LeukemiaPhase 1NCT01094860
Pharmacokinetic (PK) and Pharmacodynamic (PD) Study of Nelarabine in Patients With Relapsed/Refractory Lymphoid Malignancies
A Phase 1 study testing Nelarabine in people with Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
The goal of the clinical research study is to find the highest tolerable dose of nelarabine when given as a continuous infusion to patients with a lymphoid malignancy that has not responded to, or has come back after treatment with chemotherapy. The safety of this drug will also be studied. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Leukemia
- What is being tested?
- Nelarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Jun 2010to 9 Aug 2018
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients must have one of the following relapsed/ refractory lymphoid malignancies: Chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL) or B-prolymphocytic leukemia which has been previously treated with a purine analog, and are not candidates for higher priority clinical studies. Follicular lymphoma, mantle cell lymphoma, lymphoplasmacytoid lymphoma or marginal zone lymphoma which has been previously treated with autologous or allogeneic stem cell transplantation.
- Continued from #1:T-cell prolymphocytic leukemia, large granular lymphocyte leukemia, mycosis fungoides / Sezary syndrome or peripheral T-cell lymphoma which has been previously treated with at least one line of chemotherapy or monoclonal antibody therapy. T-cell or B-cell acute lymphoblastic leukemia (ALL) which has been previously treated with at least one line of chemotherapy.
- Patients (both pediatrics and adults) must have adequate renal function (calculated creatinine clearance >/= 50ml/min). For adults this will be calculated per the Cockcroft -Gault formula and in pediatric cases this will be calculated per the Schwartz formula.
- Patients must have adequate hepatic function (bilirubin </= 2 mg/dL; SGOT or SGPT </= 3X the ULN for the reference lab unless due to leukemia).
- Patients must have adequate marrow function (neutrophils >/= 0.5x10^9/L and platelets >/= 50x10^9/L) unless cytopenias are deemed due to disease.
- Patients must have adequate performance status (Zubrod 0-2).
- Female patients must not be pregnant or lactating. Female patients of childbearing potential (including those <1 year postmenopausal) and male patients must agree to use contraception.
- Patients must sign an informed consent form indicating that they are aware of the investigational nature of this study, in keeping with the policies of the hospital.
Who cannot join
- Patients must not have untreated or uncontrolled life-threatening infection.
- Patients known to be HIV positive or known to have Hepatitis B and/or C are excluded.
- Patients must not have received systemic chemotherapy or monoclonal antibody therapy within 2 weeks of study enrollment. Patients who have previously received bolus nelarabine are still eligible. Hydroxyurea or corticosteroids for control of blood counts is allowed, but must be discontinued 24 hours prior to initiating nelarabine.
- Patients must not have a history of grade >/=2 neurological toxicity with previous treatment, or persistent grade >/=2 peripheral neuropathy. Drowsiness and lethargy were exempted from this criteria unless previously persistent for more than one week.
- Patients must not have uncontrolled central nervous system disease. Patients with a history of seizure disorders must be seizure-free for one year prior to enrolment.
- Patients must not have any other medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a patient's ability to give informed consent or cooperate and participate in the study or interfere with the interpretation of the results.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: A Pharmacokinetic and Pharmacodynamic Study to Evaluate the Safety and Feasibility of Continuous Infusion Nelarabine in Patients With Relapsed / Refractory Lymphoid Malignancies
The goal of the clinical research study is to find the highest tolerable dose of nelarabine when given as a continuous infusion to patients with a lymphoid malignancy that has not responded to, or has come back after treatment with chemotherapy. The safety of this drug will also be studied.
Read the detailed description
The Study Drug:
Nelarabine is designed to interfere with DNA (the genetic material of cells) and stop the growth of rapidly dividing cells, such as cancer cells.
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a dose level of nelarabine based on when you joined this study. Up to 8 dose levels of nelarabine will be tested. Three (3) to 6 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of nelarabine is found.
Study Drug Administration:
You will receive nelarabine as a non-stop infusion through a needle or catheter in your vein on Days 1-5 of each 4 - 6 week cycle. You will remain in the hospital for this infusion.
You may receive ondansetron or a similar drug by vein over about 30 minutes before you receive nelarabine. This is given to help prevent nausea. You will also take ondansetron or a similar drug by mouth every 12 hours for the next 7 days as needed. If you are still having nausea, you will be given additional drugs.
If you are not allergic, you may receive allopurinol by mouth on Days 1-10 of Cycles 1. Allopurinol is given to help reduce the risk of too much uric acid in the blood. If the level of uric acid in the blood is too high, you may receive additional drugs.
