AzTrials
AzTrials

Adult Acute Myeloid Leukemia With 11q23 (MLL) AbnormalitiesPhase 1NCT00060372

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

A Phase 1 study testing ipilimumab and therapeutic allogeneic lymphocytes in people with Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities and Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), run by National Cancer Institute (NCI) at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
ipilimumab and therapeutic allogeneic lymphocytes
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
5 sitesUnited States
Study dates
Apr 2003to Apr 2008
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
Show all 38Show fewer
  • 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

Who cannot join

None listed.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • Blood and Marrow Transplant Group of Georgia

    Atlanta, Georgia, 30342

  • Northside Hospital

    Atlanta, Georgia, 30342

  • Dana-Farber Harvard Cancer Center

    Boston, Massachusetts, 02115

  • Scripps Clinic - La Jolla

    La Jolla, California, 92037

  • University of California San Diego

    La Jolla, California, 92093-0960

Other trials in United States

About this study

Official title: 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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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.

Being tested
ipilimumab, therapeutic allogeneic lymphocytes
Medical subject headings
Congenital Abnormalities, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Neoplasms, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Burkitt Lymphoma, Lymphoma, Large B-Cell, Diffuse

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ipilimumabDrug

    Also called anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody, MDX-010, MDX-CTLA-4, monoclonal antibody CTLA-4

    Given IV

  • therapeutic allogeneic lymphocytesDrug

    Also called ALLOLYMPH

    Given IV

Study groups in NCT00060372
Study groupRoleWhat they receive
Treatment (ipilmumab and donor lymphocyte infusion)ExperimentalPatients 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.
Receives: Drug: ipilimumab; Drug: therapeutic allogeneic lymphocytes

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of grade 3 and 4 acute GVHD based on NCI CTC

    Measured: 60 days following administration of ipilimumab

  2. Incidence of graft rejection following ipilimumab defined as the percentage of patients entered who demonstrate =< 10% donor T-cell chimerism

    Measured: Post-infusion day 60

  3. Autoimmune reaction defined as >= grade 3 dysfunction of a vital organ or the graft

    Measured: Up to 5 years

Secondary outcomes (5)

  1. 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)

    Measured: Up to 5 years

  2. Incidence of extensive stage chronic GVHD

    Measured: Post-infusion day 360

  3. Disease response

    Measured: Up to day 360 post ipilimumab infusion

  4. Disease-free survival

    Kaplan- Meier estimates of probability will be used.

    Measured: Up to day 360 following antibody infusion

  5. Overall survival

    Kaplan- Meier estimates of probability will be used.

    Measured: Up to 360 days post-infusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 May 2003 (estimated)
  2. Study startApr 2003
  3. Primary completionApr 2008

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00060372
Sponsor's protocol ID
NCI-2009-00042
Other IDs
040749, P-6082, NCI-6082, CDR0000301644, R01CA093891
Status last verified
Mar 2013
First submitted
6 May 2003
Last updated
27 Mar 2013
Results posted
No

Publications

  • Bashey A, Medina B, Corringham S, Pasek M, Carrier E, Vrooman L, Lowy I, Solomon SR, Morris LE, Holland HK, Mason JR, Alyea EP, Soiffer RJ, Ball ED. CTLA4 blockade with ipilimumab to treat relapse of malignancy after allogeneic hematopoietic cell transplantation. Blood. 2009 Feb 12;113(7):1581-8. doi: 10.1182/blood-2008-07-168468. Epub 2008 Oct 30.

    PubMed 18974373

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ipilimumab and therapeutic allogeneic lymphocytes in people with Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities and Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), run by National Cancer Institute (NCI) at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 38 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Mar 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of grade 3 and 4 acute GVHD based on NCI CTC (time frame: 60 days following administration of ipilimumab). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00060372, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2013.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in