Alemtuzumab, Fludarabine, and Busulfan Followed By Donor Stem Cell Transplant in Treating Young Patients With Hematologic Disorders

NCT00301834 | Completed Phase 2 Results

• 4 other identifiers: CDR0000462406UCSF-04152UCSF-00452UCSF-H411-25738-02
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 2

Brief Summary

RATIONALE: Monoclonal antibodies, such as alemtuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as fludarabine and busulfan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. A peripheral stem cell, bone marrow , or umbilical cord blood transplant may be able to replace blood-forming cells that were destroyed by chemotherapy. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine together with methotrexate and methylprednisolone may stop this from happening. PURPOSE: This phase II trial is studying how well giving alemtuzumab together with fludarabine and busulfan works when given before donor stem cell transplant in treating young patients with hematologic disorders.

Conditions

Congenital Amegakaryocytic Thrombocytopenia; Diamond-blackfan Anemia; Leukemia; Myelodysplastic Syndromes; Severe Congenital Neutropenia

Keywords

de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; childhood acute myeloid leukemia in remission; childhood chronic myelogenous leukemia; congenital amegakaryocytic thrombocytopenia; Diamond-Blackfan anemia; severe congenital neutropenia; secondary acute myeloid leukemia; chronic phase chronic myelogenous leukemia; childhood myelodysplastic syndromes

Outcome Measures

Primary Outcomes (1)

• Number of Participants Achieving Durable Engraftment (Presence of Donor Cells) at 6 Weeks Post Transplantation

  Peripheral blood chimerism studies were performed by quantitative real time polymerase chain reaction (qPCR) evaluation of differential short tandem repeat DNA sequences

  6 weeks post-transplant

Secondary Outcomes (4)

• Treatment-related Mortality at 100 Days and 1 Year Post Transplantation

  100 days and 1 year

• Toxicity Grade ≥ 3 From Start of Conditioning Through the First Year Post Transplantation

  1 year post-transplantation

• Cytomegalovirus (CMV) Viral Infection and Disease Symptoms

  Up to one year post-transplant

• Disease-free Survival With Correction of Disease at One Year Post Transplantation

  1 year post-transplantation

Study Arms (1)

Single arm - conditioning and transplant

EXPERIMENTAL

Alemtuzumab 0.5 mg/kg (maximum 15 mg) daily for 3 days; Busulfan i.v. every 6 hours from day -9 to day -6 for 16 total doses; Fludarabine phosphate from day -5 for 4 days at 1.3 mg/kg (if patient was less than 12 kg) or 40 mg/m\*2 per dose; Cyclosporine continuous infusion 3 mg/kg/Day beginning day -1 for GVHD prophylaxis; Methotrexate at 15 mg/m\*2 on day +1, 10 mg/m\*2 on days +3, +6, and (only for MUDs) day +11 also for GVHD prophylaxis; Methylprednisolone only as required for GVHD prophylaxis; allogeneic bone marrow transplantation or allogeneic hematopoietic stem cell transplantation or peripheral blood stem cell transplantation or umbilical cord blood transplantation.

Biological: alemtuzumab; Drug: busulfan; Drug: cyclosporine; Drug: fludarabine phosphate; Drug: methotrexate; Drug: methylprednisolone; Procedure: allogeneic bone marrow transplantation; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation; Procedure: umbilical cord blood transplantation

