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Monoclonal Antibody Therapy After Allogeneic Stem Cell Transplantation in Treating Patients With Persistent or Progressive Cancer
This study has been suspended.
First Received: May 6, 2003   Last Updated: May 12, 2009   History of Changes
Sponsors and Collaborators: University of California, San Diego
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00060372
  Purpose

RATIONALE: Monoclonal antibodies can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells.

PURPOSE: This phase I trial is studying how well monoclonal antibody therapy works after allogeneic stem cell transplantation in treating patients with persistent or progressive cancer.


Condition Intervention Phase
Breast Cancer
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Neuroblastoma
Ovarian Cancer
Testicular Germ Cell Tumor
Biological: ipilimumab
Biological: therapeutic allogeneic lymphocytes
Procedure: adjuvant therapy
Phase I

Study Type: Interventional
Study Design: Treatment
Official Title: CTLA-4 Blockade With MDX-010 To Induce Graft - Versus - Malignancy Effects Following Allogeneic Hematopoietic Stem Cell Transplantation

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Estimated Enrollment: 21
Study Start Date: April 2003
Estimated Primary Completion Date: February 2004 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • Determine the optimal safe dose, in terms of incidence of grade 3 or 4 graft-versus-host disease, of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody administered to patients with persistent or progressive malignancies after allogeneic hematopoietic stem cell transplantation.
  • Determine the pharmacokinetics of this drug in these patients.
  • Determine the best dosing regimen of this drug when administered with donor lymphocyte infusions in these patients.
  • Determine, preliminarily, the efficacy of this drug in these patients.

OUTLINE: This is a dose-escalation, multicenter study.

Patients receive anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) IV over 90 minutes.

Cohorts of 3-6 patients receive escalating doses of MDX-010 until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients with persistent or progressive disease at 60 days after MDX-010 administration and no evidence of graft-versus-host disease receive donor lymphocyte infusions every 60 days for a total of 3 infusions.

Patients are followed at 4, 5, 6, 9, and 12 months and then annually thereafter.

PROJECTED ACCRUAL: A total of 18-21 patients will be accrued for this study within 24-30 months.

  Eligibility

Ages Eligible for Study:   14 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of persistent or progressive hematologic malignancy or solid tumor after allogeneic hematopoietic stem cell transplantation (AHSCT)

    • Patients are eligible for study entry at any time between post-transplantation day 90 and 3 years after withdrawal of immunosuppressive therapy
  • The following malignancies are eligible:

    • Chronic myelogenous leukemia (CML) meeting the following criteria:

      • Cytogenetic progression or persistence as evidenced by 1 of the following:

        • Cytogenetic progression evidenced by an increase in the percentage of Philadelphia chromosome (Ph)1-positive metaphases (or Ph1-positive cells by fluorescent in situ hybridization) from complete cytogenetic response (CCR) (0% Ph1-positive cells) to partial response (PR) (1-34% Ph1-positive cells); PR to minor response (MR) (35-94% Ph1-positive cells); or MR to no response (95-100% Ph1-positive cells)
        • Cytogenetic persistence evidenced by any Ph1-positive metaphases in bone marrow after day 90 post-AHSCT
      • Resistance to imatinib mesylate, defined as disease progression (hematologic, cytogenetic, or molecular) during OR failure to respond to (i.e., lack of complete hematologic response after 3 months, lack of partial cytogenetic response after 6 months, or lack of complete cytogenetic response after 12 months) prior imatinib mesylate therapy
    • Acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) that meets any of the following criteria:

      • Hematologic relapse by standard criteria
      • Hematologic persistence evidenced by bone marrow blasts > 10% after day 30 post-AHSCT
    • Myelodysplastic syndromes that meet any of the following criteria:

