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NCT00589316

Iodine I 131 Monoclonal Antibody BC8, Fludarabine Phosphate, Cyclophosphamide, Total-Body Irradiation and Donor Bone Marrow Transplant in Treating Patients With Advanced Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or High-Risk Myelodysplastic Syndrome

Terminated Phase 1 Results posted Last updated 9 February 2023
What this trial tests

Phase 1 trial testing Allogeneic Bone Marrow Transplantation in Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome in 26 participants. Terminated before completion.

Timeline
5 October 2007
Primary endpoint
1 October 2016
1 October 2021

Quick facts

Lead sponsorFred Hutchinson Cancer Center
PhasePhase 1
StatusTerminated
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment26
Start date5 October 2007
Primary completion1 October 2016
Estimated completion1 October 2021
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Fred Hutchinson Cancer Center — full company profile →

Who can join

18 and older, any sex, with Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome or Adult Acute Lymphoblastic Leukemia in Remission. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Dose-limiting Toxicities (DLT) 30 Days After Transplant Primary · Up to 30 days post-transplant

The criteria of Grade III/IV regimen-related toxicity (Bearman) or dose-limiting toxicity (DLT) are as follows: Grade 1 Development of transient chemical abnormalities which are not of major clinical consequence and which reverse without requiring major medical interventions. In general, the intent of this toxicity scale is to observe transient target organ toxicity which is reversible. Grade 2 Development of chemical or laboratory abnormalities that are persistent and which may represent target organ damage that may not be readily reversed. It is anticipated that at this dose of the drug, t

GroupValue95% CI
Dose Level 1: 12 Gy Iodine-131 + BC8 Monoclonal Antibody1
Dose Level 2: 14 Gy Iodine-131 + BC8 Monoclonal Antibody1
Dose Level 3: 16 Gy Iodine-131 + BC8 Monoclonal Antibody5
Dose Level 4: 18 Gy Iodine-131 + BC8 Monoclonal Antibody1
Dose Level 5: 20 Gy Iodine-131 + BC8 Monoclonal Antibody1
Dose Level 6: 22 Gy Iodine-131 + BC8 Monoclonal Antibody2
Dose Level 7: 24 Gy Iodine-131 + BC8 Monoclonal Antibody6
Dose Level 8: 26 Gy Iodine-131 + BC8 Monoclonal Antibody7
Dose Level 1: 12 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 2: 14 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 3: 16 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 4: 18 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 5: 20 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 6: 22 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 7: 24 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 8: 26 Gy Iodine-131 + BC8 Monoclonal Antibody1
Number of Participants With Transplant-Related Mortality Within 100 Days After Transplant Secondary · Up to 100 days post-transplant

Number of Participants that received and completed study treatment who died within 100 days after transplant

GroupValue95% CI
Dose Level 1: 12 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 2: 14 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 3: 16 Gy Iodine-131 + BC8 Monoclonal Antibody1
Dose Level 4: 18 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 5: 20 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 6: 22 Gy Iodine-131 + BC8 Monoclonal Antibody1
Dose Level 7: 24 Gy Iodine-131 + BC8 Monoclonal Antibody2
Dose Level 8: 26 Gy Iodine-131 + BC8 Monoclonal Antibody1
Dose Level 1: 12 Gy Iodine-131 + BC8 Monoclonal Antibody1
Dose Level 2: 14 Gy Iodine-131 + BC8 Monoclonal Antibody1
Dose Level 3: 16 Gy Iodine-131 + BC8 Monoclonal Antibody4
Dose Level 4: 18 Gy Iodine-131 + BC8 Monoclonal Antibody1
Dose Level 5: 20 Gy Iodine-131 + BC8 Monoclonal Antibody1
Dose Level 6: 22 Gy Iodine-131 + BC8 Monoclonal Antibody1
Dose Level 7: 24 Gy Iodine-131 + BC8 Monoclonal Antibody5
Dose Level 8: 26 Gy Iodine-131 + BC8 Monoclonal Antibody6
Participant Disease Response Within 90 Days After Transplant Secondary · Up to 90 days after transplant