You may also be given drugs to help reduce the risk of infection.
Study Visits:
On Day 1 of Cycle 1 only, blood (about 2 teaspoons each time) will be drawn for pharmacokinetic (PK) and pharmacodynamic (PD) testing 1 hour before, then again 2, 4, 6, and between 10-18 hours after the study drug infusion. PK testing measures the amount of study drug in the body at different time points. PD testing measures how the level of study drug in your body may affect the disease
On Days 2, 3, 4, and 5 of Cycle 1 only, blood (about 2 teaspoons) will be drawn for PK and PD testing.
On Day 1 of each cycle:
- You will have a physical exam, including measurement of your vital signs.
- You will be asked about any drugs you are taking and about any transfusions you may have had.
- You will be asked about any side effects you may have had.
- Your performance status will be recorded.
- Measurements of your lymph nodes, spleen, and liver will be taken.
- Blood (about 2 teaspoons) will be drawn to test the levels of antibodies and T-cells (a type of white blood cell) in your blood.
One (1) time each week, or more often if the study doctor thinks it is needed:
- You will have a physical exam, including measurement of your vital signs.
- You will be asked about any side effects you may have had.
- Your performance status will be recorded.
- Blood (about 4 teaspoons) will be drawn for routine tests.
After every 3 cycles:
- You will have a physical exam, including measurement of your vital signs.
- You will be asked about any drugs you are taking and about any transfusions you may have had.
- You will be asked about any side effects you may have had.
- Your performance status will be recorded.
- Measurements of your lymph nodes, spleen, and liver will be taken.
- Blood (about 4 teaspoons) will be drawn for routine tests.
- You will have a neurological exam (tests to check the functioning of your nerves, including tests of your balance and reflexes).
- Blood (about 2 teaspoons) will be drawn to check the number of T-cells in your blood.
- You will have a bone marrow aspirate/biopsy to check the status of the disease.
- If you have NHL, you will have CT scan of the chest, abdomen, and pelvis to check the status of the disease.
Length of Participation:
You may continue to receive nelarabine for as long as the study doctor thinks it is in your best interest. You will no longer be able to receive the study drug if the disease gets worse or intolerable side effects occur.
This is an investigational study. Nelarabine, given as an injection, is FDA approved for the treatment of refractory or relapsed T-cell acute lymphoblastic leukemia or T lymphoblastic lymphoma. The use of nelarabine as a continuous infusion is investigational.
Up to 35 patients will take part in this study. All will be enrolled at MD Anderson.
- Conditions
- Leukemia
- Being tested
- Nelarabine
- Keywords
- Relapsed/Refractory Lymphoid Malignancies, Chronic lymphocytic leukemia, CLL, Small lymphocytic lymphoma, SLL, B-prolymphocytic leukemia, Follicular lymphoma, Mantle cell lymphoma, Lymphoplasmacytoid lymphoma, Marginal zone lymphoma, T-cell prolymphocytic leukemia, large granular lymphocyte leukemia, mycosis fungoides, Sezary syndrome, peripheral T-cell lymphoma, Chemotherapy, Monoclonal antibody therapy, T-cell or B-cell acute lymphoblastic leukemia (ALL), Continuous Infusion Nelarabine, Arranon
- Medical subject headings
- Leukemia, Recurrence, Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Prolymphocytic, B-Cell, Lymphoma, Follicular, Lymphoma, Mantle-Cell, Waldenstrom Macroglobulinemia, Lymphoma, B-Cell, Marginal Zone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NelarabineDrug
Also called Arranon
Starting dose 200 mg/m2 for 5 day continuous infusion administered via a central catheter, repeated every 28 days.
| Study group | Role | What they receive |
|---|---|---|
| Continuous Infusion Nelarabine | Experimental | Starting dose 200 mg/m2 x 5 days Receives: Drug: Nelarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of a 5-day Continuous Infusion Schedule of Nelarabine
MTD defined as the highest dose that no more than 1 dose limiting toxicity (DLT) occurs among 6 patients. Dose-limiting toxicity (DLT) defined based on drug related events only. DLT in the first treatment cycle used for the dose escalation.
