AzTrials
AzTrials

Chronic Lymphocytic LeukemiaPhase 1/2NCT00676871

A Study to Evaluate the Safety, Tolerability, and Antitumor Activity of Continuous Intravenous Infusion of MEDI-538 in Adults With B-Cell Chronic Lymphocytic Leukemia (CLL)

A Phase 1/2 study testing MEDI-538 in people with Chronic Lymphocytic Leukemia, run by MedImmune LLC.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial summary

Phase 1: Evaluate the safety and tolerability of MEDI-538 given by escalated doses with continuous IV infusion for 4 weeks in adult patients with CLL. Determine the maximum tolerated dose (MTD) of MEDI-538 administered by continuous IV infusion for 4 weeks in this patient population Describe the pharmacokinetics (PK)… Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Chronic Lymphocytic Leukemia
What is being tested?
MEDI-538
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
No sites listed yet
Study dates
Jun 2008to Jun 2011
Phase
Phase 1/2
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 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Adult men or women at least 18 years of age;
  • Written informed consent and Heath Insurance Portability and Accountability Act (HIPAA) authorization (applies to covered entities in the USA only) obtained from the patient prior to performing any study-related procedures, including screening visits;
  • Previous confirmation of B-cell CLL with a characteristic immunophenotype by flow cytometry;
  • MRD positivity, determined by 4-color flow cytometry of bone marrow or peripheral blood in all patients following previous therapy for CLL;
  • Measurable and/or residual disease following previous therapy for CLL as follows:
  • Measurable disease, as determined by NCI-WG criteria, following standard first-line or salvage therapy; this includes patients with PD, SD, or PR (Phase 1 only);
Show all 17Show fewer
  • Residual disease as determined by measurable disease (ie, PD, SD, or PR) or by MRD positivity, determined by 4-color flow cytometry of bone marrow and/or peripheral blood in patients with CR or nPR (Phase 2 only);
  • Time from completing last therapy for CLL is ≥ 3 months but ≤ 1 year;
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2;
  • Presence of live-in companion (relative or friend) who agrees to NOT leave the patient unattended for > 8 hours per day;
  • Patient agrees to refrain from engaging in hazardous occupations or activities requiring complete mental alertness such as operating machinery or driving a motor vehicle;
  • Females, unless surgically sterile or at least 1 year post-menopausal, must use an effective method of avoiding pregnancy (including oral, transdermal, or implanted contraceptives, intrauterine device, female condom with spermicide, diaphragm with spermicide, cervical cap, abstinence, use of a condom with spermicide by the sexual partner or sterile sexual partner) for 21 days prior to the first dose of MEDI-538, and must agree to continue using such precautions through 3 months after the last dose of MEDI-538. Cessation of birth control after this point should be discussed with a responsible physician. Males, unless surgically sterile, must likewise use an effective method of birth control (condom with spermicide) and must agree to continue using such precautions through 3 months after the last dose of MEDI-538;
  • Hemoglobin ≥ 10.0 g/dL and platelets > 75.0 x 109/L;
  • Total bilirubin ≤ 1.5 x ULN; aspartate transaminase (AST), alanine transaminase (ALT), amylase and lipase ≤ 2 x ULN;
  • Serum creatinine ≤ 2 x ULN and creatinine clearance ≥ 50 mL/min;
  • Absolute neutrophil count (ANC) > 1.0 × 109/L; and
  • For patients who have received previous treatment with alemtuzumab, CD4 counts must be > 200 cells/μL with a negative status for cytomegalovirus (CMV) antigen.