The number of participants that are in complete remission or relapsed within 90 days after transplant Complete Remission is defined as the complete resolution of all signs of leukemia for at least 90 days with all of the following: 1. Normal bone marrow with blasts \<5% with normal cellularity, normal megakarypoiesis, more than 15% erythropoiesis, and more than 25% granulocytopoiesis. 2. Normalization of blood counts (no blasts, platelets \> 100000/mm3, granulocytes \>1500/mm3) 3. No extramedullary disease Relapse is measured as follows: 1. After CR: \>5% blasts in the bone marrow and/or p

GroupValue95% CI
Dose Level 1: 12 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 2: 14 Gy Iodine-131 + BC8 Monoclonal Antibody1
Dose Level 3: 16 Gy Iodine-131 + BC8 Monoclonal Antibody2
Dose Level 4: 18 Gy Iodine-131 + BC8 Monoclonal Antibody1
Dose Level 5: 20 Gy Iodine-131 + BC8 Monoclonal Antibody1
Dose Level 6: 22 Gy Iodine-131 + BC8 Monoclonal Antibody1
Dose Level 7: 24 Gy Iodine-131 + BC8 Monoclonal Antibody4
Dose Level 8: 26 Gy Iodine-131 + BC8 Monoclonal Antibody3
Dose Level 1: 12 Gy Iodine-131 + BC8 Monoclonal Antibody1
Dose Level 2: 14 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 3: 16 Gy Iodine-131 + BC8 Monoclonal Antibody2
Dose Level 4: 18 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 5: 20 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 6: 22 Gy Iodine-131 + BC8 Monoclonal Antibody1
Dose Level 7: 24 Gy Iodine-131 + BC8 Monoclonal Antibody3
Dose Level 8: 26 Gy Iodine-131 + BC8 Monoclonal Antibody3
Dose Level 1: 12 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 2: 14 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 3: 16 Gy Iodine-131 + BC8 Monoclonal Antibody1
Dose Level 4: 18 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 5: 20 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 6: 22 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 7: 24 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 8: 26 Gy Iodine-131 + BC8 Monoclonal Antibody1
Severity of Acute GVHD in Patients Who Completed the Study Treatment Secondary · 100 days after transplant

The severity of acute GVHD is measured based on Graft vs Host Disease: Grade I +1 to +2 skin rash No gut or liver involvement Grade II +3 skin rash or * 1 gastrointestinal involvement and/or +1 liver involvement Grade III +2 to +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

GroupValue95% CI
Dose Level 1: 12 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 2: 14 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 3: 16 Gy Iodine-131 + BC8 Monoclonal Antibody1
Dose Level 4: 18 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 5: 20 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 6: 22 Gy Iodine-131 + BC8 Monoclonal Antibody1
Dose Level 7: 24 Gy Iodine-131 + BC8 Monoclonal Antibody1
Dose Level 8: 26 Gy Iodine-131 + BC8 Monoclonal Antibody1
Dose Level 1: 12 Gy Iodine-131 + BC8 Monoclonal Antibody1
Dose Level 2: 14 Gy Iodine-131 + BC8 Monoclonal Antibody1
Dose Level 3: 16 Gy Iodine-131 + BC8 Monoclonal Antibody1
Dose Level 4: 18 Gy Iodine-131 + BC8 Monoclonal Antibody1
Dose Level 5: 20 Gy Iodine-131 + BC8 Monoclonal Antibody1
Dose Level 6: 22 Gy Iodine-131 + BC8 Monoclonal Antibody1
Dose Level 7: 24 Gy Iodine-131 + BC8 Monoclonal Antibody3
Dose Level 8: 26 Gy Iodine-131 + BC8 Monoclonal Antibody4
Dose Level 1: 12 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 2: 14 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 3: 16 Gy Iodine-131 + BC8 Monoclonal Antibody2
Dose Level 4: 18 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 5: 20 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 6: 22 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 7: 24 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 8: 26 Gy Iodine-131 + BC8 Monoclonal Antibody1
Dose Level 1: 12 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 2: 14 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 3: 16 Gy Iodine-131 + BC8 Monoclonal Antibody1
Dose Level 4: 18 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 5: 20 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 6: 22 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 7: 24 Gy Iodine-131 + BC8 Monoclonal Antibody3
Dose Level 8: 26 Gy Iodine-131 + BC8 Monoclonal Antibody1
Number of Participants With 100% Donor Chimerism at Day 84 Secondary · Day 84 after transplant

