Adult Acute Basophilic LeukemiaPhase 1NCT00103272
17-N-Allylamino-17-Demethoxygeldanamycin and Bortezomib in Treating Patients With Relapsed or Refractory Hematologic Cancer
A Phase 1 study testing tanespimycin and bortezomib in people with Adult Acute Basophilic Leukemia and Adult Acute Eosinophilic 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 and bortezomib in treating patients with relapsed or refractory hematologic cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adult Acute Basophilic Leukemia, Adult Acute Eosinophilic Leukemia, Adult Acute Megakaryoblastic Leukemia (M7)
- What is being tested?
- tanespimycin and bortezomib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 74 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 or cytologically confirmed diagnosis of 1 of the following hematologic malignancies:
- Acute myeloid leukemia or acute lymphoblastic leukemia
- Not a candidate for potentially curative therapy
- WBC ≤ 10,000/mm^3 OR WBC ≤ 40,000/mm^3 that is stable for 5 days (hydroxyurea allowed)
- No acute promyelocytic leukemia
- Non-Hodgkin's lymphoma (NHL), including 1 of the following subtypes:
Show all 78Show fewer
- Small lymphocytic lymphoma
- Marginal zone lymphoma
- Lymphoplasmacytic lymphoma
- Follicular lymphoma
- Mantle cell lymphoma
- Diffuse large B-cell lymphoma
- Anaplastic large cell lymphoma
- Peripheral T-cell lymphoma
- Extranodal NK/T cell lymphoma (nasal and nasal type)
- Enteropathy-type T-cell lymphoma
- Hepatosplenic T-cell lymphoma
- Angioimmunoblastic T-cell lymphoma
- Subcutaneous panniculitis-like T-cell lymphoma
- Chronic lymphocytic leukemia (CLL)
- Patients with NHL or CLL must meet the following criteria:
- Ineligible for, or refused potentially curative stem cell transplantation
- Transformed lymphoma/Richter's transformation, defined as the transformation of low-grade lymphoma, including follicular lymphoma, CLL, or small lymphocytic lymphoma to high-grade lymphoma (i.e., diffuse large cell lymphoma) allowed at time of transformation
- Evidence of ≥ 50% bone marrow involvement at the time of enrollment OR tumor tissue accessible for biopsy (for patients enrolled after the maximum tolerated dose [MTD] is determined)
- Absolute neutrophil count ≥ 1,000/mm^3
- Platelet count ≥ 100,000/mm^3
- Relapsed or refractory disease
- Willing to undergo serial bone marrow biopsy (for patients enrolled after the MTD is determined)
- No untreated or active CNS leukemia or lymphoma
- Performance status - ECOG 0-2
- At least 12 weeks
- Bilirubin ≤ 1.5 mg/dL
- AST and ALT ≤ 2.5 times upper limit of normal
- Creatinine ≤ 2.0 mg/dL
- No uncontrolled cardiac disease
- No New York Heart Association class III-IV symptomatic congestive heart failure
- No unstable angina pectoris
- No serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation > 3 beats in a row) within the past 6 months
- No other uncontrolled cardiac arrhythmia or requiring antiarrhythmic drugs
- No myocardial infarction within the past year
- No active ischemic heart disease within the past year
- No congenital long QT syndrome
- No left bundle branch block
- QTc ≥ 450 msec (for men) or 470 (for women) on ECG/EKG
- No history of LVEF < 50% by MUGA or echocardiogram
- Resting ejection fraction ≥ 50% by MUGA or echocardiogram
- No prior history of cardiac toxicity after receiving anthracycline therapy (e.g., doxorubicin hydrochloride, daunorubicin hydrochloride, or mitoxantrone hydrochloride)
- No uncontrolled pulmonary disease
- No symptomatic pulmonary disease requiring oxygen or medications
- DLCO (i.e., oxygen diffusion capacity) ≥ 80% on pulmonary function testing
- Resting and exercise oxygen saturation ≥ 90% by pulse oximetry
- No ongoing pulmonary symptoms ≥ grade 2 including any of the following:
- Dyspnea on or off exertion
- Paroxysmal nocturnal dyspnea
