LeukemiaPhase 2NCT00083187
VNP40101M in Treating Patients With Acute Myelogenous Leukemia or High-Risk Myelodysplasia
A Phase 2 study testing hydroxyurea and laromustine in people with Leukemia and Myelodysplastic Syndromes, run by Vion Pharmaceuticals at 5 sites in 3 countries.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as VNP40101M and hydroxyurea, work in different ways to stop cancer cells from dividing so they stop growing or die. Hydroxyurea may help VNP40101M kill more cancer cells by making cancer cells more sensitive to the drug. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms
- What is being tested?
- hydroxyurea and laromustine
- How many people
- 230 participants
- Where
- 5 sitesin 3 countries
- Study dates
- Nov 2005to Aug 2008
- Phase
- Phase 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically confirmed diagnosis of 1 of the following:
- Acute myelogenous leukemia (AML), meeting the following criteria:
- In first relapse after first treatment-induced complete remission (CR) (closed to accrual as of 06/09/05)
- Duration of first CR less than 12 months
- No prior treatment for first relapse except hydroxyurea
- FAB type M0, M1, M2, M4-7
- No acute promyelocytic leukemia
- No prior treatment with a standard induction regimen containing cytotoxic agents* (for patients 60 years of age or older)
- High-risk myelodysplasia, meeting the following criteria:
- 60 years of age and over
- No prior cytotoxic chemotherapy* except hydroxyurea
- Prior gemtuzumab ozogamicin allowed
- High risk defined as International Prognostic Scoring System score ≥ 1.5, defined by cytogenetics, % marrow blasts, and lineage cytopenias NOTE: *Prior low-dose, single-agent cytarabine, decitabine, or azacitidine not considered prior cytotoxic chemotherapy
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0-2
Life expectancy
- Not specified
Hematopoietic
- Not specified
Hepatic
- Bilirubin ≤ 2.0 mg/dL
- ALT or AST ≤ 5 times upper limit of normal
- Chronic hepatitis allowed
Renal
- Creatinine ≤ 2.0 mg/dL
Cardiovascular
- No myocardial infarction within the past 3 months
- No symptomatic coronary artery disease
- No uncontrolled arrhythmias
- No uncontrolled congestive heart failure
- No other active heart disease
Other
- No uncontrolled active infection
- Not pregnant or nursing
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Up to 4 leukapheresis procedures allowed during the first 15 days of study treatment
Chemotherapy
- See Disease Characteristics
- Concurrent additional hydroxyurea (maximum dose of 5 g daily for up to 4 days) allowed between days 4 and 15 of each study course to control elevated blast levels
Endocrine therapy
- Not specified
Radiotherapy
- Not specified
Surgery
- Not specified
Other
- Recovered from all prior therapy
- At least 72 hours since prior anti-leukemic treatment with a non-cytotoxic agent
- No concurrent disulfiram (Antabuse)
- No other concurrent anticancer drugs except anagrelide within the first 15 days of study treatment to control elevated platelet counts
- No other concurrent treatment for leukemia, except hydroxyurea used during study treatment
- No other concurrent investigational drugs
Trial locations and contacts
5 sites in 3 countries.
5 sites in 3 countries
United States3 sites
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, 21231
Duke Comprehensive Cancer Center
Durham, North Carolina, 27710
M.D. Anderson Cancer Center at University of Texas
Houston, Texas, 77030-4009
France1 site
Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes
Marseille, 13273
About this study
Official title: A Phase II Study of VNP40101M For Patients With Acute Myelogenous Leukemia Or High-Risk Myelodysplasia
RATIONALE: Drugs used in chemotherapy, such as VNP40101M and hydroxyurea, work in different ways to stop cancer cells from dividing so they stop growing or die. Hydroxyurea may help VNP40101M kill more cancer cells by making cancer cells more sensitive to the drug.
PURPOSE: This phase II trial is studying how well giving VNP40101M with hydroxyurea works in treating patients with acute myelogenous leukemia or high-risk myelodysplasia.
Read the detailed description
OBJECTIVES:
- Determine the complete response rate to VNP40101M in patients with acute myelogenous leukemia or high-risk myelodysplasia .
- Determine the toxic effects of this regimen in these patients.
- Determine the pharmacokinetics of this regimen in these patients.
OUTLINE: This is an open-label, multicenter study. Patients are stratified to acute myelogenous leukemia (AML) or high risk myelodysplasia (MDS) patients ≥ 60 years old with no prior treatment vs AML patients any age in first relapse. (AML patients any age in first relapse closed to accrual 06/09/05).
Patients receive VNP40101M IV over 30 minutes once on day 1 (course 1).
Four to five weeks after the first course, patients undergo bone marrow aspiration and biopsy. If the bone marrow is improved but contains residual leukemia, patients receive a second course of VNP40101M (at the same dose as in course 1). If patients achieve complete response (CR), or partial CR after the first or second course, a consolidation course may be given comprising VNP40101M at a reduced dose.
Patients are followed monthly for 6 months, every 2 months for 12 months, and then every 3 months for 18 months .
PROJECTED ACCRUAL: A total of 230 patients (100 with acute myelogenous leukemia (AML) or high-risk myelodysplasia and 130 with AML in first relapse) will be accrued for this study.
- Being tested
- hydroxyurea, laromustine
- Keywords
- recurrent adult acute myeloid leukemia, untreated adult acute myeloid leukemia, atypical chronic myeloid leukemia, BCR-ABL1 negative, chronic myelomonocytic leukemia, myelodysplastic/myeloproliferative neoplasm, unclassifiable, secondary myelodysplastic syndromes, de novo myelodysplastic syndromes, adult acute myeloid leukemia with t(8;21)(q22;q22), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with t(15;17)(q22;q12)
- Medical subject headings
- Leukemia, Myelodysplastic Syndromes, Myelodysplastic-Myeloproliferative Diseases, Leukemia, Myeloid, Acute, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative, Leukemia, Myelomonocytic, Chronic, Myeloproliferative Disorders, Congenital Abnormalities
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
hydroxyureaDrug
laromustineDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete response rate
Toxic effects
Pharmacokinetics
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2004 (estimated)
- Study startNov 2005
- Primary completionJan 2007
- Study completionAug 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Masking
- None (open label)
- Enrolment
- 230 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Vion Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Francis J. Giles, MD, Study chair, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00083187
- Sponsor's protocol ID
- VION-CLI-033
- Other IDs
- CDR0000365510
- Status last verified
- Aug 2008
- First submitted
- 14 May 2004
- Last updated
- 18 Jul 2013
- Results posted
- No
Publications
Gerson SL, Karp J, Rizzieri D, et al.: Low levels of pre-treatment O6-alkylguanine transferase (AGT) in patients with AML correlate with response to Cloretazine® (VNP40101M) induction therapy. [Abstract] American Association for Cancer Research: 98th Annual Meeting, April 14-18, 2007, Los Angeles, CA. A-2640, 2007.
Giles F, Rizzieri D, Karp J, Vey N, Ravandi F, Faderl S, Khan KD, Verhoef G, Wijermans P, Advani A, Roboz G, Kantarjian H, Bilgrami SF, Ferrant A, Daenen SM, Karsten V, Cahill A, Albitar M, Mufti G, O'Brien S. Cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent, in patients age 60 years or older with previously untreated acute myeloid leukemia. J Clin Oncol. 2007 Jan 1;25(1):25-31. doi: 10.1200/JCO.2006.07.0961. Epub 2006 Dec 4.