Measured: 28 day cycle
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2010 (estimated)
- Study start8 Jun 2010
- Primary completion9 Aug 2018
- Study completion9 Aug 2018
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 LeukemiaStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- Tapan Kadia, MD, Study chair, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01094860
- Sponsor's protocol ID
- 2009-0717
- Other IDs
- NCI-2010-01659
- Status last verified
- Feb 2020
- First submitted
- 25 Mar 2010
- Last updated
- 11 Feb 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Boddu PC, Senapati J, Ravandi-Kashani F, Jabbour EJ, Jain N, Ayres M, Chen Y, Keating MJ, Kantarjian HM, Gandhi V, Kadia TM. A phase 1 study to evaluate the safety, pharmacology, and feasibility of continuous infusion nelarabine in patients with relapsed and/or refractory lymphoid malignancies. Cancer. 2023 Feb 15;129(4):580-589. doi: 10.1002/cncr.34570. Epub 2022 Nov 29.
PubMed 36448227
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pharmacokinetic and Pharmacodynamic Study to Evaluate the Safety and Feasibility of Continuous Infusion Nelarabine in Patients With Relapsed / Refractory Lymphoid Malignancies
- ClinicalTrials.gov ID
- NCT01094860
- Acronym / sponsor ID
- 2009-0717
- Conditions
- Leukemia
- Keywords
- Relapsed/Refractory Lymphoid Malignancies, Chronic lymphocytic leukemia, CLL, Small lymphocytic lymphoma, SLL, B-prolymphocytic leukemia, Follicular lymphoma, Mantle cell lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- GlaxoSmithKline
- Study start
- 8 Jun 2010 (actual)
- Primary completion
- 9 Aug 2018 (actual)
- Study completion
- 9 Aug 2018 (actual)
- First posted
- 29 Mar 2010 (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.
The goal of the clinical research study is to find the highest tolerable dose of nelarabine when given as a continuous infusion to patients with a lymphoid malignancy that has not responded to, or has come back after treatment with chemotherapy. The safety of this drug will also be studied.
Detailed description
The Study Drug:
Nelarabine is designed to interfere with DNA (the genetic material of cells) and stop the growth of rapidly dividing cells, such as cancer cells.
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a dose level of nelarabine based on when you joined this study. Up to 8 dose levels of nelarabine will be tested. Three (3) to 6 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of nelarabine is found.
Study Drug Administration:
You will receive nelarabine as a non-stop infusion through a needle or catheter in your vein on Days 1-5 of each 4 - 6 week cycle. You will remain in the hospital for this infusion.
You may receive ondansetron or a similar drug by vein over about 30 minutes before you receive nelarabine. This is given to help prevent nausea. You will also take ondansetron or a similar drug by mouth every 12 hours for the next 7 days as needed. If you are still having nausea, you will be given additional drugs.
If you are not allergic, you may receive allopurinol by mouth on Days 1-10 of Cycles 1. Allopurinol is given to help reduce the risk of too much uric acid in the blood. If the level of uric acid in the blood is too high, you may receive additional drugs.
You may also be given drugs to help reduce the risk of infection.
Study Visits:
On Day 1 of Cycle 1 only, blood (about 2 teaspoons each time) will be drawn for pharmacokinetic (PK) and pharmacodynamic (PD) testing 1 hour before, then again 2, 4, 6, and between 10-18 hours after the study drug infusion. PK testing measures the amount of study drug in the body at different time points. PD testing measures how the level of study drug in your body may affect the disease
On Days 2, 3, 4, and 5 of Cycle 1 only, blood (about 2 teaspoons) will be drawn for PK and PD testing.
On Day 1 of each cycle:
- You will have a physical exam, including measurement of your vital signs.
- You will be asked about any drugs you are taking and about any transfusions you may have had.
- You will be asked about any side effects you may have had.
- Your performance status will be recorded.
- Measurements of your lymph nodes, spleen, and liver will be taken.
- Blood (about 2 teaspoons) will be drawn to test the levels of antibodies and T-cells (a type of white blood cell) in your blood.
One (1) time each week, or more often if the study doctor thinks it is needed:
- You will have a physical exam, including measurement of your vital signs.
- You will be asked about any side effects you may have had.
- Your performance status will be recorded.
- Blood (about 4 teaspoons) will be drawn for routine tests.
After every 3 cycles:
- You will have a physical exam, including measurement of your vital signs.
- You will be asked about any drugs you are taking and about any transfusions you may have had.
- You will be asked about any side effects you may have had.
- Your performance status will be recorded.
- Measurements of your lymph nodes, spleen, and liver will be taken.
- Blood (about 4 teaspoons) will be drawn for routine tests.
- You will have a neurological exam (tests to check the functioning of your nerves, including tests of your balance and reflexes).
- Blood (about 2 teaspoons) will be drawn to check the number of T-cells in your blood.
