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

NCT01300572 | Completed Phase 1 Results DMC

• 6 other identifiers: 2468.00NCI-2011-001502468.00A2468P01CA044991P30CA015704
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Secondary Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (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.

  Within the first 30 days following transplant

Secondary Outcomes (9)

• Achievement of Remission

  4 weeks after transplant

• Disease-free Survival

  100 days after transplant

• Duration of Remission

  1 year

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

  Approximately day -20 to day -12 prior to transplant

• Overall Survival

  Up to 5 years

Study Arms (1)

Y-90-BC8 & Allogeneic Transplant

EXPERIMENTAL

PREPARATIVE 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.

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

Interventions

Allogeneic Bone Marrow Transplantation PROCEDURE

Undergo allogeneic bone marrow transplant

Also known as: Allo BMT, Allogeneic BMT

Y-90-BC8 & Allogeneic Transplant

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo allogeneic PBSC or bone marrow transplant

Also known as: allogeneic stem cell transplantation, HSC, HSCT

Y-90-BC8 & Allogeneic Transplant

Cyclosporine DRUG

Given PO or IV

Also known as: 27-400, Ciclosporin, CsA, Cyclosporin, Cyclosporin A, Gengraf, Neoral, OL 27-400, Sandimmun, Sandimmune, SangCya

Y-90-BC8 & Allogeneic Transplant

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

Y-90-BC8 & Allogeneic Transplant

Indium In 111 Anti-CD45 Monoclonal Antibody BC8 BIOLOGICAL

Given IV (dosimetric dose)

Also known as: In 111 MOAB BC8, In 111 Monoclonal Antibody BC8, Indium In 111 Monoclonal Antibody BC8, monoclonal antibody BC8, indium In 111

Y-90-BC8 & Allogeneic Transplant

Laboratory Biomarker Analysis OTHER

Correlative studies

Y-90-BC8 & Allogeneic Transplant

Mycophenolate Mofetil DRUG

Given PO or IV

Also known as: Cellcept, MMF

Y-90-BC8 & Allogeneic Transplant

Peripheral Blood Stem Cell Transplantation PROCEDURE

Undergo allogeneic PBSC transplant

Also known as: PBPC transplantation, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell Transplantation

Y-90-BC8 & Allogeneic Transplant

Pharmacological Study OTHER

Correlative studies

Y-90-BC8 & Allogeneic Transplant

Total-Body Irradiation RADIATION

Undergo TBI

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

Y-90-BC8 & Allogeneic Transplant

Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8 RADIATION

Given via central line (therapeutic dose)

Also known as: 90Y Anti-CD45 MoAb BC8

Y-90-BC8 & Allogeneic Transplant

Eligibility Criteria

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

You may qualify if:

• 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)
• 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:

You may not qualify if:

• 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
• 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

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)

• 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.

  PMID: 31582553 DERIVED

MeSH Terms

Conditions

Leukemia, Myelomonocytic, Chronic; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Anemia, Refractory, with Excess of Blasts

Interventions

Cyclosporine; Cyclosporins; fludarabine phosphate; Indium; Mycophenolic Acid; Peripheral Blood Stem Cell Transplantation; 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; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Anemia, Refractory; Anemia; Myelodysplastic Syndromes

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Metals, Heavy; Elements; Inorganic Chemicals; Metals; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Radiotherapy; Investigative Techniques

Limitations and Caveats

The highest dose achieved was 28 Gy but none of the patients experienced a DLT. Thus, the MTD was not reached.

Results Point of Contact

• Title: Brenda Sandmaier, MD
• Organization: Fred Hutchinson Cancer Research Center

bsandmai@fredhtuch.org

(206) 667-4961

Study Officials

• Brenda Sandmaier

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: Principal Investigator

Study Record Dates

• First Submitted: February 15, 2011
• First Posted: February 21, 2011
• Study Start: January 1, 2012
• Primary Completion: October 29, 2017
• Study Completion: November 22, 2019
• Last Updated: December 10, 2019
• Results First Posted: January 25, 2019

Record last verified: 2019-12

Locations

US (1)