- Significant pulmonary disease including chronic obstructive or restrictive pulmonary disease
- No prior history of pulmonary toxicity after bleomycin or carmustine
- No Medicare requirement for home oxygen (e.g., Resting O_2 saturation ≥ 90% or desaturation to ≥ 90% with exertion)
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- HIV negative
- No preexisting sensory or motor peripheral neuropathy ≥ grade 2
- No history of allergic reaction to eggs
- No ongoing or active infection
- No psychiatric illness or social situation that would preclude study compliance
- No other uncontrolled illness
- Prior stem cell transplantation for relapsed or refractory disease allowed
- At least 2 weeks since prior immunotherapy and recovered
- At least 2 weeks since prior chemotherapy (excluding hydroxyurea) and recovered
- No other concurrent chemotherapy
- No concurrent routine corticosteroids except for treatment of other medical problems (e.g., pulmonary, rheumatologic, or adrenal disorders)
- At least 2 weeks since prior radiotherapy and recovered
- No prior radiotherapy that potentially included the heart in the field (e.g., mantle)
- No prior history of chest radiation
- No concurrent palliative radiotherapy
- At least 2 weeks since prior investigational therapy
- Prior bortezomib allowed
- No other concurrent commercial or investigational agents or therapies for the malignancy
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 I Study of PS-341 (Velcade, Bortezomib) in Combination With 17-allylamino-17-demethoxygeldanamycin (17-AAG) in Patients With Relapsed or Refractory Hematologic Malignancies
This phase I trial is studying the side effects and best dose of 17-N-allylamino-17-demethoxygeldanamycin and bortezomib in treating patients with relapsed or refractory hematologic cancer. 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. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving 17-N-allylamino-17-demethoxygeldanamycin together with bortezomib may kill more cancer cells.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated dose (MTD) of PS-341 (Velcade, Bortezomib) in combination with 17-allyamino-17-demethoxygeldanamycin (17-AAG) in patients with relapsed or refractory acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL).
II. To determine the MTD of PS-341 in combination with 17-AAG in patients with relapsed or refractory chronic lymphocytic leukemia (CLL), and non-Hodgkin's lymphoma (NHL).
III. To define the specific toxicities and the dose limiting toxicity (DLT) of PS-341 in combination with 17-AAG in the treatment of patients with relapsed or refractory hematologic malignancies.
SECONDARY OBJECTIVES:
- To determine the pharmacokinetics of 17-AAG alone and in combination with PS-341 in patients with AML, ALL, CLL, and NHL.
II. To evaluate 20S proteasome inhibition following combination therapy with 17-AAG and PS-341 in patients with AML, ALL, CLL, and NHL.
III. To assess the relationship between FLT3 mutational status and leukemic cell response to PS-341 and 17-AAG in patients with AML.
IV. To assess the relationship between Bcl-2 over-expression and response to 17-AAG and PS-341 in patients with AML and NHL.
- To evaluate the effects of the combination of PS-341 and 17-AAG on Hsp90 and NF-kappaB and their downstream targets including Hsp70, Akt, phosphorylated Akt, p21, and caspases 3 and 9 in patient-derived primary AML and NHL cells.
OUTLINE: This is a dose-escalation study. Patients are stratified according to diagnosis (acute myeloid leukemia [AML] or acute lymphoblastic leukemia vs chronic lymphoctyic leukemia or non-Hodgkin's lymphoma [NHL]).
Patients receive 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) intravenously (IV) over 1-6 hours on days 1, 4, 8, and 11 and bortezomib IV over 3-5 seconds on days 4, 8, and 11 of course 1 and on days 1, 4, 8, and 11 of all subsequent courses.
