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Chronic Myelomonocytic LeukemiaPhase 1NCT01300572

Yttrium-90 Anti-CD45 Monoclonal Antibody BC8 Followed by Donor Stem Cell Transplant in Treating Patients With High-Risk AML, ALL, or MDS

A Phase 1 study testing Allogeneic Bone Marrow Transplantation, Allogeneic Hematopoietic Stem Cell Transplantation and Cyclosporine in people with Chronic Myelomonocytic Leukemia and Previously Treated Myelodysplastic Syndrome, 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
Search all trials

Trial summary

This phase I trial studies the side effects and maximum tolerated dose of yttrium Y 90 anti-cluster of differentiation 45 (CD45) monoclonal antibody BC8 (90Y-BC8) followed by donor stem cell transplant in treating patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or myelodysplastic… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Allogeneic Bone Marrow Transplantation, Allogeneic Hematopoietic Stem Cell Transplantation and Cyclosporine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
1 siteUnited States
Study dates
Jan 2012to 22 Nov 2019
Phase
Phase 1
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have advanced AML, ALL or high-risk MDS meeting one of the following descriptions:
  • AML or ALL beyond first remission (i.e., having relapsed at least one time after achieving remission in response to a treatment regimen)
  • AML or ALL representing primary refractory disease (i.e., having failed to achieve remission at any time following one or more prior treatment regimens)
  • AML evolved from myelodysplastic or myeloproliferative syndromes; or
  • MDS expressed as refractory anemia with excess blasts (RAEB) or chronic myelomonocytic leukemia (CMML) by French-American-British (FAB) criteria
  • 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 non-malignant cells which make up >= 95% of nucleated cells in the marrow)
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  • 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 (serum creatinine value must be within 28 days prior to registration)
  • Bilirubin < 2 times the upper limit of normal
  • Aspartate aminotransferase (AST) and alanine transaminase (ALT) < 2 times the upper limit of normal
  • Eastern Cooperative Oncology Group (ECOG) =< 2 or Karnofsky >= 70
  • 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 PBSC or bone marrow donation, as follows:
  • Related donor: related to the patient and genotypically or phenotypically identical for HLA-A, B, C, DRB1 and DQB1; phenotypic identity must be confirmed by high-resolution typing
  • Unrelated donor:
  • Matched for HLA-A, B, C, DRB1 and DQB1 by high resolution typing; OR mismatched for a single allele without antigen mismatching at HLA-A, B or C as defined by high resolution typing but otherwise matched for HLA-A, B, C, DRB1 and DQB1 by high resolution typing
  • Doors are excluded when preexisting immunoreactivity is identified that would jeopardize donor hematopoietic cell engraftment; this determination is based on the standard practice of the individual institution; the recommended procedure for patients with 10 of 10 HLA allele level (phenotypic) match is to obtain panel reactive antibody (PRA) screens to class I and class II antigens for all patients before hematopoietic cell transplant (HCT); if the PRA shows > 10% activity, then flow cytometric or B and T cell cytotoxic cross matches should be obtained; the donor should be excluded if any of the cytotoxic cross match assays are positive; for those patients with and HLA class I allele mismatch, flow cytometric or B and T cell cytotoxic cross matches should be obtained regardless of the PRA results; a positive anti-donor cytotoxic crossmatch is an absolute donor exclusion
  • Patient and donor pairs homozygous at a mismatched allele in the graft rejection vector are considered a two-allele mismatch; i.e., the patient is A*0101 and the donor is A*0102, and this type of mismatch is not allowed
  • DONOR: Donors must meet HLA matching criteria and standard SCCA and/or National Marrow Donor Program (NMDP) or other donor center criteria for PBSC or bone marrow donation

Who cannot join

  • Circulating human anti-mouse antibody (HAMA)
  • Prior radiation to maximally tolerated levels to any critical normal organ, or > 20 Gy prior radiation to large areas of the bone marrow (e.g., external radiation therapy to whole pelvis)
  • Patients may not have symptomatic coronary artery disease and may not be on cardiac medications for anti-arrhythmic or inotropic effects
  • Left ventricular ejection fraction < 35%
  • Corrected diffusion lung capacity of carbon monoxide (DLCO) < 35% or receiving supplemental continuous oxygen
  • 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
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  • Patients who are known to be seropositive for human immunodeficiency virus (HIV)
  • Perceived inability to tolerate diagnostic or therapeutic procedures
  • Active central nervous system (CNS) leukemia at time of treatment
  • Women of childbearing potential who are pregnant (beta-human chorionic gonadotropin positive [HCG+]) or breast feeding
  • Fertile men and women unwilling to use contraceptives during and for 12 months post-transplant
  • Inability to understand or give an informed consent

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: A Study Evaluating Escalating Doses of 90Y-DOTA-BC8 (Anti-CD45) Antibody Followed by Allogeneic Stem Cell Transplantation for High-Risk Acute Myeloid Leukemia (AML) Acute Lymphoblastic Leukemia (ALL), or Myelodysplastic Syndrome (MDS)