      • Hematologic relapse by standard criteria
      • Cytogenetic relapse evidenced by recurrence of clonal abnormality in patients who achieved CCR after AHSCT
      • Hematologic persistence evidenced by cytopenias not attributable to other post-transplant causes accompanied by characteristic morphological changes more than 90 days after AHSCT
      • Cytogenetic persistence evidenced by persistence of clonal abnormality more than 90 days after AHSCT
    • Chronic lymphocytic leukemia that meets any of the following criteria:

      • Greater than 25% increase in absolute lymphocytosis of > 5,000/mm^3
      • Greater than 25% increase in measurable lymphadenopathy
      • Persistence of absolute lymphocytosis of > 5,000/mm^3 at day 90 or later after AHSCT
      • Persistence of lymphadenopathy of ≥ 3 cm in diameter at day 90 or later after AHSCT
    • Agressive non-Hodgkin's lymphoma (e.g., diffuse large cell lymphoma, lymphoblastic lymphoma, mantle cell lymphoma, or peripheral T cell lymphoma), Hodgkin's lymphoma, OR solid tumor that meets any of the following criteria:

      • Greater than 50% increase in measurable or evaluable disease
      • Persistence of measurable lesions > 3.0 cm in diameter at day 90 or later after AHSCT
      • Persistence of malignancy by biopsy or positron emission tomography scan unless there is clear evidence of progression
    • Multiple myeloma with demonstrated resistance to or intolerance of prior thalidomide and bortezomib unless these agents are contraindicated (e.g., due to peripheral neuropathy) and meeting any of the following criteria:

      • Greater than 25% increase in paraprotein band, abnormal quantitative immunoglobulin level, or urine protein excretion
      • Greater than 25% increase in percent of plasma cells in the bone marrow (if > 15%)
      • Presence of new lytic bone lesions
      • New extramedullary lesions OR ≥ 25% enlargement of existing extramedullary lesions
      • Persistence of paraprotein band, abnormally elevated quantitative immunoglobulin level, or bone marrow plasmacytosis > 15% for a period of at least 90 days after AHSCT
  • Measurable or evaluable disease

    • At least 1 bidimensionally measurable lesion ≥ 1.5 cm in diameter
    • Evaluable disease is defined as disease that is assessable for response (e.g., pleural effusion, elevated serum tumor)
    • Bone metastases that can be assessed by CT scan or MRI considered evaluable
    • Leukemia is considered evaluable disease
    • Patients who met criteria for persistence or progression with AML, ALL, CML, or aggressive NHL AND are currently in complete remission after reinduction therapy do not require measurable or evaluable disease to be eligible
  • At least 50% donor chimerism in the T-cell lineage OR full (≥ 90%) donor chimerism in unseparated blood on last assessment within 3 months before study entry

    • No evidence on consecutive testing of > 10% decline in T-cell chimerism beyond the error of the test

PATIENT CHARACTERISTICS:

Age

  • 14 and over

Performance status

  • ECOG 0-2

Life expectancy

  • More than 3 months

Hematopoietic

  • See Disease Characteristics
  • Absolute lymphocyte count > 250/mm^3

Hepatic

  • Bilirubin ≤ 2.0 mg/dL*
  • AST and ALT ≤ 3 times upper limit of normal*
  • Chronic hepatitis B or C infection allowed provided other hepatic function criteria are met NOTE: *Unless due to the malignancy

Renal

  • Creatinine ≤ 2.0 mg/dL (unless due to the malignancy)

Immunologic

  • No prior grade 3 or 4 acute graft-vs-host disease
  • No concurrent autoimmune diseases requiring the chronic use of immunosuppressive medications

    • Active connective tissue disease
    • CNS disease including multiple sclerosis or demyelinating disease
    • Inflammatory bowel disease
    • Autoimmune hepatitis
  • No ongoing serious infection
  • No known history of HIV

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for at least 4 months after study therapy
  • No other serious ongoing medical condition that would preclude study participation
  • No other malignancy within the past 5 years
  • No psychological or psychiatric condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • See Disease Characteristics
  • No prior anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010)

Chemotherapy

  • Not specified

Endocrine therapy

  • Not specified

Radiotherapy

  • Not specified

Surgery

  • Not specified

Other

  • At least 6 weeks since prior immunosuppressive agents
  • At least 2 weeks since prior imatinib mesylate
  • No concurrent imatinib mesylate
  • At least 6 weeks since prior and no concurrent immunosuppressive agents for clinically active graft-versus-host disease (GVHD) prophylaxis or treatment
  • No other concurrent investigational agents
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00060372

Locations
United States, California
Ida M. and Cecil H. Green Cancer Center at Scripps Clinic
La Jolla, California, United States, 92037-1027
Rebecca and John Moores UCSD Cancer Center
La Jolla, California, United States, 92093-0658
United States, Georgia
Blood and Marrow Transplant Group of Georgia
Atlanta, Georgia, United States, 30342
Northside Hospital Cancer Center
Atlanta, Georgia, United States, 30342-1611
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
University of California, San Diego
Investigators
Study Chair: Asad Bashey, MD, PhD Blood and Marrow Transplant Group of Georgia
  More Information

Additional Information:
Publications:
Study ID Numbers: CDR0000301644, UCSD-040749, NCI-6082
Study First Received: May 6, 2003
Last Updated: May 12, 2009
ClinicalTrials.gov Identifier: NCT00060372     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
relapsing chronic myelogenous leukemia
recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
previously treated myelodysplastic syndromes
refractory chronic lymphocytic leukemia
recurrent adult Hodgkin lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult Burkitt lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent grade 3 follicular lymphoma
recurrent mantle cell lymphoma
Philadelphia chromosome positive chronic myelogenous leukemia
refractory multiple myeloma
recurrent malignant testicular germ cell tumor
stage III malignant testicular germ cell tumor
disseminated neuroblastoma
recurrent neuroblastoma
stage II ovarian epithelial cancer
recurrent ovarian epithelial cancer
stage III ovarian epithelial cancer
stage IV ovarian epithelial cancer
recurrent ovarian germ cell tumor
stage IIIA breast cancer
stage IV breast cancer
ovarian choriocarcinoma
ovarian embryonal carcinoma
ovarian yolk sac tumor
ovarian immature teratoma

Study placed in the following topic categories:
Philadelphia Chromosome
Neuroectodermal Tumors, Primitive
Lymphoma, Mantle-Cell
Seminoma
Mantle Cell Lymphoma
Urogenital Neoplasms
Follicular Lymphoma
Acute Myelocytic Leukemia
Preleukemia
Hemorrhagic Disorders
Acute Myeloid Leukemia, Adult
Leukemia, Lymphocytic, Chronic, B-Cell
Neuroepithelioma
Ovarian Cancer
Hodgkin Disease
Breast Diseases
Immunoglobulins
Endocrine Gland Neoplasms
Lymphoma, Large B-Cell, Diffuse
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immunoproliferative Disorders
Testicular Cancer
Hematologic Diseases
Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
Blood Coagulation Disorders
Adjuvants, Immunologic
Genital Neoplasms, Female
Endocrine System Diseases
Breast Neoplasms
Testicular Neoplasms

Additional relevant MeSH terms:
Neuroectodermal Tumors, Primitive
Precancerous Conditions
Gonadal Disorders
Blood Protein Disorders
Neoplasms, Nerve Tissue
Urogenital Neoplasms
Paraproteinemias
Ovarian Diseases
Hemostatic Disorders
Neuroblastoma
Genital Diseases, Female
Leukemia
Preleukemia
Pathologic Processes
Hemorrhagic Disorders
Neoplasms by Site
Neoplasms, Germ Cell and Embryonal
Syndrome
Cardiovascular Diseases
Lymphoma
Breast Diseases
Endocrine Gland Neoplasms
Disease
Ovarian Neoplasms
Neoplasms by Histologic Type
Immunoproliferative Disorders
Skin Diseases
Immune System Diseases
Hematologic Diseases
Myelodysplastic Syndromes

ClinicalTrials.gov processed this record on July 02, 2009