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

NCT00988715 | Completed Phase 1 DMC

• 4 other identifiers: 2309.00NCI-2009-01294P01CA044991P30CA015704
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Chronic Myelomonocytic Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Cytopenia With Multilineage Dysplasia; Refractory Cytopenia With Multilineage Dysplasia and Ringed Sideroblasts; Secondary Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (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%.

  Within 100 days post-transplant

Secondary Outcomes (4)

• Rates of engraftment, chimerism, and non-relapse mortality

  Days 28

• Rates of engraftment, chimerism, and non-relapse mortality

  Day 84

• Rate of grades III-IV acute GVHD

  At day +100

• Achievement and duration of response

  Up to 24 months

Study Arms (1)

Treatment (PRIT, transplant)

EXPERIMENTAL

Patients 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.

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

Interventions

Pretargeted Radioimmunotherapy BIOLOGICAL

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

Treatment (PRIT, transplant)

Cyclosporine DRUG

Given IV

Also known as: 27-400, CsA, Neoral, OL 27-400, Sandimmun

Treatment (PRIT, transplant)

Mycophenolate Mofetil DRUG

Given PO

Also known as: Cellcept, MMF

Treatment (PRIT, transplant)

Total-Body Irradiation RADIATION

Undergo total-body irradiation

Also known as: TBI, Total Body Irradiation, Whole-Body Irradiation

Treatment (PRIT, transplant)

Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo peripheral blood stem cell transplant

Also known as: Non-myeloablative allogeneic transplant, Nonmyeloablative Stem Cell Transplantation, NST

Treatment (PRIT, transplant)

Peripheral Blood Stem Cell Transplantation PROCEDURE

Undergo peripheral blood stem cell transplant

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

Treatment (PRIT, transplant)

Fludarabine Phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, Beneflur, SH T 586

Treatment (PRIT, transplant)

Pharmacological Study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (PRIT, transplant)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (PRIT, transplant)

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 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

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

Study Sites (1)

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

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

Interventions

Cyclosporine; Cyclosporins; Mycophenolic Acid; Whole-Body Irradiation; Peripheral Blood Stem Cell Transplantation; fludarabine phosphate

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; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Radiotherapy; Therapeutics; Investigative Techniques; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Transplantation; Surgical Procedures, Operative

Study Officials

• Brenda Sandmaier

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2009
• First Posted: October 2, 2009
• Study Start: April 21, 2010
• Primary Completion: January 1, 2015
• Last Updated: August 30, 2017

Record last verified: 2017-08

Locations

US (1)