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Chronic Myelomonocytic LeukemiaPhase 1NCT00988715

Donor Peripheral Blood Stem Cell Transplant and Pretargeted Radioimmunotherapy in Treating Patients With High-Risk Advanced Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Myelodysplastic Syndrome

A Phase 1 study testing Pretargeted Radioimmunotherapy, Cyclosporine and Mycophenolate Mofetil in people with Chronic Myelomonocytic Leukemia and Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable, 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 pretargeted radioimmunotherapy and donor peripheral blood stem cell transplant employing fludarabine phosphate and total-body irradiation (TBI) to treat patients with high-risk acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Pretargeted Radioimmunotherapy, Cyclosporine and Mycophenolate Mofetil
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
1 siteUnited States
Study dates
21 Apr 2010to Jan 2015
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with advanced AML or ALL 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 cytopenia with multilineage dysplasia (RCMD), RCMD with ringed sideroblasts (RCMD-RS), or chronic myelomonocytic leukemia (CMML)
  • Patients not in remission must have CD45-expressing leukemic blasts; patients in remission do not require phenotyping and may have leukemia previously documented to be CD45 negative (because in remission patients, virtually all antibody binding is to nonmalignant cells which make up >= 95% of nucleated cells in the marrow)
  • Patients should have a circulating blast count of less than 10,000/mm^3 (control with hydroxyurea or similar agent is allowed)
  • Patients must have an estimated creatinine clearance greater than 50/mL per minute
  • Bilirubin < 2 times the upper limit of normal
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2 times the upper limit of normal
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  • 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 an 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) or other donor center 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 stem cell source
  • DONOR: Donors must meet HLA matching criteria as well as standard SCCA and/or NMDP, or other donor center criteria for PBSC donation

Who cannot join

  • Circulating human anti-mouse antibody (HAMA) or human anti-streptavidin antibody (HASA)
  • Prior radiation to maximally tolerated levels to any critical normal organ
  • Patients may not have symptomatic coronary artery disease and may not be on cardiac medications for anti-arrhythmic or inotropic effects
  • Patients with the following organ dysfunction:
  • Left ventricular ejection fraction < 35%
  • Corrected diffusion capacity of the lung for carbon monoxide (DLCO) < 35% and/or receiving supplemental continuous oxygen
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  • Liver abnormalities: fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction as evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis, or symptomatic biliary disease
  • Patients who are known seropositive for human immunodeficiency virus (HIV)
  • Perceived inability to tolerate diagnostic or therapeutic procedures, particularly treatment in radiation isolation
  • Active central nervous system (CNS) leukemia
  • Women of childbearing potential who are pregnant (beta-human chorionic gonadotropin [b-HCG] +) or breast feeding
  • Fertile men and women unwilling to use contraceptives during and for 12 months post-transplant
  • Patients may not use vitamin supplements containing biotin from the time of 1 week prior to treatment until 1 week after completion of treatment with all PRIT components
  • Inability to understand or give an informed consent

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: Hematopoietic Cell Transplantation for Patients With High-Risk Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), or Myelodysplastic Syndrome (MDS) Using Radiolabeled DOTA-Biotin Pretargeted by BC8 Antibody-Streptavidin Conjugate

This phase I trial studies pretargeted radioimmunotherapy and donor peripheral blood stem cell transplant employing fludarabine phosphate and total-body irradiation (TBI) to treat patients with high-risk acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome. Giving chemotherapy drugs, such as fludarabine phosphate, and TBI before a donor peripheral blood stem cell transplant helps stop the patient's immune system from rejecting the donor's stem cells. Radiolabeled monoclonal antibodies can be combined with fludarabine phosphate and TBI to find cancer cells and kill them without harming normal cells. Pretargeted radioimmunotherapy (PRIT) allows for further improved targeting of tumor cells over standard directly labeled antibodies.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To estimate the maximum tolerated dose (MTD) of radiation delivered via PRIT using BC8-SA (BC8 antibody-streptavidin conjugate) when combined with fludarabine (FLU) (fludarabine phosphate), 2 Gy total body irradiation (TBI), cyclosporine (CSP), mycophenolate mofetil (MMF), and allogeneic hematopoietic cell transplant (HCT) in patients who have advanced acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or high risk myelodysplastic syndromes (MDS).

