B-cell Chronic Lymphocytic LeukemiaPhase 1NCT00098488
17-N-Allylamino-17-Demethoxygeldanamycin With or Without Rituximab in Treating Patients With Relapsed B-Cell Chronic Lymphocytic Leukemia or Prolymphocytic Leukemia
A Phase 1 study testing tanespimycin and rituximab in people with B-cell Chronic Lymphocytic Leukemia and Prolymphocytic Leukemia, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This phase I trial is studying the side effects and best dose of 17-N-allylamino-17-demethoxygeldanamycin when given with or without rituximab in treating patients with relapsed B-cell chronic lymphocytic leukemia or prolymphocytic leukemia. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- B-cell Chronic Lymphocytic Leukemia, Prolymphocytic Leukemia, Refractory Chronic Lymphocytic Leukemia
- What is being tested?
- tanespimycin and rituximab
- 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
- Apr 2005to 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
- Histologically confirmed B-cell chronic lymphocytic leukemia or prolymphocytic leukemia requiring treatment, defined by 1 of the following criteria:
- Massive or progressive splenomegaly and/or lymphadenopathy
- Anemia (hemoglobin < 11 g/dL) OR thrombocytopenia (platelet count < 100,000/mm^3)
- Weight loss > 10% within the past 6 months
- Grade 2 or 3 fatigue
- Fevers > 100.5°F or night sweats for > 2 weeks with no evidence of infection
Show all 59Show fewer
- Progressive lymphocytosis with an increase of > 50% over a 2 month period OR an anticipated doubling time of < 6 months
- Relapsed disease
- Failed prior fludarabine or pentostatin therapy OR cannot receive fludarabine
- Lymphocyte count ≥ 5,000/mm^3
- Performance status - ECOG 0-2
- Performance status - Karnofsky 60-100%
- More than 12 weeks
- Bilirubin < 1.5 times upper limit of normal (ULN)
- AST and ALT ≤ 2.5 times ULN
- Creatinine ≤ 2.0 mg/dL
- LVEF > 40% by MUGA
- QTc < 450 msec for male patients and < 470 msec for female patients
- Resting ejection fraction ≥ 50% by MUGA or echocardiogram
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
- No significant cardiac disease including any of the following:
- New York Heart Association class III or IV heart failure
- History of myocardial infarction within the past year
- History of uncontrolled dysrhythmias
- Active ischemic heart disease within the past year
- Poorly controlled angina
- No history of serious ventricular arrhythmia (e.g., ventricular fibrillation, history of symptomatic or sustained ventricular tachycardia, nonsustained ventricular tachycardia > 3 beats within the past 6 months)
- No history of cardiac toxicity due to anthracyclines (e.g., doxorubicin hydrochloride, daunorubicin hydrochloride, or mitoxantrone hydrochloride)
- No other cardiac symptoms ≥ grade 2
- DLCO (i.e., oxygen diffusion capacity) ≥ 80% by pulmonary function testing
- Resting and exercise oxygen saturation ≥ 90% by pulse oximetry
- No pulmonary symptoms ≥ grade 2
- No history of pulmonary toxicity due to bleomycin or carmustine
- No significant, symptomatic pulmonary disease requiring oxygen or medications
- No ongoing pulmonary symptoms ≥ grade 2 including any of the following:
- Dyspnea on or off exertion
- Paroxysmal nocturnal dyspnea
- Significant pulmonary disease (e.g., chronic obstructive or restrictive pulmonary disease)
- No Medicare requirements for home oxygen (e.g., resting O_2 saturations ≥ 90% or desaturation to ≥ 90% with exertion)
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- HIV negative
- No history of allergic reaction attributed to compounds of similar chemical or biologic composition to 17-N-allylamino-17-demethoxygeldanamycin
- No history of serious allergic reaction to eggs
- No ongoing or active infection
- No psychiatric illness or social situation that would preclude study compliance
- No other uncontrolled illness that would preclude study participation
- More than 3 months since prior rituximab and recovered
- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
- More than 4 weeks since prior radiotherapy and recovered
- No prior radiotherapy that potentially included the heart in the field (e.g., mantle)
- No history of chest radiation
- No concurrent medications that prolong or may prolong QTc
- No concurrent antiarrhythmic drugs
- No other concurrent investigational agents
- No other concurrent anticancer therapy
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Ohio State University Medical Center
Columbus, Ohio, 43210
About this study
Official title: A Phase 1 Study of 17-allylamino-17-demethoxygeldanamycin (17-AAG) (NSC 330507; IND 57,966) and Rituximab in Patients With Relapsed B-cell Chronic Lymphocytic Leukemia (CLL)
This phase I trial is studying the side effects and best dose of 17-N-allylamino-17-demethoxygeldanamycin when given with or without rituximab in treating patients with relapsed B-cell chronic lymphocytic leukemia or prolymphocytic leukemia. Drugs used in chemotherapy, such as 17-N-allylamino-17-demethoxygeldanamycin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Monoclonal antibodies may kill cancer cells that are left after chemotherapy. Giving 17-N-allylamino-17-demethoxygeldanamycin with or without rituximab may kill more cancer cells.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated dose (MTD) of twice weekly 17-allylamino-17-demethoxygeldanamycin (17-AAG) in combination with weekly rituximab in patients with relapsed chronic lymphocytic leukemia (CLL).
II. To examine the pharmacology of twice weekly 17-AAG in combination with weekly rituximab in patients with relapsed CLL.
SECONDARY OBJECTIVES:
- To evaluate toxicity (using NCI CTCAE v3.0 criteria) and preliminary efficacy of twice weekly 17-AAG when used in combination with weekly rituximab in this patient population.
II. To examine the kinetics of depletion of PDK1/AKT-related proteins, mutant p53 and up-regulation of alternative targets that mediate resistance to therapy following treatment with twice weekly 17-AAG; and the relationship of this to spontaneous and drug-induced apoptosis in patients with relapsed CLL.
III. To examine the immunologic effects of twice weekly 17-AAG, in conjunction with weekly rituximab, in patients with relapsed CLL.
IV. To evaluate toxicity and preliminary efficacy of twice weekly 17-AAG as a single agent in this patient population.
OUTLINE: This is a multicenter, dose-escalation study of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG).
Patients receive 17-AAG intravenously (IV) over 2 hours on days 1, 4, 8, 11, 15 and 18 (course 1). Patients achieving ≥ 25% reduction in measurable disease after course 1 receive an additional course of single-agent 17-AAG approximately 10 days later in the absence of disease progression or unacceptable toxicity and provided absolute lymphocyte count continues to decrease. Patients failing to achieve a 25% reduction in measurable disease after course 1 OR with disease progression after courses 1 or 2 of single-agent 17-AAG proceed to combination therapy comprising 17-AAG IV over 2 hours on days 1, 4, 8, 11, 15, 18, and 22; and rituximab IV over 4 hours on days 1 and 2 and over 1 hour on days 4, 8, 15, and 22 in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of 17-AAG as a single agent or in combination with rituximab until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Patients are followed up at 2 months and then every 3 months for 2 years.
- Conditions
- B-cell Chronic Lymphocytic Leukemia, Prolymphocytic Leukemia, Refractory Chronic Lymphocytic Leukemia
- Being tested
- tanespimycin, rituximab
- 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.
tanespimycinDrug
Also called 17-AAG
Given IV
rituximabBiological
Also called IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (17-AGG and rituximab) | Experimental | Patients receive 17-AAG IV over 2 hours on days 1, 4, 8, 11, 15 and 18 (course 1). Patients achieving ≥ 25% reduction in measurable disease after course 1 receive an additional course of single-agent 17-AAG approximately 10 days later in the absence of disease progression or unacceptable toxicity and provided absolute lymphocyte count continues to decrease. Patients failing to achieve a 25% reduction in measurable disease after course 1 OR with disease progression after courses 1 or 2 of single-agent 17-AAG proceed to combination therapy comprising 17-AAG IV over 2 hours on days 1, 4, 8, 11, 15, 18, and 22; and rituximab IV over 4 hours on days 1 and 2 and over 1 hour on days 4, 8, 15, and 22 in the absence of disease progression or unacceptable toxicity. Receives: Drug: tanespimycin; Biological: rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD) of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG)
Defined at the dose level of 17-AAG at which 2 (or more) of 6 patients develop dose-limiting toxicity (DLT).
Measured: Week 4
Secondary outcomes (1)
Minimally effective pharmacological dose (MEPD) of 17-AAG based on down-modulation of the target protein Akt
Defined as the 17-AAG dose achieving >= 50% reduction in Akt protein expression.
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2004 (estimated)
- Study startApr 2005
- Primary completionApr 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for B-cell Chronic Lymphocytic LeukemiaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Thomas Lin, Principal investigator, Ohio State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00098488
- Sponsor's protocol ID
- NCI-2012-01460
- Other IDs
- OSU 0429, 2004C0058, NCI-6518, OSU-0429, CDR0000401516, R21CA115048
- Status last verified
- Jun 2013
- First submitted
- 7 Dec 2004
- Last updated
- 4 Jun 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study of 17-allylamino-17-demethoxygeldanamycin (17-AAG) (NSC 330507; IND 57,966) and Rituximab in Patients With Relapsed B-cell Chronic Lymphocytic Leukemia (CLL)
- ClinicalTrials.gov ID
- NCT00098488
- Acronym / sponsor ID
- NCI-2012-01460
- Conditions
- B-cell Chronic Lymphocytic Leukemia, Prolymphocytic Leukemia, Refractory Chronic Lymphocytic Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 30 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Apr 2005
- Primary completion
- Apr 2008 (actual)
- First posted
- 8 Dec 2004 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase I trial is studying the side effects and best dose of 17-N-allylamino-17-demethoxygeldanamycin when given with or without rituximab in treating patients with relapsed B-cell chronic lymphocytic leukemia or prolymphocytic leukemia. Drugs used in chemotherapy, such as 17-N-allylamino-17-demethoxygeldanamycin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Monoclonal antibodies may kill cancer cells that are left after chemotherapy. Giving 17-N-allylamino-17-demethoxygeldanamycin with or without rituximab may kill more cancer cells.
Detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated dose (MTD) of twice weekly 17-allylamino-17-demethoxygeldanamycin (17-AAG) in combination with weekly rituximab in patients with relapsed chronic lymphocytic leukemia (CLL).
II. To examine the pharmacology of twice weekly 17-AAG in combination with weekly rituximab in patients with relapsed CLL.
SECONDARY OBJECTIVES:
- To evaluate toxicity (using NCI CTCAE v3.0 criteria) and preliminary efficacy of twice weekly 17-AAG when used in combination with weekly rituximab in this patient population.
II. To examine the kinetics of depletion of PDK1/AKT-related proteins, mutant p53 and up-regulation of alternative targets that mediate resistance to therapy following treatment with twice weekly 17-AAG; and the relationship of this to spontaneous and drug-induced apoptosis in patients with relapsed CLL.
III. To examine the immunologic effects of twice weekly 17-AAG, in conjunction with weekly rituximab, in patients with relapsed CLL.
IV. To evaluate toxicity and preliminary efficacy of twice weekly 17-AAG as a single agent in this patient population.
OUTLINE: This is a multicenter, dose-escalation study of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG).
Patients receive 17-AAG intravenously (IV) over 2 hours on days 1, 4, 8, 11, 15 and 18 (course 1). Patients achieving ≥ 25% reduction in measurable disease after course 1 receive an additional course of single-agent 17-AAG approximately 10 days later in the absence of disease progression or unacceptable toxicity and provided absolute lymphocyte count continues to decrease. Patients failing to achieve a 25% reduction in measurable disease after course 1 OR with disease progression after courses 1 or 2 of single-agent 17-AAG proceed to combination therapy comprising 17-AAG IV over 2 hours on days 1, 4, 8, 11, 15, 18, and 22; and rituximab IV over 4 hours on days 1 and 2 and over 1 hour on days 4, 8, 15, and 22 in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of 17-AAG as a single agent or in combination with rituximab until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Patients are followed up at 2 months and then every 3 months for 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (17-AGG and rituximab) | Experimental | Drug: tanespimycin, Biological: rituximabPatients receive 17-AAG IV over 2 hours on days 1, 4, 8, 11, 15 and 18 (course 1). Patients achieving ≥ 25% reduction in measurable disease after course 1 receive an additional course of single-agent 17-AAG approximately 10 days later in the absence of disease progression or unacceptable toxicity and provided absolute lymphocyte count continues to decrease. Patients failing to achieve a 25% reduction in measurable disease after course 1 OR with disease progression after courses 1 or 2 of single-agent 17-AAG proceed to combination therapy comprising 17-AAG IV over 2 hours on days 1, 4, 8, 11, 15, 18, and 22; and rituximab IV over 4 hours on days 1 and 2 and over 1 hour on days 4, 8, 15, and 22 in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (59 listed)
- Histologically confirmed B-cell chronic lymphocytic leukemia or prolymphocytic leukemia requiring treatment, defined by 1 of the following criteria:
- Relapsed disease
- Failed prior fludarabine or pentostatin therapy OR cannot receive fludarabine
- Lymphocyte count ≥ 5,000/mm^3
- Performance status - ECOG 0-2
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| tanespimycinAlso: 17-AAGGiven IV | Drug | Treatment (17-AGG and rituximab) |
| rituximabAlso: IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8Given IV | Biological | Treatment (17-AGG and rituximab) |
Primary outcome
Maximum tolerated dose (MTD) of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG)
Time frame: Week 4
Defined at the dose level of 17-AAG at which 2 (or more) of 6 patients develop dose-limiting toxicity (DLT).
1 secondary outcome
Minimally effective pharmacological dose (MEPD) of 17-AAG based on down-modulation of the target protein Akt
Time frame: Day 1
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thomas Lin principal investigator
Ohio State University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing tanespimycin and rituximab 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 59 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: stopped early, as of the sponsor's last update on 4 Jun 2013. 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. 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 (MTD) of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) (time frame: Week 4). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Jun 2013.