Hematologic MalignanciesPhase 1NCT00521859
Cloretazine (VNP40101M) With Hematopoietic Cell Transplantation for Hematologic Malignancies
A Phase 1 study testing Cloretazine and Fludarabine in people with Hematologic Malignancies, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
Primary: Define the maximal tolerated dose (MTD) of VNP40401M when given with hematopoietic cell transplantation (HCT) Secondary: Describe the change in pharmacokinetic (PK) parameters with increasing doses of drug. Describe and estimate the frequency of > Grade 3 non-hematologic/non-infectious toxicities at the MTD. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hematologic Malignancies
- What is being tested?
- Cloretazine and Fludarabine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2007to Dec 2010
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 to 65 years for autotransplant patients and age 18 to 60 years for allotransplant patients.
- Patients with acute leukemia/MDS or lymphoid malignancies, including Hodgkin's and non-Hodgkin's lymphoma (primary refractory or refractory relapse), or multiple myeloma (beyond first remission or unresponsive to therapy), not qualifying for treatment protocols of higher priority.
- Adequate renal function, as defined by serum creatinine <1.5 mg/dL.
- Adequate hepatic function, as defined by SGPT <3 X upper limit of normal; serum bilirubin and alkaline phosphatase <2 X upper limit of normal, or considered not attributable to liver disease in the case of alkaline phosphatase.
- Adequate pulmonary function with FEV1, FVC and DLCO >50% of expected corrected for hemoglobin.
- Adequate cardiac function with left ventricular ejection fraction >40%. No uncontrolled arrhythmias or symptomatic cardiac disease.
- Zubrod performance status <2
- Patients receiving an allogeneic transplant must have a related or unrelated donor which meets departmental standards for donor selection.
Who cannot join
- Uncontrolled life-threatening infections
- HIV positive
- A positive Beta HCG in a woman with child bearing potential as defined as not being post-menopausal for 12 or more months or no previous surgical sterilization procedures.
- Any CNS involvement which has not been controlled for at least 4 weeks
- Patients must be at least 21 days from prior systemic therapy for their malignancy, or have improvement of all reversible toxicities to </= grade 2, whichever occurs first.
- Any patient receiving Antabuse
- Patients should be off metronidazole (Flagyl) for at least 24 hours prior to starting VNP40401M
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Dose Escalation Trial of Cloretazine (VNP40101M) and Hematopoietic Cell Transplantation for Patients With Selected, Poor-Prognosis Hematologic Malignancies
Primary:
Define the maximal tolerated dose (MTD) of VNP40401M when given with hematopoietic cell transplantation (HCT)
Secondary:
- Describe the change in pharmacokinetic (PK) parameters with increasing doses of drug.
- Describe and estimate the frequency of > Grade 3 non-hematologic/non-infectious toxicities at the MTD.
- Report the efficacy of the regimen.
- Evaluate the rate of engraftment for the regimen.
Read the detailed description
An autologous transplant uses the recipient's own stem cells, from the blood and bone marrow, for infusion.
VNP40101M is a chemotherapy drug designed to interfere with the growth and development of cancer cells, by binding to structures within cancer cells. This drug, given in higher doses, causes lowering of blood cells. Chemotherapy is commonly given to patients before a stem cell transplantation to help kill more cancer cells. After receiving this drug, stem cells are transfused (given gradually) to allow re-growth of the blood cells.
Before you can start treatment on this study, you will have what are called "screening tests." These tests will help the doctor decide if you are eligible to take part in this study. You will have blood drawn (about 3 tablespoons) for routine tests. You will have a physical exam, including measurement of your vital signs (blood pressure, heart rate, temperature, and breathing rate). You will have a bone marrow biopsy. To collect a bone marrow biopsy, an area of the hip or chest bone is numbed with anesthetic, and a small amount of marrow and bone is withdrawn through a large needle. You will have a chest x-ray and computed tomography (CT) and positron emission tomography (PET) scans, if required, to measure your tumor. You will have a lung function test and an electrocardiogram (ECG-a test to measure the electrical activity of the heart). Women who are able to have children must have a negative blood or urine pregnancy test. If you will have a blood pregnancy test it will be done with routine blood tests.
Before you receive treatment on this study, you will have apheresis done to collect some of your stem cells. Apheresis is the process of removing part of the blood (such as platelets or white blood cells) from the body in order to remove certain elements, such as stem cells. Then the rest of the blood is returned back to the body. Your stem cells will be put back in your body after you finish treatment with VNP40101M. Apheresis will be done by a major vein through a central venous catheter (CVC), usually in the chest. A CVC is a sterile flexible tube that will be placed into a large vein while you are under local anesthesia. The details of apheresis as well as the CVC will be described in separate consent forms. Your doctor will explain these procedures to you in more detail, and you will be required to sign a separate consent form for each procedure.
If you are found to be eligible to take part in this study, you will receive a dose of VNP40101M. The dose you receive will depend on when you enrolled in this study. The dose that you receive will remain the same throughout this study. Researchers will continue to enroll patients at the next highest dose level until the highest tolerable dose is found.