Treatment repeats every 21 days for 3-12 courses provided patient is receiving clinical benefit. Patients achieving objective response may discontinue therapy to undergo stem cell transplantation.Cohorts of 3-6 patients with receive escalating doses of 17-AAG and bortezomib 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.
After the MTD is determined, an additional 20 patients (10 per stratum with AML or follicular NHL) are enrolled and receive 17-AAG and bortezomib as above at the MTD.
- Conditions
- Adult Acute Basophilic Leukemia, Adult Acute Eosinophilic Leukemia, Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monoblastic Leukemia (M5a), Adult Acute Monocytic Leukemia (M5b)
- Being tested
- tanespimycin, bortezomib
- Medical subject headings
- Leukemia, Basophilic, Acute, Leukemia, Eosinophilic, Acute, Leukemia, Megakaryoblastic, Acute, Leukemia, Monocytic, Acute, Leukemia, Myeloid, Acute, Congenital Abnormalities, Leukemia, Myelomonocytic, Acute, Leukemia, Erythroblastic, Acute
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
bortezomibDrug
Also called LDP 341, MLN341, VELCADE
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (17-AAG and bortezomib) | Experimental | Patients receive 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) IV over 1-6 hours on days 1, 4, 8, and 11 and bortezomib IV over 3-5 seconds on days 4, 8, and 11 of course 1 and on days 1, 4, 8, and 11 of all subsequent courses.
Treatment repeats every 21 days for 3-12 courses provided patient is receiving clinical benefit. Patients achieving objective response may discontinue therapy to undergo stem cell transplantation. Receives: Drug: tanespimycin; Drug: bortezomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD) of bortezomib) in combination with 17-AAG)
Defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Measured: Day 21
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2005 (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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Adult Acute Basophilic 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
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Kristie Blum, Principal investigator, Ohio State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00103272
- Sponsor's protocol ID
- NCI-2012-01463
- Other IDs
- OSU 0448, NCI-6520, CDR0000409584, OSU-2004C0084, OSU-0448, U01CA076576
- Status last verified
- Jun 2013
- First submitted
- 7 Feb 2005
- Last updated
- 4 Jun 2013
- Results posted
- No
Publications
Walker AR, Klisovic R, Johnston JS, Jiang Y, Geyer S, Kefauver C, Binkley P, Byrd JC, Grever MR, Garzon R, Phelps MA, Marcucci G, Blum KA, Blum W. Pharmacokinetics and dose escalation of the heat shock protein inhibitor 17-allyamino-17-demethoxygeldanamycin in combination with bortezomib in relapsed or refractory acute myeloid leukemia. Leuk Lymphoma. 2013 Sep;54(9):1996-2002. doi: 10.3109/10428194.2012.760733. Epub 2013 Jan 24.
PubMed 23256542
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 I Study of PS-341 (Velcade, Bortezomib) in Combination With 17-allylamino-17-demethoxygeldanamycin (17-AAG) in Patients With Relapsed or Refractory Hematologic Malignancies
- ClinicalTrials.gov ID
- NCT00103272
- Acronym / sponsor ID
- NCI-2012-01463
- Conditions
- Adult Acute Basophilic Leukemia, Adult Acute Eosinophilic Leukemia, Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monoblastic Leukemia (M5a), Adult Acute Monocytic Leukemia (M5b)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 74 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 Feb 2005 (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 and bortezomib in treating patients with relapsed or refractory hematologic cancer. 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. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving 17-N-allylamino-17-demethoxygeldanamycin together with bortezomib may kill more cancer cells.
Detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated dose (MTD) of PS-341 (Velcade, Bortezomib) in combination with 17-allyamino-17-demethoxygeldanamycin (17-AAG) in patients with relapsed or refractory acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL).
II. To determine the MTD of PS-341 in combination with 17-AAG in patients with relapsed or refractory chronic lymphocytic leukemia (CLL), and non-Hodgkin's lymphoma (NHL).