Post-transplant bone marrow and peripheral blood samples were collected on day 84 after transplant for DNA Chimerism Analysis

GroupValue95% CI
Dose Level 1: 12 Gy Iodine-131 + BC8 Monoclonal Antibody1
Dose Level 2: 14 Gy Iodine-131 + BC8 Monoclonal Antibody1
Dose Level 3: 16 Gy Iodine-131 + BC8 Monoclonal Antibody5
Dose Level 4: 18 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 5: 20 Gy Iodine-131 + BC8 Monoclonal Antibody1
Dose Level 6: 22 Gy Iodine-131 + BC8 Monoclonal Antibody1
Dose Level 7: 24 Gy Iodine-131 + BC8 Monoclonal Antibody4
Dose Level 8: 26 Gy Iodine-131 + BC8 Monoclonal Antibody6
Dose Level 1: 12 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 2: 14 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 3: 16 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 4: 18 Gy Iodine-131 + BC8 Monoclonal Antibody1
Dose Level 5: 20 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 6: 22 Gy Iodine-131 + BC8 Monoclonal Antibody1
Dose Level 7: 24 Gy Iodine-131 + BC8 Monoclonal Antibody3
Dose Level 8: 26 Gy Iodine-131 + BC8 Monoclonal Antibody1
Two-Year Disease-free Survival of Study Participants Who Completed the Study Regimen Secondary · 2 years post-transplant

Survival and complete resolution of all signs of leukemia 2 years after transplant with all of the following: 1, Normal bone marrow with blasts \<5% with normal cellularity, normal megakaryopoiesis, more than 15% erythropoiesis, and more than 25% granulocytopoiesis. 2\. Normalization of blood counts (no basts, platelets \>100,000/mm3, granulocytes \>1,500/mm3) 3. No extramedullary disease.

GroupValue95% CI
Dose Level 1: 12 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 2: 14 Gy Iodine-131 + BC8 Monoclonal Antibody1
Dose Level 3: 16 Gy Iodine-131 + BC8 Monoclonal Antibody1
Dose Level 4: 18 Gy Iodine-131 + BC8 Monoclonal Antibody1
Dose Level 5: 20 Gy Iodine-131 + BC8 Monoclonal Antibody1
Dose Level 6: 22 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 7: 24 Gy Iodine-131 + BC8 Monoclonal Antibody0
Dose Level 8: 26 Gy Iodine-131 + BC8 Monoclonal Antibody1