PubMed 17146105
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of VNP40101M For Patients With Acute Myelogenous Leukemia Or High-Risk Myelodysplasia
- ClinicalTrials.gov ID
- NCT00083187
- Acronym / sponsor ID
- VION-CLI-033
- Keywords
- recurrent adult acute myeloid leukemia, untreated adult acute myeloid leukemia, atypical chronic myeloid leukemia, BCR-ABL1 negative, chronic myelomonocytic leukemia, myelodysplastic/myeloproliferative neoplasm, unclassifiable, secondary myelodysplastic syndromes, de novo myelodysplastic syndromes, adult acute myeloid leukemia with t(8;21)(q22;q22)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 230 participants (estimated)
- Lead sponsor
- Vion PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Nov 2005
- Primary completion
- Jan 2007 (actual)
- Study completion
- Aug 2008 (actual)
- First posted
- 17 May 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.
RATIONALE: Drugs used in chemotherapy, such as VNP40101M and hydroxyurea, work in different ways to stop cancer cells from dividing so they stop growing or die. Hydroxyurea may help VNP40101M kill more cancer cells by making cancer cells more sensitive to the drug.
PURPOSE: This phase II trial is studying how well giving VNP40101M with hydroxyurea works in treating patients with acute myelogenous leukemia or high-risk myelodysplasia.
Detailed description
OBJECTIVES:
- Determine the complete response rate to VNP40101M in patients with acute myelogenous leukemia or high-risk myelodysplasia .
- Determine the toxic effects of this regimen in these patients.
- Determine the pharmacokinetics of this regimen in these patients.
OUTLINE: This is an open-label, multicenter study. Patients are stratified to acute myelogenous leukemia (AML) or high risk myelodysplasia (MDS) patients ≥ 60 years old with no prior treatment vs AML patients any age in first relapse. (AML patients any age in first relapse closed to accrual 06/09/05).
Patients receive VNP40101M IV over 30 minutes once on day 1 (course 1).
Four to five weeks after the first course, patients undergo bone marrow aspiration and biopsy. If the bone marrow is improved but contains residual leukemia, patients receive a second course of VNP40101M (at the same dose as in course 1). If patients achieve complete response (CR), or partial CR after the first or second course, a consolidation course may be given comprising VNP40101M at a reduced dose.
Patients are followed monthly for 6 months, every 2 months for 12 months, and then every 3 months for 18 months .
PROJECTED ACCRUAL: A total of 230 patients (100 with acute myelogenous leukemia (AML) or high-risk myelodysplasia and 130 with AML in first relapse) will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| hydroxyurea | Drug | – |
| laromustine | Drug | – |
Primary outcome
Complete response rate
Toxic effects
Pharmacokinetics
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2013.
- Results publicationGerson SL, Karp J, Rizzieri D, et al.: Low levels of pre-treatment O6-alkylguanine transferase (AGT) in patients with AML correlate with response to Cloretazine® (VNP40101M) induction therapy. [Abstract] American Association for Cancer Research: 98th Annual Meeting, April 14-18, 2007, Los Angeles, CA. A-2640, 2007.
- Results publication: PubMed 17146105Giles F, Rizzieri D, Karp J, Vey N, Ravandi F, Faderl S, Khan KD, Verhoef G, Wijermans P, Advani A, Roboz G, Kantarjian H, Bilgrami SF, Ferrant A, Daenen SM, Karsten V, Cahill A, Albitar M, Mufti G, O'Brien S. Cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent, in patients age 60 years or older with previously untreated acute myeloid leukemia. J Clin Oncol. 2007 Jan 1;25(1):25-31. doi: 10.1200/JCO.2006.07.0961. Epub 2006 Dec 4.
Related trials for Leukemia
RecruitingPhase 2
Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 1
A Study of CHM-029 in Participants With NPM1 Mutated, KMT2A or NUP98 Rearranged AML
AML (Acute Myeloid Leukemia)
RecruitingPhase 1
Vididencel in CML-CP Patients With MRD
CML (Chronic Myelogenous Leukemia)
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
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.
Francis J. Giles, MD study chair
M.D. Anderson Cancer Center
5 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing hydroxyurea and laromustine in people with Leukemia and Myelodysplastic Syndromes, run by Vion Pharmaceuticals at 5 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 18 Jul 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, France, United Kingdom. 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 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 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?
Complete response rate. 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 NCT00083187, which also lists 2 linked publications.
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 18 Jul 2013.