Ipilimumab After Allogeneic Stem Cell Transplant in Treating Patients With Persistent or Progressive Cancer

March 26, 2013 updated by: National Cancer Institute (NCI)

CTLA-4 Blockade With MDX-010 to Induce Graft-Versus-Malignancy Effects Following Allogeneic Hematopoietic Stem Cell Transplantation

This phase I trial is studying how well ipilimumab works after allogeneic stem cell transplant in treating patients with persistent or progressive cancer. Monoclonal antibodies can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the dose of MDX-010 (ipilimumab) that can safely be administered to patients with persistent or progressive malignancy following allo-HCT.

II. To determine the pharmacokinetics of different doses of MDX-010 administered as a single dose to patients with persistent or progressive malignancy following allo-HCT.

III. By assessment of aims 1 and 2, to determine the best dosing regimen for further study of CTLA-4 blockade in conjunction with escalating dose donor-leukocyte infusions (DLI) in patients with evidence of residual or progressive malignancy following allo-HCT.

IV. To assess if there is preliminary evidence of efficacy following the administration of MDX-010 in this population.

OUTLINE:

Patients receive ipilimumab intravenously (IV) over 90 minutes.

Cohorts of 3-6 patients receive escalating doses of ipilimumab 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 ipilimumab 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.

Study Type

Interventional

Enrollment (Actual)

21

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • La Jolla, California, United States, 92037
        • Scripps Clinic - La Jolla
      • La Jolla, California, United States, 92093-0960
        • University of California San Diego
    • Georgia
      • Atlanta, Georgia, United States, 30342
        • Blood and Marrow Transplant Group of Georgia
      • Atlanta, Georgia, United States, 30342
        • Northside Hospital
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana-Farber Harvard Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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
  • 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
  • Cytogenetic progression as 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 (0% Ph1-positive cells) to partial response (1-34% Ph1-positive cells); PR to minor response (35-94% Ph1-positive cells); or MR to no response (95-100% Ph1-positive cells)
  • 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
  • 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

  • OR; Hematologic persistence evidenced by cytopenias not attributable to other post-transplant causes accompanied by characteristic morphological changes more than 90 days after AHSCT, or 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/mm3, greater than 25% increase in measurable lymphadenopathy, persistence of absolute lymphocytosis of > 5,000/mm3 at day 90 or later after AHSCT, persistence of lymphadenopathy of ≥ 3 cm in diameter at day 90 or later after AHSCT

  • Aggressive 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 OR;
  • 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 OR
  • 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
  • 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
  • ECOG 0-2
  • Life expectancy: More than 3 months
  • 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
  • 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
  • No prior anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010)
  • 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
  • OR Cytogenetic persistence evidenced by any Ph1-positive metaphases in bone marrow after day 90 post-AHSCT

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (ipilmumab and donor lymphocyte infusion)
Patients receive ipilimumab IV over 90 minutes. Cohorts of 3-6 patients receive escalating doses of ipilimumab until the 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 ipilimumab administration and no evidence of graft-versus-host disease receive donor lymphocyte infusions every 60 days for a total of 3 infusions.
Drug: ipilimumab
Given IV
Other Names:
  • MDX-010
  • anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody
  • MDX-CTLA-4
  • monoclonal antibody CTLA-4
Drug: therapeutic allogeneic lymphocytes
Given IV
Other Names:
  • ALLOLYMPH

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence of grade 3 and 4 acute GVHD based on NCI CTC
Time Frame: 60 days following administration of ipilimumab
60 days following administration of ipilimumab
Incidence of graft rejection following ipilimumab defined as the percentage of patients entered who demonstrate =< 10% donor T-cell chimerism
Time Frame: Post-infusion day 60
Post-infusion day 60
Autoimmune reaction defined as >= grade 3 dysfunction of a vital organ or the graft
Time Frame: Up to 5 years
Up to 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Polyclonal T-cell activation monitored by clinical assessment and laboratory evidence (anti CD3, CD4, CD8) and markers of activation (anti CD69, CD25, CD44 and MHC class II)
Time Frame: Up to 5 years
Up to 5 years
Incidence of extensive stage chronic GVHD
Time Frame: Post-infusion day 360
Post-infusion day 360
Disease response
Time Frame: Up to day 360 post ipilimumab infusion
Up to day 360 post ipilimumab infusion
Disease-free survival
Time Frame: Up to day 360 following antibody infusion
Kaplan- Meier estimates of probability will be used.
Up to day 360 following antibody infusion
Overall survival
Time Frame: Up to 360 days post-infusion
Kaplan- Meier estimates of probability will be used.
Up to 360 days post-infusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Ewa Carrier, University of California, San Diego

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2003

Primary Completion (Actual)

April 1, 2008

Study Registration Dates

First Submitted

May 6, 2003

First Submitted That Met QC Criteria

May 6, 2003

First Posted (Estimate)

May 7, 2003

Study Record Updates

Last Update Posted (Estimate)

March 27, 2013

Last Update Submitted That Met QC Criteria

March 26, 2013

Last Verified

March 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2009-00042
  • 040749
  • P-6082
  • NCI-6082
  • CDR0000301644
  • R01CA093891 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Stage I Multiple Myeloma

Clinical Trials on ipilimumab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Switzerland

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe