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B-cell Chronic Lymphocytic LeukemiaPhase 1NCT01126502

Alvespimycin Hydrochloride in Treating Patients With Relapsed Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or B-Cell Prolymphocytic Leukemia

A Phase 1 study testing alvespimycin hydrochloride, diagnostic laboratory biomarker analysis and pharmacogenomic studies in people with B-cell Chronic Lymphocytic Leukemia and Prolymphocytic Leukemia, run by National Cancer Institute (NCI) at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This phase I trial is studying the side effects and the best dose of alvespimycin hydrochloride in treating patients with relapsed chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or B-cell prolymphocytic leukemia (B-PLL). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
alvespimycin hydrochloride, diagnostic laboratory biomarker analysis and pharmacogenomic studies
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteUnited States
Study dates
May 2010to Jun 2012
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

  • Patients must have histologically confirmed B-CLL/SLL or a B-PLL according to 2008 World Health Organization (WHO) diagnostic criteria
  • Patients must meet one or more of the following modified indications for treatment as described in the 2008 International Workshop on CLL (IWCLL) guidelines for the diagnosis and treatment of CLL:
  • Progressive disease, marked splenomegaly, and/or lymphadenopathy, or need to de-bulk disease for future allogeneic transplantation
  • Anemia (hemoglobin < 11 g/dL) or thrombocytopenia (platelet count < 100,000/mm^3)
  • Unexplained weight loss exceeding 10% of body weight over the past 6 months
  • Fatigue grade 2 or 3 as measured by Cancer Therapy Evaluation Program (CTEP) Active Version
Show all 29Show fewer
  • Fevers > 100.5º F OR night sweats for > 2 weeks without evidence of infection
  • Progressive lymphocytosis, with an increase exceeding 50% over a 2-month period or a doubling time of < 6 months
  • Patients must have received at least one prior therapy that includes either fludarabine or equivalent nucleoside analogue, or an alternative regimen if a contra-indication (i.e. autoimmune hemolytic anemia) or patient desire not to receive fludarabine exists
  • Children are excluded from this study but may be eligible for future pediatric trials
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Life expectancy of greater than 12 weeks
  • Total bilirubin =< 1.5 X institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional ULN
  • Creatinine within normal institutional limits
  • Creatinine clearance >= 50 mL/min/1.73 for patients with creatinine levels above institutional normal
  • QTc < 500 msec
  • Left ventricular ejection fraction (LVEF) > 40% by multi gated acquisition scan (MUGA)
  • No history of serious ventricular arrhythmia
  • No myocardial infarction or active ischemic heart disease within the past year
  • No New York Heart Association (NYHA) class III or IV congestive heart failure
  • No poorly controlled angina
  • No uncontrolled dysrhythmia requiring medication
  • No left bundle branch block
  • No history of congenital long QT syndrome
  • Pulse oximetry at rest or on exercise > 88%
  • No symptomatic pulmonary disease (Asthma or COPD that is controlled is acceptable)
  • Women of childbearing potential (WOCP) are required to have negative pregnancy test (serum) within 10-14 days and within 24 hours prior to the first dose of 17-DMAG; further, WOCP and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for a time frame of 14 days prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, the treating physician should be notified immediately
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier; corticosteroids alone will not be considered prior therapy, but must be discontinued at least 24 hours prior to the first day of 17-DMAG administration unless continued for indications other than the primary malignancy
  • Patients may not be receiving any other investigational agents
  • Patients with known central nervous system involvement should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to 17-DMAG
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection requiring iv antibiotics, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study because 17-DMAG is an agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with 17-DMAG, breastfeeding should be discontinued if the mother is treated with 17-DMAG
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with 17-DMAG

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Ohio State University Medical Center

    Columbus, Ohio, 43210

Other trials in United States

About this study

Official title: A Phase I Study of the Hsp90 Inhibitor 17-DMAG (Alvespimycin) in Patients With Relapsed Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL), and B-cell Prolymphocytic Leukemia (B-PLL)

This phase I trial is studying the side effects and the best dose of alvespimycin hydrochloride in treating patients with relapsed chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or B-cell prolymphocytic leukemia (B-PLL). Drugs used in chemotherapy, such as alvespimycin hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximum tolerated dose (MTD) of 17-DMAG in patients with relapsed CLL/SLL and B-PLL.

II. To define the dose limiting toxicity (DLT) of 17-DMAG in patients with relapsed CLL/SLL and B-PLL.

SECONDARY OBJECTIVES:

  1. To assess preliminary efficacy of 17-DMAG in patients with relapsed CLL/SLL and B-PLL.

II. To determine the pharmacokinetics of 17-DMAG in patients with relapsed CLL/SLL and B-PLL.

III. To determine the feasibility of measuring pharmacodynamic markers of 17-DMAG including the Hsp90 client proteins Akt and IKK-alpha/IKK-beta.

IV. To determine if FoxD3 and downstream genes such as EPHA7 and ID4 are re-expressed in CLL cells following treatment with 17-DMAG.

  1. To correlate pharmacokinetic features of 17-DMAG with response, toxicity and pharmacodynamic endpoints.

VI. To correlate risk parameters such as ZAP-70 with response to 17-DMAG.

OUTLINE: This is a dose-escalation study.

Patients receive alvespimycin hydrochloride intravenously (IV) over 60 minutes on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed every 3 months for 2 years.

Being tested
alvespimycin hydrochloride, diagnostic laboratory biomarker analysis, pharmacogenomic studies, pharmacological study
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Prolymphocytic

What participants receive

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

  • alvespimycin hydrochlorideDrug

    Also called 17-DMAG HCL, KOS-1022

    Given IV

  • diagnostic laboratory biomarker analysisOther

  • pharmacogenomic studiesOther

    Also called Pharmacogenomic Study

  • pharmacological studyOther

    Also called pharmacological studies

Study groups in NCT01126502
Study groupRoleWhat they receive
Treatment (enzyme inhibitor therapy)ExperimentalPatients receive alvespimycin hydrochloride IV over 60 minutes on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Receives: Drug: alvespimycin hydrochloride; Other: diagnostic laboratory biomarker analysis; Other: pharmacogenomic studies; Other: pharmacological study

What is being measured

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

  1. Maximum tolerated dose of 17-DMAG

    Defined as the maximum dose level where at most 1 of 6 patients experience dose-limiting toxicity.

    Measured: 21 days

Timeline

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

  1. First posted19 May 2010 (estimated)
  2. Study startMay 2010
  3. Primary completionJun 2012
  4. Study completionJun 2012

Why it stopped: Administratively Complete.

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
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01126502
Sponsor's protocol ID
NCI-2011-01374
Other IDs
NCI-2011-01374, OSU-10021, CDR0000738867, OSU 10021, 8302, P30CA016058, U01CA076576
Status last verified
Jan 2014
First submitted
18 May 2010
Last updated
4 Nov 2015
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing alvespimycin hydrochloride, diagnostic laboratory biomarker analysis and pharmacogenomic studies in people with B-cell Chronic Lymphocytic Leukemia and Prolymphocytic Leukemia, run by National Cancer Institute (NCI) at 1 site 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 29 inclusion and 7 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: stopped early, as of the sponsor's last update on 4 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 was stopped early (reason given: Administratively Complete.). Results are not available in the source record.

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?

Maximum tolerated dose of 17-DMAG (time frame: 21 days). 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 NCT01126502.

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 4 Nov 2015.

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