About 1 week after your stem cells are collected, you will be admitted to the hospital. You will stay in the hospital for about 3 weeks. You will then receive VNP40101M by a CVC over 6 hours.
Two days after you receive VNP40101M, the autologous stem cells (blood or bone marrow) will then be given to you by your CVC. You will receive G-CSF as an injection just under your skin daily, starting 1 week after your transplantation, which will help your blood cell levels return to normal.
You will then have blood drawn (about 5 tablespoons) for PK testing to measure the levels of VNP40101M in your blood. These samples will be drawn through a heparin lock, which will be in place for 24 hours after the study treatment is complete. A heparin lock is a small tube connected to a CVC in a vein in the arm for easy access. The heparin lock will be removed after these samples are received.
After you are released from the hospital, you will be required to stay in the Houston area for up to 1 month after the transplantation or until you are no longer experiencing any intolerable side effects. You will be asked to return to M. D. Anderson between 2-4 months following transplantation so that any late side effects of the study drug can be observed.
As part of standard care, you will have blood tests (about 3 tablespoons) for routine tests. Your health status will be followed-up to continue to check on the status of the disease. You will have a computed tomography scan and PET scan. You will also have a bone marrow biopsy.
If the disease gets worse or you experience any intolerable side effects, you will be taken off this study.
THIS IS AN INVESTIGATIONAL STUDY. VNP40101M is not FDA approved or commercially available. It is authorized for use in research only.
Up to 42 patients will take part in this study. All will be enrolled at M. D. Anderson.
- Conditions
- Hematologic Malignancies
- Being tested
- Cloretazine, Fludarabine
- Keywords
- Hematologic Malignancies, Leukemia, Lymphoma, Myeloma, Hodgkin's Disease, Hematopoietic Cell Transplantation, Cloretazine, VNP40101M, Fludarabine, Fludarabine Phosphate, Fludara, ATG, Antithymocyte, Thymoglobulin
- Medical subject headings
- Hematologic Neoplasms, Leukemia, Lymphoma, Neoplasms, Plasma Cell, Hodgkin Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CloretazineDrug
Also called VNP40101M
800 mg/m^2 by vein daily
FludarabineDrug
Also called Fludarabine Phosphate, Fludara
25 mg/m^2 by vein daily x 5 Days
| Study group | Role | What they receive |
|---|---|---|
| Cloretazine + Fludarabine | Experimental | Not described Receives: Drug: Cloretazine; Drug: Fludarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
To study the highest tolerable dose of VNP40101M that can be given to patients with a form of leukemia, MDS, lymphoma, or myeloma in preparation for an autologous stem cell transplant.
Measured: 2 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2007 (estimated)
- Study startAug 2007
- Primary completionDec 2010
- Study completionDec 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hematologic MalignanciesStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Vion Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Roy B. Jones, MD, PhD, Principal investigator, UT MD Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00521859
- Sponsor's protocol ID
- 2005-0844
- Status last verified
- Jul 2012
- First submitted
- 27 Aug 2007
- Last updated
- 31 Jul 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dose Escalation Trial of Cloretazine (VNP40101M) and Hematopoietic Cell Transplantation for Patients With Selected, Poor-Prognosis Hematologic Malignancies
- ClinicalTrials.gov ID
- NCT00521859
- Acronym / sponsor ID
- 2005-0844
- Conditions
- Hematologic Malignancies
- Keywords
- Hematologic Malignancies, Leukemia, Lymphoma, Myeloma, Hodgkin's Disease, Hematopoietic Cell Transplantation, Cloretazine, VNP40101M
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Vion Pharmaceuticals
- Study start
- Aug 2007
- Primary completion
- Dec 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 28 Aug 2007 (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.
Primary:
Define the maximal tolerated dose (MTD) of VNP40401M when given with hematopoietic cell transplantation (HCT)
Secondary:
- Describe the change in pharmacokinetic (PK) parameters with increasing doses of drug.
- Describe and estimate the frequency of > Grade 3 non-hematologic/non-infectious toxicities at the MTD.
- Report the efficacy of the regimen.
- Evaluate the rate of engraftment for the regimen.
Detailed description
An autologous transplant uses the recipient's own stem cells, from the blood and bone marrow, for infusion.
VNP40101M is a chemotherapy drug designed to interfere with the growth and development of cancer cells, by binding to structures within cancer cells. This drug, given in higher doses, causes lowering of blood cells. Chemotherapy is commonly given to patients before a stem cell transplantation to help kill more cancer cells. After receiving this drug, stem cells are transfused (given gradually) to allow re-growth of the blood cells.
Before you can start treatment on this study, you will have what are called "screening tests." These tests will help the doctor decide if you are eligible to take part in this study. You will have blood drawn (about 3 tablespoons) for routine tests. You will have a physical exam, including measurement of your vital signs (blood pressure, heart rate, temperature, and breathing rate). You will have a bone marrow biopsy. To collect a bone marrow biopsy, an area of the hip or chest bone is numbed with anesthetic, and a small amount of marrow and bone is withdrawn through a large needle. You will have a chest x-ray and computed tomography (CT) and positron emission tomography (PET) scans, if required, to measure your tumor. You will have a lung function test and an electrocardiogram (ECG-a test to measure the electrical activity of the heart). Women who are able to have children must have a negative blood or urine pregnancy test. If you will have a blood pregnancy test it will be done with routine blood tests.