Interventions

alemtuzumab BIOLOGICAL

Single arm - conditioning and transplant

busulfan DRUG

Single arm - conditioning and transplant

cyclosporine DRUG

Single arm - conditioning and transplant

fludarabine phosphate DRUG

Single arm - conditioning and transplant

methotrexate DRUG

Single arm - conditioning and transplant

methylprednisolone DRUG

Single arm - conditioning and transplant

allogeneic bone marrow transplantation PROCEDURE

Single arm - conditioning and transplant

allogeneic hematopoietic stem cell transplantation PROCEDURE

Single arm - conditioning and transplant

peripheral blood stem cell transplantation PROCEDURE

Single arm - conditioning and transplant

umbilical cord blood transplantation PROCEDURE

Single arm - conditioning and transplant

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

DISEASE CHARACTERISTICS: * Diagnosis of 1 of the following hematologic conditions: * Aplastic anemia with marrow aplasia, meeting all of the following criteria: * Absolute neutrophil count \< 500/mm\^3 * Platelet and/or red cell transfusion dependent * Chronic aplastic anemia, meeting all of the following criteria: * Transfusion dependent * Unresponsive to immunosuppressive therapy * Alternative matched unrelated donor has been identified * Congenital marrow failure syndrome, including any of the following (with closely matched related or unrelated donor): * Primary red cell aplasia (Diamond-Blackfan syndrome) * Congenital neutropenia (Kostmann's syndrome) * Amegakaryocytic thrombocytopenia * Congenital dyserythropoietic anemias * Other severe acquired cytopenias in which a transplantation using a combined busulfan/cyclophosphamide conditioning regimen is indicated * Hemoglobinopathy (with closely matched related or unrelated donor) * β-thalassemia major * Sickle cell anemia * Hemoglobin E/β-thalassemia * Severe immunodeficiency disease * Chediak-Higashi disease * Wiskott-Aldrich syndrome * Combined immunodeficiency disease (Nezelof's) * Hyper immunoglobulin M (IgM) syndrome * Bare lymphocyte syndrome * Chronic granulomatous disease * Familial erythrohemophagocytic lymphohistiocytosis * Other stem cell defects (e.g., osteopetrosis) * Severe immune dysregulation/autoimmune disorders * Achieved a transient response to prior immunosuppressive therapy * Chronic myelogenous leukemia * Disease in first chronic phase * Acute myeloid leukemia * Disease in first remission * Myelodysplastic syndromes * Inborn errors of metabolism * Histiocytosis * No severe combined immunodeficiency disease * Matched related or unrelated donor available by high resolution DNA typing * Related donor, meeting both of the following criteria: * Matched at both human leukocyte antigen (HLA)-Drβ1 alleles * No more than 1 mismatch at the 4 HLA-A and -B alleles * Unrelated donor, meeting 1 of the following criteria: * Marrow matched at both HLA-Drβ1 alleles AND no more than 1 mismatch at the 4 HLA-A and -B alleles * Umbilical cord blood matched at 5/6 HLA-A, -B, and -DRβ1 alleles with at least 1 -DRβ1 match AND there are ≥ 3x10\^5 CD34+ (Cluster of differentiation 34-positive) cells per kg body weight of recipient available at the time of cryopreservation PATIENT CHARACTERISTICS: * Cardiac ejection fraction ≥ 27% * Creatinine clearance ≥ 50 mL/min by 24-hour urine collection or glomerular filtration rate * DLCO (diffusion capacity of lung for carbon monoxide) ≥ 50% of predicted (corrected for anemia/lung volume) PRIOR CONCURRENT THERAPY: * No prior transplantation for leukemia from which patient remains engrafted and alemtuzumab is not needed as part of the conditioning regimen

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

Madison, Wisconsin, 53792-6164, United States

Location

MeSH Terms

Conditions

Congenital amegakaryocytic thrombocytopenia; Anemia, Diamond-Blackfan; Leukemia; Myelodysplastic Syndromes; Neutropenia, Severe Congenital, Autosomal Recessive 3; Leukemia, Myeloid, Chronic-Phase

Interventions

Alemtuzumab; Busulfan; Cyclosporine; fludarabine phosphate; Methotrexate; Methylprednisolone; Peripheral Blood Stem Cell Transplantation; Cord Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Anemia, Hypoplastic, Congenital; Anemia, Aplastic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Red-Cell Aplasia, Pure; Congenital Bone Marrow Failure Syndromes; Bone Marrow Failure Disorders; Bone Marrow Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neoplasms by Histologic Type; Neoplasms; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Myeloproliferative Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Results Point of Contact

• Title: Dr. Morton Cowan
• Organization: University of California San Francisco

mcowan@peds.ucsf.edu

4154762188

Study Officials

• Morton J. Cowan, MD

  University of California, San Francisco

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2006
• First Posted: March 13, 2006
• Study Start: January 1, 2005
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2011
• Last Updated: September 28, 2017
• Results First Posted: May 16, 2013

Record last verified: 2017-08

Locations

US (2)