Adverse events — posted to ClinicalTrials.gov

Time frame: Serious adverse events and Other (not including serious adverse events) were monitored and recorded from the time of first exposure to the investigational product (i.e. Iodine 131 + BC8 mAB) through day +100 post-transplant or through patient discharge from the Seattle Cancer Care Alliance (SCCA) system to the patient's primary physician. All-Cause Mortality was monitored/assessed for up to 2 years or through participant survival after completing the study regimen and transplant.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Dose Level 1: 12 Gy Iodine-131 + BC8 Monoclonal Antibody
Serious: 1/1 (100%)
Deaths: 1/1
Dose Level 2: 14 Gy Iodine-131 + BC8 Monoclonal Antibody
Serious: 1/1 (100%)
Deaths: 0/1
Dose Level 3: 16 Gy Iodine-131 + BC8 Monoclonal Antibody
Serious: 4/5 (80%)
Deaths: 5/5
Dose Level 4: 18 Gy Iodine-131 + BC8 Monoclonal Antibody
Serious: 1/1 (100%)
Deaths: 0/1
Dose Level 5: 20 Gy Iodine-131 + BC8 Monoclonal Antibody
Serious: 0/1 (0%)
Deaths: 0/1
Dose Level 6: 22 Gy Iodine-131 + BC8 Monoclonal Antibody
Serious: 2/2 (100%)
Deaths: 2/2
Dose Level 7: 24 Gy Iodine-131 + BC8 Monoclonal Antibody
Serious: 5/7 (71%)
Deaths: 5/7
Dose Level 8: 26 Gy Iodine-131 + BC8 Monoclonal Antibody
Serious: 7/7 (100%)
Deaths: 7/7

Serious adverse events (52 terms)

ReactionSystemDose Level 1: 12 Gy Iodine…Dose Level 2: 14 Gy Iodine…Dose Level 3: 16 Gy Iodine…Dose Level 4: 18 Gy Iodine…Dose Level 5: 20 Gy Iodine…Dose Level 6: 22 Gy Iodine…Dose Level 7: 24 Gy Iodine…Dose Level 8: 26 Gy Iodine…
DiarrheaGastrointestinal disorders
NauseaGastrointestinal disorders
Febrile neutropenia (fever of unknown origin without clinically or microbiologically documented infeInfections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils BloodInfections and infestations
Supraventricular and nodal arrhythmiaCardiac disorders
AsystoleCardiac disorders
Ventricular ArrythmiaCardiac disorders
HypotensionCardiac disorders
Skin GVHDSkin and subcutaneous tissue disorders
GastritisGastrointestinal disorders
Mucositis/stomatitis (clinical exam) AnusGastrointestinal disorders
Mucositis/stomatitis (clinical exam) Oral cavityGastrointestinal disorders
VomitingGastrointestinal disorders
Hemorrhage, GU BladderRenal and urinary disorders
Hemorrhage, GU UrethraRenal and urinary disorders
Splenic HemorrhageGeneral disorders
Diffuse Alveolar HemorrhageRespiratory, thoracic and mediastinal disorders
GI BleedGastrointestinal disorders
Hepatobiliary/Pancreas - Other (Specify, Liver)Hepatobiliary disorders
CMV ReactivationInfections and infestations
CMV GastritisInfections and infestations
Infection - Other (Specify, Blood)Infections and infestations
Infection - Other (Specify, Salivary gland)Infections and infestations
Infection with grade 3 or 4 neutrophilsInfections and infestations
Upper Respiratory Infection (Pneumonia)Infections and infestations
Other adverse events (146 terms — click to expand)