Before you receive treatment on this study, you will have apheresis done to collect some of your stem cells. Apheresis is the process of removing part of the blood (such as platelets or white blood cells) from the body in order to remove certain elements, such as stem cells. Then the rest of the blood is returned back to the body. Your stem cells will be put back in your body after you finish treatment with VNP40101M. Apheresis will be done by a major vein through a central venous catheter (CVC), usually in the chest. A CVC is a sterile flexible tube that will be placed into a large vein while you are under local anesthesia. The details of apheresis as well as the CVC will be described in separate consent forms. Your doctor will explain these procedures to you in more detail, and you will be required to sign a separate consent form for each procedure.
If you are found to be eligible to take part in this study, you will receive a dose of VNP40101M. The dose you receive will depend on when you enrolled in this study. The dose that you receive will remain the same throughout this study. Researchers will continue to enroll patients at the next highest dose level until the highest tolerable dose is found.
About 1 week after your stem cells are collected, you will be admitted to the hospital. You will stay in the hospital for about 3 weeks. You will then receive VNP40101M by a CVC over 6 hours.
Two days after you receive VNP40101M, the autologous stem cells (blood or bone marrow) will then be given to you by your CVC. You will receive G-CSF as an injection just under your skin daily, starting 1 week after your transplantation, which will help your blood cell levels return to normal.
You will then have blood drawn (about 5 tablespoons) for PK testing to measure the levels of VNP40101M in your blood. These samples will be drawn through a heparin lock, which will be in place for 24 hours after the study treatment is complete. A heparin lock is a small tube connected to a CVC in a vein in the arm for easy access. The heparin lock will be removed after these samples are received.
After you are released from the hospital, you will be required to stay in the Houston area for up to 1 month after the transplantation or until you are no longer experiencing any intolerable side effects. You will be asked to return to M. D. Anderson between 2-4 months following transplantation so that any late side effects of the study drug can be observed.
As part of standard care, you will have blood tests (about 3 tablespoons) for routine tests. Your health status will be followed-up to continue to check on the status of the disease. You will have a computed tomography scan and PET scan. You will also have a bone marrow biopsy.
If the disease gets worse or you experience any intolerable side effects, you will be taken off this study.
THIS IS AN INVESTIGATIONAL STUDY. VNP40101M is not FDA approved or commercially available. It is authorized for use in research only.
Up to 42 patients will take part in this study. All will be enrolled at M. D. Anderson.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cloretazine + Fludarabine | Experimental | Drug: Cloretazine, Drug: Fludarabine |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age 18 to 65 years for autotransplant patients and age 18 to 60 years for allotransplant patients.
- Patients with acute leukemia/MDS or lymphoid malignancies, including Hodgkin's and non-Hodgkin's lymphoma (primary refractory or refractory relapse), or multiple myeloma (beyond first remission or unresponsive to therapy), not qualifying for treatment protocols of higher priority.
- Adequate renal function, as defined by serum creatinine <1.5 mg/dL.
- Adequate hepatic function, as defined by SGPT <3 X upper limit of normal; serum bilirubin and alkaline phosphatase <2 X upper limit of normal, or considered not attributable to liver disease in the case of alkaline phosphatase.
- Adequate pulmonary function with FEV1, FVC and DLCO >50% of expected corrected for hemoglobin.
Key exclusion criteria (7 listed)
- Uncontrolled life-threatening infections
- HIV positive
- A positive Beta HCG in a woman with child bearing potential as defined as not being post-menopausal for 12 or more months or no previous surgical sterilization procedures.
- Any CNS involvement which has not been controlled for at least 4 weeks
- Patients must be at least 21 days from prior systemic therapy for their malignancy, or have improvement of all reversible toxicities to </= grade 2, whichever occurs first.
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 |
|---|---|---|
| CloretazineAlso: VNP40101M800 mg/m^2 by vein daily | Drug | Cloretazine + Fludarabine |
| FludarabineAlso: Fludarabine Phosphate, Fludara25 mg/m^2 by vein daily x 5 Days | Drug | Cloretazine + Fludarabine |
Primary outcome
To study the highest tolerable dose of VNP40101M that can be given to patients with a form of leukemia, MDS, lymphoma, or myeloma in preparation for an autologous stem cell transplant.
Time frame: 2 Years
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 31 Jul 2012.
- UT MD Anderson Cancer CenterLink provided by the sponsor.
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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.
Roy B. Jones, MD, PhD principal investigator
UT MD Anderson Cancer Center
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 Cloretazine and Fludarabine in people with Hematologic Malignancies, run by M.D. Anderson Cancer Center 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 8 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: finished, as of the sponsor's last update on 31 Jul 2012. 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 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?
To study the highest tolerable dose of VNP40101M that can be given to patients with a form of leukemia, MDS, lymphoma, or myeloma in preparation for an autologous stem cell transplant. (time frame: 2 Years). 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 31 Jul 2012.