Who cannot join

  • Receipt of MEDI-538 in any previous clinical study;
  • History of allergy or reaction to any component of the MEDI-538 formulation;
  • History of malignancy other than CLL within 5 years prior to study entry, with the exception of basal cell carcinoma of the skin or carcinoma in situ of the cervix successfully treated with curative therapy;
  • Fludarabine-refractory CLL, defined as failure to achieve a PR or CR/nPR to at least one fludarabine-containing regimen, disease progression while on fludarabine treatment, or disease progression in responders within 6 months of last dose of fludarabine;
  • Known or suspected CNS involvement;
  • Clinical history of significant CNS pathology, eg, uncontrolled headaches, multiple occurrences of confusion, dementia, multiple previous infarcts, or major brain surgery;
Show all 22Show fewer
  • Active infection or known bacteremia. Patients with documented evidence of culture positive sepsis or active infection requiring IV antibiotic therapy must complete a full course of antibiotic treatment with no clinical or laboratory evidence of bacterial infection at least 2 weeks prior to starting therapy with MEDI-538.
  • Vaccination (either preventive or therapeutic for infectious disease or cancer) within 2 weeks prior to initiation of MEDI-538;
  • Infection with human immunodeficiency virus (HIV-1 or HIV-2), chronic infection with hepatitis B or C, or acute infection with hepatitis A;
  • History of serious, chronic autoimmune disease, eg, rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis;
  • Elective surgery planned during the study period through 30 days after discontinuation of MEDI-538;
  • Autologous stem cell transplantation within 26 weeks prior to study entry;
  • Allogenic stem cell transplantation or any other solid organ transplant;
  • Regular dose of systemic corticosteroids during the 4 weeks prior to initiation of MEDI-538 or anticipated need of corticosteroids exceeding prednisone 20 mg/day or equivalent during the trial, or any other systemic immunosuppressive therapy within 4 weeks prior to study entry;
  • Any contraindication to chronic anticoagulation with low-molecular weight heparin (LMWH);
  • Inability for safe placement and prolonged use (at least 4 weeks) of a central venous catheter;
  • Contraindication to any of the protocol-specified concomitant medications (methylprednisolone, antacids, or antihistamines) during this study;
  • Presence of known human anti-murine antibodies or hypersensitivity to immunoglobulins;
  • Pregnancy (females of childbearing potential must have a negative urine pregnancy test on the day of the first dose of MEDI-538, prior to dosing) or nursing;
  • Evidence of any uncontrolled systemic disease (other than CLL), including autoimmune hemolytic anemia;
  • Any finding upon physical examination or history of any disease or behavior that, in the opinion of the investigator or medical monitor, may compromise the safety of the patient in the study or confound the analysis of the study; or
  • Inability to meet social environment requirements for outpatient therapy (see Section 3.3.4.2).

About this study

Official title: A Phase 1/2, Open-Label, Single-Arm, Dose-Escalation Study to Evaluate the Safety, Tolerability, and Antitumor Activity of Continuous Intravenous Infusion of the Bispecific T-Cell Engager MEDI-538 In Adults With B-Cell Chronic Lymphocytic Leukemia(CLL)Who Have Residual Disease Following Previous Therapy for CLL

Phase 1:

  • Evaluate the safety and tolerability of MEDI-538 given by escalated doses with continuous IV infusion for 4 weeks in adult patients with CLL.
  • Determine the maximum tolerated dose (MTD) of MEDI-538 administered by continuous IV infusion for 4 weeks in this patient population
  • Describe the pharmacokinetics (PK) of MEDI-538
  • Describe the immunogenicity (IM) of MEDI-538
  • Determine the overall response, which is defined as follows: (1) conversion from PD/SD to PR/nPR/CR or conversion from PR to nPR/CR using standard NCI-WG criteria; or (2) conversion from MRD positivity to MRD negativity using 4-color flow cytometry; and
  • Describe any antitumor activity (ie, time to response and duration of response) of MEDI-538 in this patient population.
Read more

Phase 2:

  • To determine the overall response in adult patients with CLL who have residual disease following previous therapy for CLL.
  • Describe the safety,PK,and IM of MEDI-538
  • Determine the time to MRD relapse
  • Determine the antitumor activity (ie, time to response, duration of response,and time to progression [TTP])of MEDI-538 in this patient population.
Read the detailed description

Phase 1:

  • Evaluate the safety and tolerability of MEDI-538 at doses of 5, 10, 15, 30, 45, or 60 mg/m2/24h by continuous IV infusion for 4 weeks in adult patients with CLL who have measurable disease following previous therapy for CLL. Patients with measurable disease include patients who demonstrated PD, SD, or PR following previous therapy for CLL; and
  • Determine the maximum tolerated dose (MTD) of MEDI-538 administered by continuous IV infusion for 4 weeks in this patient population;
  • Describe the pharmacokinetics (PK) of MEDI-538
  • Describe the immunogenicity (IM) of MEDI-538
  • Determine the overall response, which is defined as follows: (1) conversion from PD/SD to PR/nPR/CR or conversion from PR to nPR/CR using standard NCI-WG criteria; or (2) conversion from MRD positivity to MRD negativity using 4-color flow cytometry; and
  • Describe any antitumor activity (ie, time to response and duration of response) of MEDI-538 in this patient population.

Phase 2:

  • Determine the overall response in adult patients with CLL who have residual disease following previous therapy for CLL.
  • Describe the safety of MEDI-538
  • Describe the PK of MEDI-538
  • Describe the IM of MEDI-538
  • Determine the time to MRD relapse
  • Determine the antitumor activity (ie, time to response, duration of response, and time to progression [TTP]) of MEDI-538 in this patient population.
Being tested
MEDI-538
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

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

  • MEDI-538Drug

    Dose one of MEDI 538 as a continuous IV infusion - dose level is 5 mg/m2/24h (Phase 1)

  • MEDI-538Drug

    Dose two of MEDI 538 as a continuous IV infusion - dose level is 10 mg/m2/24h (Phase 1)

  • MEDI-538Drug

    Dose three of MEDI 538 as a continuous IV infusion-dose level is 15mg/m2/24h (Phase 1)

  • MEDI-538Drug

    Dose four of MEDI 538 as a continuous IV infusion - dose level is 30 mg/m2/24h(Phase 1)

  • MEDI-538Drug

    Dose five of MEDI 538 as a continuous IV infusion - dose level is 45 mg/m2/24h (Phase 1)

  • MEDI-538Drug

    Dose six of MEDI 538 as a continuous IV infusion - dose level is 60 mg/m2/24h (Phase 1)

  • MEDI-538Drug

    Phase 2 part of the study, 20 to 60 patients will be treated with MEDI 538 as a continuous IV infusion through a central line catheter. The dose of MEDI-538 will be determined in the Phase 1 part of the study.

Study groups in NCT00676871
Study groupRoleWhat they receive
1ExperimentalMEDI-538
Receives: Drug: MEDI-538
2ExperimentalMEDI-538
Receives: Drug: MEDI-538
3ExperimentalMEDI-538
Receives: Drug: MEDI-538
4ExperimentalMEDI-538
Receives: Drug: MEDI-538
5ExperimentalMEDI-538
Receives: Drug: MEDI-538
6ExperimentalMEDI-538
Receives: Drug: MEDI-538
7ExperimentalMEDI-538
Receives: Drug: MEDI-538

What is being measured

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

  1. The primary outcome of the Phase 1 part of the study are to evaluate the safety, tolerability, and MTD of MEDI-538 by continuous IV infusion for 4 weeks in adult patients with CLL who have measurable disease following previous therapy for CLL.

    Measured: 30 days after patient's final dose of study drug

  2. The primary objective of the Phase 2 part of the study is to determine the overall response in adult patients with CLL who have residual disease following previous therapy for CLL.

    Measured: 30 days after patient's final dose of study drug

Secondary outcomes (2)

  1. The secondary outcome of the Phase 1 part of the study include measurement of the PK, IM, and antitumor activity of MEDI-538 in this patient population.

    Measured: 30 days after patient's final dose of study drug

  2. The secondary objectives of the Phase 2 part of the study include safety, measurement of the PK, IM, and antitumor activity of MEDI-538 in this patient population.

    Measured: 30 days after patient's final dose of study drug

Timeline

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

  1. First posted13 May 2008 (estimated)
  2. Study startJun 2008
  3. Primary completionMar 2010 (estimated)
  4. Study completionJun 2011 (estimated)

Why it stopped: Replacing this trial with a new trial.

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00676871
Sponsor's protocol ID
MI-CP155
Status last verified
Sep 2008
First submitted
8 May 2008
Last updated
5 Sep 2008
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing MEDI-538 in people with Chronic Lymphocytic Leukemia, run by MedImmune LLC.

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 17 inclusion and 22 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: withdrawn, as of the sponsor's last update on 5 Sep 2008. Status can change between updates, so confirm with the study contact before making plans.

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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 was withdrawn before enrolling participants, so there are no results.

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?

The primary outcome of the Phase 1 part of the study are to evaluate the safety, tolerability, and MTD of MEDI-538 by continuous IV infusion for 4 weeks in adult patients with CLL who have measurable disease following previous therapy for CLL. (time frame: 30 days after patient's final dose of study drug). The study lists 2 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 NCT00676871.

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 5 Sep 2008; AzTrials last refreshed its copy on 31 Oct 2026.

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