III. To define the specific toxicities and the dose limiting toxicity (DLT) of PS-341 in combination with 17-AAG in the treatment of patients with relapsed or refractory hematologic malignancies.
SECONDARY OBJECTIVES:
- To determine the pharmacokinetics of 17-AAG alone and in combination with PS-341 in patients with AML, ALL, CLL, and NHL.
II. To evaluate 20S proteasome inhibition following combination therapy with 17-AAG and PS-341 in patients with AML, ALL, CLL, and NHL.
III. To assess the relationship between FLT3 mutational status and leukemic cell response to PS-341 and 17-AAG in patients with AML.
IV. To assess the relationship between Bcl-2 over-expression and response to 17-AAG and PS-341 in patients with AML and NHL.
- To evaluate the effects of the combination of PS-341 and 17-AAG on Hsp90 and NF-kappaB and their downstream targets including Hsp70, Akt, phosphorylated Akt, p21, and caspases 3 and 9 in patient-derived primary AML and NHL cells.
OUTLINE: This is a dose-escalation study. Patients are stratified according to diagnosis (acute myeloid leukemia [AML] or acute lymphoblastic leukemia vs chronic lymphoctyic leukemia or non-Hodgkin's lymphoma [NHL]).
Patients receive 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) intravenously (IV) over 1-6 hours on days 1, 4, 8, and 11 and bortezomib IV over 3-5 seconds on days 4, 8, and 11 of course 1 and on days 1, 4, 8, and 11 of all subsequent courses.
Treatment repeats every 21 days for 3-12 courses provided patient is receiving clinical benefit. Patients achieving objective response may discontinue therapy to undergo stem cell transplantation.Cohorts of 3-6 patients with receive escalating doses of 17-AAG and bortezomib 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.
After the MTD is determined, an additional 20 patients (10 per stratum with AML or follicular NHL) are enrolled and receive 17-AAG and bortezomib as above at the MTD.
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-AAG and bortezomib) | Experimental | Drug: tanespimycin, Drug: bortezomibPatients receive 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) IV over 1-6 hours on days 1, 4, 8, and 11 and bortezomib IV over 3-5 seconds on days 4, 8, and 11 of course 1 and on days 1, 4, 8, and 11 of all subsequent courses. Treatment repeats every 21 days for 3-12 courses provided patient is receiving clinical benefit. Patients achieving objective response may discontinue therapy to undergo stem cell transplantation. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (78 listed)
- Histologically or cytologically confirmed diagnosis of 1 of the following hematologic malignancies:
- Patients with NHL or CLL must meet the following criteria:
- Relapsed or refractory disease
- Willing to undergo serial bone marrow biopsy (for patients enrolled after the MTD is determined)
- No untreated or active CNS leukemia or lymphoma
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-AAG and bortezomib) |
| bortezomibAlso: LDP 341, MLN341, VELCADEGiven IV | Drug | Treatment (17-AAG and bortezomib) |
Primary outcome
Maximum tolerated dose (MTD) of bortezomib) in combination with 17-AAG)
Time frame: Day 21
Defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
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.
- Derived from this study: PubMed 23256542Walker AR, Klisovic R, Johnston JS, Jiang Y, Geyer S, Kefauver C, Binkley P, Byrd JC, Grever MR, Garzon R, Phelps MA, Marcucci G, Blum KA, Blum W. Pharmacokinetics and dose escalation of the heat shock protein inhibitor 17-allyamino-17-demethoxygeldanamycin in combination with bortezomib in relapsed or refractory acute myeloid leukemia. Leuk Lymphoma. 2013 Sep;54(9):1996-2002. doi: 10.3109/10428194.2012.760733. Epub 2013 Jan 24.
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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.
Kristie Blum 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 bortezomib in people with Adult Acute Basophilic Leukemia and Adult Acute Eosinophilic 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 78 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 bortezomib) in combination with 17-AAG) (time frame: Day 21). 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 NCT00103272, 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 4 Jun 2013; AzTrials last refreshed its copy on 8 Nov 2026.