ReactionSystemDose Level 1: 12 Gy Iodine…Dose Level 2: 14 Gy Iodine…Dose Level 3: 16 Gy Iodine…Dose Level 4: 18 Gy Iodine…Dose Level 5: 20 Gy Iodine…Dose Level 6: 22 Gy Iodine…Dose Level 7: 24 Gy Iodine…Dose Level 8: 26 Gy Iodine…
FatigueGeneral disorders
AnorexiaGastrointestinal disorders
DiarrheaGastrointestinal disorders
NauseaGastrointestinal disorders
MucositisGastrointestinal disorders
Epistaxis (HEMORRHAGE/BLEEDING)General disorders
Strep. ViridansInfections and infestations
CreatinineMetabolism and nutrition disorders
Pain - HeadacheGeneral disorders
CoughRespiratory, thoracic and mediastinal disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
Allergic ReactionImmune system disorders
VomitingGastrointestinal disorders
Coag Negative StaphInfections and infestations
ParainfluenzaInfections and infestations
Edema - LimbBlood and lymphatic system disorders
ALT, SGPT (serum glutamic pyruvic transaminase)Metabolism and nutrition disorders
AST, SGOT(serum glutamic oxaloacetic transaminase)Metabolism and nutrition disorders
Muscle WeaknessMusculoskeletal and connective tissue disorders
Pain - AbdomenGeneral disorders
HypertensionCardiac disorders
HypotensionCardiac disorders
RigorsGeneral disorders
HypothyroidismEndocrine disorders
Dry MouthGastrointestinal disorders
Hemorrhage-PetechaieGeneral disorders
C. DifficileInfections and infestations
CMV ReactivationInfections and infestations
Enterobacter faecalisInfections and infestations
Febrile NeutropeniaInfections and infestations
Bilirubin (hyperbilirubinemia)Metabolism and nutrition disorders
HyperglycemiaMetabolism and nutrition disorders
Neuropathy: sensoryNervous system disorders
Pain - AbdomenGeneral disorders
Pain - UrethraGeneral disorders
Joint PainGeneral disorders
AtelectasisRespiratory, thoracic and mediastinal disorders
NeutropeniaBlood and lymphatic system disorders
Platelets decreasedBlood and lymphatic system disorders
WBC decreasedBlood and lymphatic system disorders

Most-reported serious reactions: Diarrhea, Nausea, Febrile neutropenia (fever of unknown origin without clinically or microbiologically documented infe, Infection with normal ANC or Grade 1 or 2 neutrophils Blood, Supraventricular and nodal arrhythmia, Asystole, Ventricular Arrythmia, Hypotension.

Data from ClinicalTrials.gov NCT00589316 adverse events section.

Sponsor's own description

This phase I trial studies the side effects and best dose of iodine I 131monoclonal antibody BC8 when given together with fludarabine phosphate, cyclophosphamide, total-body irradiation, and donor bone marrow transplant, and to see how well they work in treating patients with acute myeloid leukemia or acute lymphoblastic leukemia that has spread to nearby or other places in the body (advanced), or high-risk myelodysplastic syndrome. Giving chemotherapy drugs, such as fludarabine phosphate and cyclophosphamide, and total-body irradiation before a donor 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. Also, radiolabeled monoclonal antibodies, such as iodine I 131 monoclonal antibody 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 cyclophosphamide together with mycophenolate mofetil and tacrolimus after the transplant may stop this from happening. Giving a radiolabeled monoclonal antibody together with donor stem cell transplant, fludarabine phosphate, cyclophosphamide, mycophenolate mofetil, and tacrolimus may be an effective treatment for advanced acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndromes.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Antibody Therapies for Acute Myeloid Leukemia: Unconjugated, Toxin-Conjugated, Radio-Conjugated and Multivalent Formats.
    Williams BA, Law A, Hunyadkurti J, Desilets S, et al · · 2019 · cited 43× · PMID 31434267 · DOI 10.3390/jcm8081261
  2. Targeted Radiation Delivery before Haploidentical HCT for High-risk Leukemia or MDS Patients Yields Long-term Survivors.
    Orozco JJ, Vo PT, Gooley TA, Haaf RL, et al · · 2024 · cited 3× · PMID 37939122 · DOI 10.1158/1078-0432.ccr-23-1200
  3. Emerging strategies and novel therapeutic targets in acute myeloid leukemia: current advances and future directions.
    Cao L, Wang Z, Cui Y, Li Y, et al · · 2025 · cited 1× · PMID 41088434 · DOI 10.1186/s40364-025-00839-2

Verify or expand the search:

Other trials of Allogeneic Bone Marrow Transplantation

Trials testing the same drug.

Other recruiting trials for Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome

Currently open trials in the same condition.

Other Fred Hutchinson Cancer Center trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT00589316.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing