fludarabine phosphate IV on days -4 to -2. Patients undergo total-body irradiation on day 0. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine PO or IV BID on days -3 to 56 with taper to day 80 (for patients with a related donor) OR days -3 to 100 with taper to day 177 (for patients with an unrelated donor) in the absence of GVHD. Patients also receive mycophenolate mofetil PO or IV TID on days 0 to 27 (for patients with a related donor) OR on days 0 to 40 with taper to day 96 (for patients with an unrelated donor) in the absence of GVHD.
Receives: Radiation: iodine I 131 monoclonal antibody BC8; Radiation: total-body irradiation; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation; Drug: fludarabine phosphate; Drug: cyclosporine; Drug: mycophenolate mofetil; Other: laboratory biomarker analysis

What is being measured

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

  1. Maximum tolerated dose of radiation delivered via 131I-BC8 antibody when combined with the nonmyeloablative regimen of fludarabine phosphate, TBI, and CSP/MMF

    Measured: Up to day 100 following transplant

  2. Rates of donor chimerism resulting from this combined preparative regimen

    Correlated with estimated radiation doses delivered to hematopoietic tissues via antibody.

    Measured: Up to day 84 following transplant

  3. Disease response

    Measured: Up to 11 years

  4. Duration of remission

    Measured: Up to 11 years

  5. incidence of DLT at the estimated MTD of 131I-BC8

    Measured: Up to day 100 following transplant

Timeline

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

  1. First posted12 Dec 2003 (estimated)
  2. Study start27 Jul 1999
  3. Primary completion21 Mar 2009
  4. Study completion15 Dec 2010

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
79 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00008177
Sponsor's protocol ID
1432.00
Other IDs
NCI-2010-02046, 1432, 1432.00, P30CA015704, P01CA044991
Status last verified
Nov 2019
First submitted
6 Jan 2001
Last updated
13 Nov 2019
Results posted
No
Data monitoring committee
Yes

Publications

  • Pagel JM, Gooley TA, Rajendran J, Fisher DR, Wilson WA, Sandmaier BM, Matthews DC, Deeg HJ, Gopal AK, Martin PJ, Storb RF, Press OW, Appelbaum FR. Allogeneic hematopoietic cell transplantation after conditioning with 131I-anti-CD45 antibody plus fludarabine and low-dose total body irradiation for elderly patients with advanced acute myeloid leukemia or high-risk myelodysplastic syndrome. Blood. 2009 Dec 24;114(27):5444-53. doi: 10.1182/blood-2009-03-213298. Epub 2009 Sep 28.

    PubMed 19786617

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing iodine I 131 monoclonal antibody BC8, total-body irradiation and allogeneic hematopoietic stem cell transplantation in people with Adult Acute Myeloid Leukemia in Remission and Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, run by Fred Hutchinson Cancer Center 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 10 inclusion and 7 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 13 Nov 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Maximum tolerated dose of radiation delivered via 131I-BC8 antibody when combined with the nonmyeloablative regimen of fludarabine phosphate, TBI, and CSP/MMF (time frame: Up to day 100 following transplant). The study lists 5 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 NCT00008177, which also lists 1 linked publication.

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 13 Nov 2019.

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