Donor Stem Cell Transplant in Treating Patients With Relapsed Hematologic Malignancies or Secondary Myelodysplasia Previously Treated With High-Dose Chemotherapy and Autologous Stem Cell Transplant

NCT01118013 | Terminated Phase 2 Results

• 2 other identifiers: CALGB-100601CDR0000667954
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 10

Brief Summary

RATIONALE: Giving chemotherapy, such as busulfan and fludarabine phosphate, before a peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving methotrexate, tacrolimus, and antithymocyte globulin before and after the transplant may stop this from happening. Once the donated stem cells begin working, the patient's immune system may see the remaining cancer cells as not belonging in the patient's body and destroy them (called graft-versus-tumor effect). Giving an infusion of the donor's white blood cells (donor lymphocyte infusion) may boost this effect. PURPOSE: This phase II trial is studying how well donor stem cell transplant works in treating patients with relapsed hematologic malignancies or secondary myelodysplasia previously treated with high-dose chemotherapy and autologous stem cell transplant .

Conditions

Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms

Keywords

adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with t(15;17)(q22;q12); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with t(8;21)(q22;q22); juvenile myelomonocytic leukemia; prolymphocytic leukemia; recurrent adult acute myeloid leukemia; recurrent adult T-cell leukemia/lymphoma; recurrent childhood acute myeloid leukemia; refractory chronic lymphocytic leukemia; recurrent adult Hodgkin lymphoma; recurrent adult Burkitt lymphoma; recurrent adult diffuse large cell lymphoma; recurrent adult diffuse mixed cell lymphoma; recurrent adult diffuse small cleaved cell lymphoma; recurrent adult grade III lymphomatoid granulomatosis; recurrent adult immunoblastic large cell lymphoma; recurrent adult lymphoblastic lymphoma; recurrent childhood grade III lymphomatoid granulomatosis; recurrent childhood large cell lymphoma; recurrent childhood lymphoblastic lymphoma; recurrent childhood small noncleaved cell lymphoma; recurrent cutaneous T-cell non-Hodgkin lymphoma; recurrent mycosis fungoides/Sezary syndrome; recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma; recurrent mantle cell lymphoma; recurrent marginal zone lymphoma; recurrent small lymphocytic lymphoma; recurrent/refractory childhood Hodgkin lymphoma; childhood diffuse large cell lymphoma; childhood grade III lymphomatoid granulomatosis; childhood immunoblastic large cell lymphoma; childhood nasal type extranodal NK/T-cell lymphoma; post-transplant lymphoproliferative disorder; stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma; refractory multiple myeloma; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; childhood myelodysplastic syndromes; recurrent childhood anaplastic large cell lymphoma; adult acute myelomonocytic leukemia (M4); childhood acute myelomonocytic leukemia (M4); adult acute minimally differentiated myeloid leukemia (M0); childhood acute minimally differentiated myeloid leukemia (M0); adult acute myeloblastic leukemia without maturation (M1); childhood acute myeloblastic leukemia without maturation (M1); adult acute myeloblastic leukemia with maturation (M2); childhood acute myeloblastic leukemia with maturation (M2); adult acute promyelocytic leukemia (M3); childhood acute promyelocytic leukemia (M3); adult acute monoblastic leukemia (M5a); adult acute monocytic leukemia (M5b); childhood acute monoblastic leukemia (M5a); childhood acute monocytic leukemia (M5b); adult erythroleukemia (M6a); adult pure erythroid leukemia (M6b); childhood acute erythroleukemia (M6); adult acute megakaryoblastic leukemia (M7); childhood acute megakaryocytic leukemia (M7); childhood Burkitt lymphoma; atypical chronic myeloid leukemia, BCR-ABL1 negative; chronic myelomonocytic leukemia; cutaneous B-cell non-Hodgkin lymphoma; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone B-cell lymphoma; splenic marginal zone lymphoma; myelodysplastic/myeloproliferative neoplasm, unclassifiable

Outcome Measures

Primary Outcomes (2)

• Event-free Survival (EFS)

  EFS was defined as the date of transplant to date of progression or develop myelodysplasia after autologous transplant. EFS was estimated using the Kaplan Meier method.