- You will have a bone marrow aspirate/biopsy to check the status of the disease.
- If you have NHL, you will have CT scan of the chest, abdomen, and pelvis to check the status of the disease.
Length of Participation:
You may continue to receive nelarabine for as long as the study doctor thinks it is in your best interest. You will no longer be able to receive the study drug if the disease gets worse or intolerable side effects occur.
This is an investigational study. Nelarabine, given as an injection, is FDA approved for the treatment of refractory or relapsed T-cell acute lymphoblastic leukemia or T lymphoblastic lymphoma. The use of nelarabine as a continuous infusion is investigational.
Up to 35 patients will take part in this study. All will be enrolled at MD Anderson.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Continuous Infusion Nelarabine | Experimental | Drug: NelarabineStarting dose 200 mg/m2 x 5 days |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Patients must have one of the following relapsed/ refractory lymphoid malignancies: Chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL) or B-prolymphocytic leukemia which has been previously treated with a purine analog, and are not candidates for higher priority clinical studies. Follicular lymphoma, mantle cell lymphoma, lymphoplasmacytoid lymphoma or marginal zone lymphoma which has been previously treated with autologous or allogeneic stem cell transplantation.
- Continued from #1:T-cell prolymphocytic leukemia, large granular lymphocyte leukemia, mycosis fungoides / Sezary syndrome or peripheral T-cell lymphoma which has been previously treated with at least one line of chemotherapy or monoclonal antibody therapy. T-cell or B-cell acute lymphoblastic leukemia (ALL) which has been previously treated with at least one line of chemotherapy.
- Patients (both pediatrics and adults) must have adequate renal function (calculated creatinine clearance >/= 50ml/min). For adults this will be calculated per the Cockcroft -Gault formula and in pediatric cases this will be calculated per the Schwartz formula.
- Patients must have adequate hepatic function (bilirubin </= 2 mg/dL; SGOT or SGPT </= 3X the ULN for the reference lab unless due to leukemia).
- Patients must have adequate marrow function (neutrophils >/= 0.5x10^9/L and platelets >/= 50x10^9/L) unless cytopenias are deemed due to disease.
Key exclusion criteria (6 listed)
- Patients must not have untreated or uncontrolled life-threatening infection.
- Patients known to be HIV positive or known to have Hepatitis B and/or C are excluded.
- Patients must not have received systemic chemotherapy or monoclonal antibody therapy within 2 weeks of study enrollment. Patients who have previously received bolus nelarabine are still eligible. Hydroxyurea or corticosteroids for control of blood counts is allowed, but must be discontinued 24 hours prior to initiating nelarabine.
- Patients must not have a history of grade >/=2 neurological toxicity with previous treatment, or persistent grade >/=2 peripheral neuropathy. Drowsiness and lethargy were exempted from this criteria unless previously persistent for more than one week.
- Patients must not have uncontrolled central nervous system disease. Patients with a history of seizure disorders must be seizure-free for one year prior to enrolment.
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 |
|---|---|---|
| NelarabineAlso: ArranonStarting dose 200 mg/m2 for 5 day continuous infusion administered via a central catheter, repeated every 28 days. | Drug | Continuous Infusion Nelarabine |
Primary outcome
Maximum Tolerated Dose (MTD) of a 5-day Continuous Infusion Schedule of Nelarabine
Time frame: 28 day cycle
MTD defined as the highest dose that no more than 1 dose limiting toxicity (DLT) occurs among 6 patients. Dose-limiting toxicity (DLT) defined based on drug related events only. DLT in the first treatment cycle used for the dose escalation.
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 11 Feb 2020.
- Derived from this study: PubMed 36448227Boddu PC, Senapati J, Ravandi-Kashani F, Jabbour EJ, Jain N, Ayres M, Chen Y, Keating MJ, Kantarjian HM, Gandhi V, Kadia TM. A phase 1 study to evaluate the safety, pharmacology, and feasibility of continuous infusion nelarabine in patients with relapsed and/or refractory lymphoid malignancies. Cancer. 2023 Feb 15;129(4):580-589. doi: 10.1002/cncr.34570. Epub 2022 Nov 29.
- University of Texas MD Anderson Cancer Center WebsiteLink 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.
Tapan Kadia, MD study chair
M.D. 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 Nelarabine in people with Leukemia, 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 6 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 11 Feb 2020. 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?
Maximum Tolerated Dose (MTD) of a 5-day Continuous Infusion Schedule of Nelarabine (time frame: 28 day cycle). 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 NCT01094860, 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 11 Feb 2020.