SECONDARY OBJECTIVES:

  1. To estimate rates of immune reconstitution, engraftment, and donor chimerism resulting from this combined preparative regimen.

II. To estimate rates of disease relapse, acute graft-versus-host disease (GvHD), and day-100 disease-free survival in patients receiving PRIT using BC8-SA combined with FLU, 2 Gy TBI, CSP, MMF, and allogeneic HCT.

III. To assess biodistribution, serum half-life, urinary excretion, tissue localization, and clearance of BC8-SA conjugate and DOTA-biotin.

IV. To assess the feasibility of yttrium y 90 (90Y)-DOTA-biotin to bind to BC8-SA conjugate localized to hematolymphoid tissues.

OUTLINE:

Patients undergo pretargeted radioimmunotherapy comprising a test dose of BC8-SA conjugate intravenously (IV) on day -22 and indium In 111(111In)-DOTA-biotin IV on day -20, followed by a therapy dose of BC8-SA conjugate IV on day -14 and 90Y-DOTA-biotin IV on day -12. Patients receive fludarabine phosphate IV on days -4 to -2. Patients undergo TBI and then peripheral blood stem cell transplantation on day 0. Patients with matched related donors receive cyclosporine IV on days -3 to 56 and taper to day 180 and mycophenolate mofetil orally (PO) twice daily (BID) on days 0-27. Patients with matched unrelated donors receive cyclosporine IV on days -3 to 100 and taper to day 180 and mycophenolate mofetil PO thrice daily (TID) on days 0-40 and taper to day 96.

After completion of study treatment, patients are followed up at 6, 9, 12, 18, and 24 months, and then annually thereafter.

Being tested
Pretargeted Radioimmunotherapy, Cyclosporine, Mycophenolate Mofetil, Total-Body Irradiation, Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation
Medical subject headings
Leukemia, Myelomonocytic, Chronic, Myeloproliferative Disorders, Precursor Cell Lymphoblastic Leukemia-Lymphoma, 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.

  • Pretargeted RadioimmunotherapyBiological

    Antibody-streptavidin conjugate and radiolabeled DOTA-biotin, each given IV

  • CyclosporineDrug

    Also called 27-400, CsA, Neoral, OL 27-400

    Given IV

  • Mycophenolate MofetilDrug

    Also called Cellcept, MMF

    Given PO

  • Total-Body IrradiationRadiation

    Also called TBI, Total Body Irradiation, Whole-Body Irradiation

    Undergo total-body irradiation

  • Nonmyeloablative Allogeneic Hematopoietic Stem Cell TransplantationProcedure or surgery

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

    Undergo peripheral blood stem cell transplant

  • Peripheral Blood Stem Cell TransplantationProcedure or surgery

    Also called PBPC transplantation, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell Transplantation

