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

NCT00589316 | Terminated Phase 1 Results

• 5 other identifiers: 2186.00NCI-2010-004042186.00pP01CA044991RG1707019
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; CD45-Positive Neoplastic Cells Present; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndrome; Refractory Anemia With Excess Blasts; Refractory Anemia With Ring Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Refractory Cytopenia With Multilineage Dysplasia and Ring Sideroblasts

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Dose-limiting Toxicities (DLT) 30 Days After 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, the toxicity obtained would be manageable by clinical methods but may interfere with other therapies. Grade 3 Development of major clinical, chemical or laboratory abnormalities which represent maximum toxicities without being fatal. This grade of toxicity is designed to be the dose-limiting toxicity. Grade 4 Fatal

  Up to 30 days post-transplant

Secondary Outcomes (5)

• Number of Participants With Transplant-Related Mortality Within 100 Days After Transplant

  Up to 100 days post-transplant

• Participant Disease Response Within 90 Days After Transplant

  Up to 90 days after transplant

• Severity of Acute GVHD in Patients Who Completed the Study Treatment

  100 days after transplant

• Number of Participants With 100% Donor Chimerism at Day 84

  Day 84 after transplant

• Two-Year Disease-free Survival of Study Participants Who Completed the Study Regimen

  2 years post-transplant

Study Arms (1)

Treatment (chemo, TBI, transplant, immunosuppression)

EXPERIMENTAL

RADIOIMMUNOTHERAPY: Patients receive therapeutic iodine I 131 monoclonal antibody BC8 via central line on day -14. NONMYELOABLATIVE CONDITIONING: Patients receive FLU IV over 30 minutes on days -6 to -2 and CY IV over 1 hour on days -6 and -5. Patients undergo TBI on day -1. TRANSPLANTATION: Patients undergo allogeneic bone marrow transplantation on day 0. POST-TRANSPLATATION IMMUNOSUPPRESSION: Patients receive CY IV over 1-2 hours on day 3, MMF IV or PO TID on days 4 to 35, and tacrolimus IV over 1-2 hours or PO on days 4 to 180 with taper on day 84.

Procedure: Allogeneic Bone Marrow Transplantation; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Radiation: Iodine I 131 Monoclonal Antibody BC8; Other: Laboratory Biomarker Analysis; Drug: Mycophenolate Mofetil; Drug: Tacrolimus; Radiation: Total-Body Irradiation

Interventions

Allogeneic Bone Marrow Transplantation PROCEDURE

Given via central line

Also known as: Allo BMT, Allogeneic BMT

Treatment (chemo, TBI, transplant, immunosuppression)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (chemo, TBI, transplant, immunosuppression)

Fludarabine Phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586

Treatment (chemo, TBI, transplant, immunosuppression)

Iodine I 131 Monoclonal Antibody BC8 RADIATION

Given IV (dosimetry dose) or via central line (therapeutic dose)

Also known as: I 131 MOAB BC8, I 131 Monoclonal Antibody BC8, iodine I 131 MOAB BC8, Iomab-B, MOAB BC8, iodine I 131, monoclonal antibody BC8, iodine I 131

Treatment (chemo, TBI, transplant, immunosuppression)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (chemo, TBI, transplant, immunosuppression)

Mycophenolate Mofetil DRUG

Given IV or PO

Also known as: Cellcept, MMF

Treatment (chemo, TBI, transplant, immunosuppression)

Tacrolimus DRUG

Given IV or PO

Also known as: FK 506, Fujimycin, Hecoria, Prograf, Protopic

Treatment (chemo, TBI, transplant, immunosuppression)

Total-Body Irradiation RADIATION

Undergo TBI

Also known as: TOTAL BODY IRRADIATION, Whole-Body Irradiation

Treatment (chemo, TBI, transplant, immunosuppression)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 cluster of differentiation (CD)45-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)
• 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 a creatinine clearance greater than 50/ml per minute by the following formula (test must be performed within 28 days prior to registration):
• Creatinine clearance (CrCl) = (140-age) (Wt in Kg) x 0.85 (female) OR 1.0 (male)/72 x serum Cr
• Bilirubin \< 2 times the upper limit of normal
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 2 times the upper limit of normal
• 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 related donor who is identical for one human leukocyte antigen (HLA) haplotype and mismatched at the HLA-A, -B or class II, DR beta 1 (DRB1) loci of the unshared haplotype with the exception of single HLA-A, -B or DRB1 mismatches
• DONOR: Related donor who is identical for one HLA haplotype and mismatched at the HLA-A, -B, or DRB1 loci of the unshared haplotype with the exception of single HLA-A, -B, or DRB1 mismatches

You may not qualify if:

• Circulating antibody against mouse immunoglobulin (HAMA)
• Prior radiation to maximally tolerated levels to any critical normal organ
• Cross-match positive with donor
• 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 capacity of carbon monoxide (DLCO) \< 35% and/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
• Patients who are known seropositive for human immunodeficiency virus (HIV)
• Perceived inability to tolerate diagnostic or therapeutic procedures, particularly treatment in radiation isolation
• Central nervous system (CNS) involvement with disease refractory to intrathecal chemotherapy and/or standard cranial-spinal radiotherapy
• Women of childbearing potential who are pregnant (beta-human chorionic gonadotropin positive \[b-HCG+\]) 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• Orozco JJ, Vo PT, Gooley TA, Haaf RL, Lundberg SJ, Hamlin DK, Wilbur DS, Matesan MC, Fisher DR, Gopal AK, Green DJ, Pagel JM, Sandmaier BM. Targeted Radiation Delivery before Haploidentical HCT for High-risk Leukemia or MDS Patients Yields Long-term Survivors. Clin Cancer Res. 2024 Jan 17;30(2):274-282. doi: 10.1158/1078-0432.CCR-23-1200.

  PMID: 37939122 DERIVED

MeSH Terms

Conditions

Leukemia, Myelomonocytic, Chronic; Anemia, Refractory, with Excess of Blasts

Interventions

Cyclophosphamide; fludarabine phosphate; Iodine-131; Mycophenolic Acid; Tacrolimus; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Anemia, Refractory; Anemia; Myelodysplastic Syndromes

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Macrolides; Lactones; Radiotherapy; Therapeutics; Investigative Techniques

Limitations and Caveats

Study accrual has been lower (i.e., 26 total) than the planned target accrual of 50 due to the prioritization of other clinical trials using an alternative radiometal (yttrium-90 \[90Y\]) and antibody construct (BC8-DOTA).

Results Point of Contact

• Title: Johnnie Orozco, MD, PhD
• Organization: Fred Hutchinson Cancer Center

jorozco@fredhutch.org

(206) 667-4102

Study Officials

• Johnnie Orozco

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: January 3, 2008
• First Posted: January 9, 2008
• Study Start: October 5, 2007
• Primary Completion: October 1, 2016
• Study Completion: October 1, 2021
• Last Updated: February 9, 2023
• Results First Posted: February 9, 2023

Record last verified: 2023-01

Locations

US (1)