This phase I trial studies the side effects and maximum tolerated dose of yttrium Y 90 anti-cluster of differentiation 45 (CD45) monoclonal antibody BC8 (90Y-BC8) followed by donor stem cell transplant in treating patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or myelodysplastic syndrome (MDS) that is likely to come back or spread. Giving chemotherapy drugs, such as fludarabine phosphate (FLU), and total-body irradiation (TBI) before a donor peripheral blood stem cell (PBSC) or bone marrow transplant helps stop the growth of cancer or abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. Radiolabeled monoclonal antibodies, such as 90Y-BC8, can find cancer cells and carry cancer-killing substances to them without harming normal 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. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving FLU, 90Y-BC8, and TBI 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 estimate the maximum tolerated dose (MTD) of radiation delivered via 90Y-DOTA-BC8 (90Y-BC8) when combined with FLU and 2 Gy TBI as a preparative regimen for patients aged >= 18 with advanced AML, ALL, and high-risk MDS.

SECONDARY OBJECTIVES:

  1. To determine disease response and duration of remission.

II. To determine the rates of engraftment and 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.

OUTLINE:

PREPARATIVE REGIMEN: Patients receive 90Y-BC8 via central line on approximately day -12 and FLU intravenously (IV) over 30 minutes on days -4 to -2.

TRANSPLANTATION: Patients undergo TBI followed by allogeneic PBSC or bone marrow transplant on day 0.

GRAFT-VS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive mycophenolate mofetil orally (PO) or IV every 12 hours on days 0-27 (for patients with related donors) or every 8 hours on days 0-40 with taper to day 96 (for patients with unrelated donors). Patients also receive cyclosporine PO or IV every 12 hours on days -3 to 56 (for patients with related donors) or 100 (for patients with unrelated donors) with taper to day 180.

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

Being tested
Allogeneic Bone Marrow Transplantation, Allogeneic Hematopoietic Stem Cell Transplantation, Cyclosporine, Fludarabine Phosphate, Indium In 111 Anti-CD45 Monoclonal Antibody BC8
Medical subject headings
Leukemia, Myelomonocytic, Chronic, 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.

  • Allogeneic Bone Marrow TransplantationProcedure or surgery

    Also called Allo BMT, Allogeneic BMT

    Undergo allogeneic bone marrow transplant

  • Allogeneic Hematopoietic Stem Cell TransplantationProcedure or surgery

    Also called allogeneic stem cell transplantation, HSC, HSCT

    Undergo allogeneic PBSC or bone marrow transplant

  • CyclosporineDrug

    Also called 27-400, Ciclosporin, CsA, Cyclosporin

    Given PO or IV

  • 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

  • Indium In 111 Anti-CD45 Monoclonal Antibody BC8Biological

    Also called In 111 MOAB BC8, In 111 Monoclonal Antibody BC8, Indium In 111 Monoclonal Antibody BC8, monoclonal antibody BC8, indium In 111

    Given IV (dosimetric dose)

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Mycophenolate MofetilDrug

    Also called Cellcept, MMF

    Given PO or IV

  • 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 allogeneic PBSC transplant

  • Pharmacological StudyOther

    Correlative studies

  • Total-Body IrradiationRadiation

    Also called TOTAL BODY IRRADIATION, Whole-Body Irradiation

    Undergo TBI

  • Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8Radiation

    Also called 90Y Anti-CD45 MoAb BC8

    Given via central line (therapeutic dose)

Study groups in NCT01300572
Study groupRoleWhat they receive
Y-90-BC8 & Allogeneic TransplantExperimentalPREPARATIVE REGIMEN: Patients receive 90Y-BC8 via central line on approximately day -12, fludarabine phosphate IV over 30 minutes on days -4 to -2, and 2 Gy TBI on day 0. TRANSPLANTATION: Patients undergo allogeneic PBSC or bone marrow transplant on day 0. GVHD PROPHYLAXIS: Patients receive mycophenolate mofetil PO or IV every 12 hours on days 0-27 (for patients with related donors) or every 8 hours on days 0-40 with taper to day 96 (for patients with unrelated donors). Patients also receive cyclosporine PO or IV every 12 hours on days -3 to 56 (for patients with related donors) or 100 (for patients with unrelated donors) with taper to day 180.
Receives: Procedure: Allogeneic Bone Marrow Transplantation; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Cyclosporine; Drug: Fludarabine Phosphate; Biological: Indium In 111 Anti-CD45 Monoclonal Antibody BC8; Other: Laboratory Biomarker Analysis; Drug: Mycophenolate Mofetil; Procedure: Peripheral Blood Stem Cell Transplantation; Other: Pharmacological Study; Radiation: Total-Body Irradiation; Radiation: Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8

What is being measured

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

  1. The MTD of Radiation Delivered Via 90Y-DOTA-BC8 When Combined With FLU and 2 Gy TBI as a Preparative Regimen for Patients Aged ≥ 18 With Advanced AML, ALL, and High-risk MDS.

    The MTD will be defined as the dose that is associated with a true DLT rate of 25%. The highest dose achieved was 28 Gy but none of the patients experienced a DLT. Thus, the MTD was not reached.

    Measured: Within the first 30 days following transplant

Secondary outcomes (9)

  1. Achievement of Remission

    Number of participants who are in complete remission (CR) 4 weeks after transplant. CR is defined as complete resolution of all signs of myelodysplasia or leukemia for at least 4 weeks with all of the following:

    1. Normal bone marrow with blasts <5% with normal cellularity, normal megakaryopoiesis, > 15% erythropoiesis and > 25% granulocytopoiesis
    2. Normalization of blood counts (no blasts, platelets > 100000/mm3, granulocytes >1500/mm3)
    3. No extramedullary disease.

    Measured: 4 weeks after transplant

  2. Disease-free Survival

    Number of study participants who are alive and remains in complete remission after transplant.

    Measured: 100 days after transplant

  3. Duration of Remission

    Median time to relapse after achieving complete remission (CR). CR is defined as complete resolution of all signs of myelodysplasia or leukemia for at least 4 weeks with all of the following:

    1. Normal bone marrow with blasts <5% with normal cellularity, normal megakaryopoiesis, > 15% erythropoiesis and > 25% granulocytopoiesis
    2. Normalization of blood counts (no blasts, platelets > 100000/mm3, granulocytes >1500/mm3)
    3. No extramedullary disease.

    Relapse Criteria:

    1. After CR: >5% blasts in the bone marrow and/or peripheral blood
    2. After partial remission (PR): increase of blasts cells in the marrow to >50% of those during PR
    3. Extramedullary disease confirmed cytologically or histologically.

    Measured: 1 year

  4. Estimation of Absorbed Radiation Doses to Normal Organs, Marrow and Tumor

    The amount of energy absorbed per unit weight of the organ or tissue is called absorbed dose and is expressed in units of gray (Gy). One gray dose is equivalent to one joule radiation energy absorbed per kilogram of organ or tissue weight.

    Measured: Approximately day -20 to day -12 prior to transplant

  5. Overall Survival

    Number of participants who are still alive after transplant with or without disease.

    Measured: Up to 5 years

  6. Rates of Acute GvHD

    Number of participants who developed acute GVHD post-transplant, aGVHD stages:

    Skin: a maculopapular eruption involving < 25% BSA a maculopapular eruption involving 25 - 50% BSA generalized erythroderma generalized erythroderma with bullous formation and often with desquamation

    Liver:

    bilirubin 2.0 - 3.0 mg/100 mL bilirubin 3 - 5.9 mg/100 mL bilirubin 6 - 14.9 mg/100 mL 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 gut involvement and/or stage 2 - 4 liver involvement Grade IV: Pattern and severity of GVHD similar to grade 3 with extreme constitutional symptoms or death

    Measured: Up to 84 days post-transplant

  7. Rates of Donor Chimerism

    Number of participants who has 100% donor chimerism within 100 days after transplant

    Measured: Up to 100 days post-transplant

  8. Rates of Engraftment

    Average number of days to ANC >= 500 after transplant

    Measured: Up to 84 days post-transplant

  9. Rates of Non-relapse Mortality

    Transplant-related deaths within 100 days after transplant

    Measured: Within the first 100 days 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 posted21 Feb 2011 (estimated)
  2. Study startJan 2012
  3. Primary completion29 Oct 2017
  4. Study completion22 Nov 2019

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
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01300572
Sponsor's protocol ID
2468.00
Other IDs
NCI-2011-00150, 2468.00A, 2468, 2468.00, P01CA044991, P30CA015704
Status last verified
Dec 2019
First submitted
15 Feb 2011
Last updated
10 Dec 2019
Data monitoring committee
Yes

Publications

  • Vo P, Gooley TA, Rajendran JG, Fisher DR, Orozco JJ, Green DJ, Gopal AK, Haaf R, Nartea M, Storb R, Appelbaum FR, Press OW, Pagel JM, Sandmaier BM. Yttrium-90-labeled anti-CD45 antibody followed by a reduced-intensity hematopoietic cell transplantation for patients with relapsed/refractory leukemia or myelodysplasia. Haematologica. 2020 Jun;105(6):1731-1737. doi: 10.3324/haematol.2019.229492. Epub 2019 Oct 3.

    PubMed 31582553

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Allogeneic Bone Marrow Transplantation, Allogeneic Hematopoietic Stem Cell Transplantation and Cyclosporine in people with Chronic Myelomonocytic Leukemia and Previously Treated Myelodysplastic Syndrome, 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 19 inclusion and 12 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 10 Dec 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?

Yes. Results are posted in the registry (first posted 25 Jan 2019). 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?

The MTD of Radiation Delivered Via 90Y-DOTA-BC8 When Combined With FLU and 2 Gy TBI as a Preparative Regimen for Patients Aged ≥ 18 With Advanced AML, ALL, and High-risk MDS. (time frame: Within the first 30 days following 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 NCT01300572, 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 10 Dec 2019.

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