  Duration of study (up to 5.5 years)

• Comparison of EFS Distribution to That of CALGB-100002

  EFS distributions between CALGB-100002 and this study will be compared using the two-sample log-rank test.

  2 years

Secondary Outcomes (3)

• Complete Response Rate

  Up to 5.5 years

• Overall Survival

  Up to 5.5 years

• Rate of Opportunistic Infections

  1 year post transplant

Study Arms (1)

Treatment

EXPERIMENTAL

Matched-unrelated donor: Patients receive antithymocyte globulin, tacrolimus, and methotrexate as in HLA-identical donor regimen. Patients also receive oral mycophenolate mofetil twice daily on days 0 to 60. Allogeneic Stem Cell Transplantation: Patients undergo allogeneic peripheral blood stem cell transplantation on days 0 and 1. Patients then receive filgrastim subcutaneously daily beginning on day 7 and continuing until blood counts recover. Donor Lymphocyte Infusion (DLI): After day 180 (or day 210 for patients without an HLA-identical donor), patients with stable or progressive disease and no active GVHD may receive up to 3 DLIs every 8 weeks. Blood samples are collected at baseline and then periodically during study therapy for pharmacokinetic studies. After completion of study therapy, patients are followed up every 3 months for 2 years and then every 6 months for up to 5½ years.

Biological: anti-thymocyte globulin; Biological: donor lymphocytes; Biological: filgrastim; Biological: therapeutic allogeneic lymphocytes; Drug: busulfan; Drug: fludarabine phosphate; Drug: methotrexate; Drug: mycophenolate mofetil; Drug: tacrolimus; Other: reduced-intensity transplant conditioning procedure; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation

Interventions

anti-thymocyte globulin BIOLOGICAL

Treatment

donor lymphocytes BIOLOGICAL

Treatment

filgrastim BIOLOGICAL

Treatment

therapeutic allogeneic lymphocytes BIOLOGICAL

Treatment

busulfan DRUG

Treatment

fludarabine phosphate DRUG

Treatment

methotrexate DRUG

Treatment

mycophenolate mofetil DRUG

Treatment

tacrolimus DRUG

Treatment

reduced-intensity transplant conditioning procedure OTHER

Treatment

allogeneic hematopoietic stem cell transplantation PROCEDURE

Treatment

peripheral blood stem cell transplantation PROCEDURE

Treatment

Eligibility Criteria

• Age: Up to 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically confirmed hematologic malignancies: * Chronic lymphocytic leukemia (CLL) or prolymphocytic leukemia (PLL) * Absolute lymphocytosis of \> 5,000/μL * Lymphocytes must appear morphologically mature with \< 55% prolymphocytes (CLL) * Patients with \> 55% prolymphocytes are considered as having PLL * Lymphocyte phenotype with expression of CD20, CD19, and CD5 (CLL) * Non-Hodgkin lymphoma * Any WHO classification of histologic subtype * Core biopsies acceptable for primary diagnosis and immunophenotyping * Bone marrow biopsies as sole means of diagnosis not allowed for follicular lymphoma * Hodgkin lymphoma * Any WHO classification of histologic subtype * Core biopsies acceptable for primary diagnosis and immunophenotyping * Bone marrow biopsy is required * Multiple myeloma * Patients must have active disease requiring treatment (Durie-Salmon stage I-III) * Acute myeloid leukemia * Must have \< 10% bone marrow blasts and no circulating blasts * Myelodysplastic syndrome (MDS) * MDS as define by WHO criteria * Must have \< 10% marrow blasts * Relapsed or progressive disease or myelodysplasia ≥ 6 months after prior high-dose chemotherapy with autologous hematopoietic cell support * Prior syngeneic transplantation allowed * Healthy donor meeting one of the following criteria: * HLA-identical sibling (6/6) * Serologic typing for class I (A, B) and molecular typing for class II (DRB1) required * 8/8 matched-unrelated donor * Molecular identity at HLA A, B, C, and DRB1 by high-resolution typing required * No syngeneic donors PATIENT CHARACTERISTICS: * Creatinine clearance ≥ 40 mL/min * Total bilirubin ≤ 2 mg/dL * AST ≤ 3 times upper limit of normal * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * DLCO ≥ 40% with no symptomatic pulmonary disease * LVEF ≥ 30% by MUGA or ECHO * No uncontrolled diabetes mellitus or active serious infection * No known hypersensitivity to E.coli-derived products * No HIV infection PRIOR CONCURRENT THERAPY: * See Disease Characteristics * At least 4 weeks should elapse between prior standard cytotoxic chemotherapy, radiation therapy, or surgery and the planned start of the preparative regimen on day -7