    Undergo peripheral blood stem cell transplant

  • Fludarabine PhosphateDrug

    Also called 2-F-ara-AMP, Beneflur, SH T 586

    Given IV

  • Pharmacological StudyOther

    Also called pharmacological studies

    Correlative studies

  • Laboratory Biomarker AnalysisOther

    Correlative studies

Study groups in NCT00988715
Study groupRoleWhat they receive
Treatment (PRIT, transplant)ExperimentalPatients undergo pretargeted radioimmunotherapy comprising a test dose of BC8-SA conjugate IV on day -22 and 111In-DOTA-biotin IV on day -20, followed by a therapy dose of BC8-SA conjugate IV on day -14 and 90Y-DOTA-biotin IV on day -12. Patients receive fludarabine phosphate IV on days -4 to -2. Patients undergo TBI and then peripheral blood stem cell transplant on day 0. Patients with matched related donors receive cyclosporine IV on days -3 to 56 and taper to day 180 and mycophenolate mofetil PO BID on days 0-27. Patients with matched unrelated donors receive cyclosporine IV on days -3 to 100 and taper to day 180 and mycophenolate mofetil PO TID on days 0-40 and taper to day 96.
Receives: Biological: Pretargeted Radioimmunotherapy; Drug: Cyclosporine; Drug: Mycophenolate Mofetil; Radiation: Total-Body Irradiation; Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation; Procedure: Peripheral Blood Stem Cell Transplantation; Drug: Fludarabine Phosphate; Other: Pharmacological Study; Other: Laboratory Biomarker Analysis

What is being measured

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

  1. Incidence of dose-limiting toxicities (DLT) (grade III/IV Bearman) to determine MTD of radiation delivered to normal organ by pretargeted 90Y-DOTA-biotin

    Conducted by the "two-stage" approach introduced by Storer. The MTD will be defined as the dose of 90Y-DOTA-biotin used in combination with the non-myeloablative HCT conditioning regimen that is associated with a grade III/IV regimen related toxicity (RRT) or true DLT rate of 25%.

    Measured: Within 100 days post-transplant

Secondary outcomes (4)

  1. Rates of engraftment, chimerism, and non-relapse mortality

    Chimerism testing methods will be in accordance with Standard Practice Guidelines, with timing consistent with other non-myeloablative transplant protocols. Mixed or full donor chimerism will be evidence of donor engraftment. Full Chimerism is defined as > 95% donor CD3+ T cells and mixed chimerism is the detection of peripheral blood donor T cells (CD3+) and granulocytes (CD33+) as a proportion of the total peripheral blood T cell and granulocyte population, respectively. The true rate of graft rejection exceeds must be less than 20%.

    Measured: Days 28

  2. Rates of engraftment, chimerism, and non-relapse mortality

    Chimerism testing methods will be in accordance with Standard Practice Guidelines, with timing consistent with other non-myeloablative transplant protocols. Mixed or full donor chimerism will be evidence of donor engraftment. Full Chimerism is defined as > 95% donor CD3+ T cells and mixed chimerism is the detection of peripheral blood donor T cells (CD3+) and granulocytes (CD33+) as a proportion of the total peripheral blood T cell and granulocyte population, respectively. The true rate of graft rejection exceeds must be less than 20%.

    Measured: Day 84

  3. Rate of grades III-IV acute GVHD

    Graded according to the established criteria at the FHCRC.

    Measured: At day +100

  4. Achievement and duration of response

    Complete remission is defined as complete resolution of all signs of myelodysplasia or leukemia for at least four weeks with normal bone marrow with blasts < 5% with normal cellularity, normal megakaryopoiesis, more than 15% erythropoiesis, and more than 25% granulocytopoiesis; normalization of blood counts; and no extramedullary disease. Partial remission is defined as improvement of hematological parameters in the peripheral blood and 50% decline in marrow blasts from pre-transplant level with > 10% erythropoiesis and 25% granulocytopoiesis.

    Measured: Up to 24 months

Timeline

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

  1. First posted2 Oct 2009 (estimated)
  2. Study start21 Apr 2010
  3. Primary completionJan 2015

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
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00988715
Sponsor's protocol ID
2309.00
Other IDs
NCI-2009-01294, 2309.00, P01CA044991, P30CA015704
Status last verified
Aug 2017
First submitted
1 Oct 2009
Last updated
30 Aug 2017
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Pretargeted Radioimmunotherapy, Cyclosporine and Mycophenolate Mofetil in people with Chronic Myelomonocytic Leukemia and Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable, 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 14 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 30 Aug 2017. 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?

Incidence of dose-limiting toxicities (DLT) (grade III/IV Bearman) to determine MTD of radiation delivered to normal organ by pretargeted 90Y-DOTA-biotin (time frame: Within 100 days 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 NCT00988715.

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 30 Aug 2017.

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