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

Sponsors & Collaborators

• Alliance for Clinical Trials in Oncology: lead
• National Cancer Institute (NCI): collaborator

Study Sites (10)

Tunnell Cancer Center at Beebe Medical Center

Lewes, Delaware, 19958, United States

Location

CCOP - Christiana Care Health Services

Newark, Delaware, 19713, United States

Location

Florida Hospital Cancer Institute at Florida Hospital Orlando

Orlando, Florida, 32803-1273, United States

Location

Greenebaum Cancer Center at University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Union Hospital of Cecil County

Elkton MD, Maryland, 21921, United States

Location

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

St Louis, Missouri, 63110, United States

Location

Cancer Institute of New Jersey at Cooper - Voorhees

Voorhees Township, New Jersey, 08043, United States

Location

New York Weill Cornell Cancer Center at Cornell University

New York, New York, 10021, United States

Location

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157-1096, United States

Location

Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210-1240, United States

Location

MeSH Terms

Conditions

Leukemia; Lymphoma; Lymphoproliferative Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Myelodysplastic Syndromes; Myelodysplastic-Myeloproliferative Diseases; Congenital Abnormalities; Leukemia, Myelomonocytic, Juvenile; Leukemia, Prolymphocytic; Leukemia, Myeloid, Acute; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell; Hodgkin Disease; Burkitt Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Lymphoma, Large-Cell, Immunoblastic; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Dendritic Cell Sarcoma, Interdigitating; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Sezary Syndrome; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Lymphoma, B-Cell, Marginal Zone; Recurrence; Lymphoma, Extranodal NK-T-Cell; Lymphoma, Large-Cell, Anaplastic; Leukemia, Myelomonocytic, Acute; Leukemia, Promyelocytic, Acute; Leukemia, Monocytic, Acute; Leukemia, Erythroblastic, Acute; Leukemia, Megakaryoblastic, Acute; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Leukemia, Myelomonocytic, Chronic; Myeloproliferative Disorders

Interventions

Antilymphocyte Serum; Filgrastim; Busulfan; fludarabine phosphate; Methotrexate; Mycophenolic Acid; Tacrolimus; Peripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Bone Marrow Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Leukemia, Myeloid; Leukemia, Lymphoid; Leukemia, B-Cell; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Histiocytic Disorders, Malignant; Histiocytosis; Lymphoma, T-Cell

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Macrolides; Lactones; 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: Asad Bashey, MD, PhD
• Organization: Blood and Marrow Transplant Group of Georgia

abashey@bmtga.com

Study Officials

• Asad Bashey, MD, PhD

  Blood and Marrow Transplant Group of Georgia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: 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: May 5, 2010
• First Posted: May 6, 2010
• Study Start: December 1, 2010
• Primary Completion: March 1, 2012
• Study Completion: August 1, 2013
• Last Updated: March 24, 2017
• Results First Posted: March 24, 2017

Record last verified: 2017-02

Locations

US (10)