LymphomaPhase 1NCT01049113
Safety Study of ON 013105 in Lymphoma and Acute Lymphoid Leukemia
A Phase 1 study testing ON 013105 in people with Lymphoma and Acute Lymphocytic Leukemia, run by Traws Pharma, Inc. at 1 site in United States.
Trial summary
This is an open-label, dose-escalation Phase 1 study of the investigational agent, ON 013105. In laboratory animal studies, ON 013105 has demonstrated anti-cancer activity. The purpose of this study is to determine the highest dose of ON 013105 that can be given safely in patients with relapsed/refractory Lymphoma or… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma, Acute Lymphocytic Leukemia
- What is being tested?
- ON 013105
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2009to Dec 2015
- 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
- ≥ 18 years of age
- Documented (cytologically confirmed) relapsed/ refractory Lymphoma or B-cell Acute Lymphocytic Leukemia (Philadelphia chromosome negative)
- ECOG Performance Status score of 0, 1, or 2 (see Attachment 1)
- Expected survival, in the opinion of the Investigator, of at least 3 months, to allow a sufficient observation period for evaluation of ON 013105
- Recovery to at least grade I from adverse effects of prior therapies
- Adequate contraceptive [including prescription oral contraceptives (birth control pills), contraceptive injections, intrauterine device (IUD), double-barrier method (spermicidal jelly or foam with condoms or diaphragm), contraceptive patch, or surgical sterilization] before entry and throughout the study for female patients of reproductive potential
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- Female patient with reproductive potential must have a negative serum beta-HCG pregnancy test at screening
- Willing to adhere to the prohibitions and restrictions specified in this protocol
- Patient (or his/her legally authorized representative) must have signed an informed consent document indicating that he/she understands the purpose of and procedures required for the study and is willing to participate in the study
Who cannot join
- Grade 3 thrombocytopenia (platelets <50,000/µL) or neutropenia (ANC <1000/µL) ) except if documented evidence of bone marrow involvement of lymphoma or leukemia contributing to cytopenias.
- Any active malignancy within the past year except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast
- History of HIV-1 seropositivity
- Uncontrolled intercurrent illness including, but not limited to symptomatic congestive heart failure, unstable angina pectoris or cardiac arrhythmia
- Active infection not adequately responding to appropriate therapy.
- Total bilirubin > 1.5 mg/dL not related to hemolysis or Gilbert's disease, AST/ALT > 1.5 X ULN
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- Serum creatinine > 1.5 mg/dL or calculated creatinine clearance < 60 ml/min.
- Ascites requiring active medical management including paracentesis, or hyponatremia (defined as serum sodium value of <130 Meq/L).
- Women patients who are pregnant or lactating
- Male patients with female sexual partners who are unwilling to follow the strict contraception requirements described in this protocol (see Section 4.4).
- Major surgery without full recovery or major surgery within 3 weeks of ON 013105 treatment start.
- Uncontrolled hypertension (defined as a systolic pressure ³ 180 and/or a diastolic pressure ³ 110)
- New onset seizures (within 3 months prior to the first dose of ON 013105) or poorly controlled seizures
- Any concurrent investigational agent or chemotherapy, radiotherapy or immunotherapy
- Psychiatric illness/social situations that would limit the patient's ability to tolerate and/or comply with study requirements
Trial locations and contacts
1 site in 1 country.
United States1 site
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, 33612
About this study
Official title: Phase 1, Dose Escalation Study To Assess the Safety, Pharmacokinetics and Activity of 2-Hour Continuous Intravenous Dosing of ON 013105 Administered Weekly in Patients With Relapsed/Refractory Lymphoma and Acute Lymphoid Leukemia
This is an open-label, dose-escalation Phase 1 study of the investigational agent, ON 013105. In laboratory animal studies, ON 013105 has demonstrated anti-cancer activity. The purpose of this study is to determine the highest dose of ON 013105 that can be given safely in patients with relapsed/refractory Lymphoma or B-cell Acute Lymphocytic Leukemia (Philadelphia chromosome negative). Patients will receive weekly 2-hour IV infusions of ON 013105 at higher and higher doses until intolerable side effects are observed. It is important to know the highest safe dose so additional studies can be done.
Read the detailed description
This is an open-label, dose-escalation Phase I study of ON 013105 in patients with relapsed/refractory Lymphoma or B-cell Acute Lymphocytic Leukemia (Philadelphia chromosome negative) who have satisfied all inclusion/exclusion criteria. Patients will receive weekly 2-hour IV infusions of ON 013105, until evidence of disease progression, intolerable adverse events, or withdrawal of patient consent. Up to 12 additional patients will be treated at the RPTD level. The starting dose will be 17 mg over a 2-hour weekly infusion. Each cycle will comprise three weeks.
Up to 43 patients may be enrolled, of which approximately 7 to 37 patients will be enrolled in the dose escalation portion of the study to determine the RPTD. After the maximally administered dose is attained and at least six patients have received a tentative RPTD, up to 6 additional patients may be enrolled in the dose confirmation phase to confirm the RPTD level.
Treatment will be administered in the Clinical Research center for the first dose for all patients at each given dose level. If there is no toxicity, then subsequent doses at that level for that patient may be administered on an outpatient basis, unless hospitalization is required for another reason.
According to the Simon accelerated titration design, one-patient cohorts and 100% dose increments will be implemented until non-hematological grade 2 toxicity is observed during the first 3-week cycle. The design will then convert to standard 3/6 patient cohorts starting at the dose level where grade 2 toxicity was observed and following 40% dose increments for the subsequent cohorts.
If none of the first three patients experiences a dose-limiting toxicity (DLT) during the first cycle (3 weeks), the next 3 patients will receive the next dose level. If there is a DLT in one of the first three patients, this dose level will be expanded to 6 patients. If 1 patient out of 6 experiences DLT, the next patients will receive the next dose level. If ≥ 2 patients experience DLT at any dose level, this dose level will be declared the Maximally Administered Dose. The Maximally Tolerated Dose (MTD) and RPTD will be the highest dose level below the Maximally Administered Dose with 0 out of 3 patients or one out of 6 patients with DLT. Dosing will be reduced to the immediate lower dose for any patient who experiences a DLT at any time.
If Grade 1 non-hematological toxicity occurs, treatment will be continued at the original dose without dose reduction.
Patients with stable disease or response can continue treatment up to eight 3-week cycles. Further continuation will be determined by the clinical judgment of the Investigator. Patients who drop out for any reason may not re-enter the trial.
Blood samples will be collected during Day 1 of the first cycle for pharmacokinetic assessment. Responses will be assessed according to Cheson, B.D., et al., Revised Response Criteria for Malignant Lymphoma, J Clin Oncol 2007. 25: p. 579-86.
- Conditions
- Lymphoma, Acute Lymphocytic Leukemia
- Being tested
- ON 013105
- Keywords
- Lymphoma, B-cell Acute Lymphocytic Leukemia, ALL
- Medical subject headings
- Lymphoma, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Burkitt Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ON 013105Drug
Also called briciclib
2-hour intravenous infusion once a week. Starting dose is 17 mg. Maximum dose will be 1525 mg.
| Study group | Role | What they receive |
|---|---|---|
| ON 013105 | Experimental | ON 013105 administered intravenously as 2-hour infusion once a week for 3 weeks of 3-week cycles. This is dose escalation study; starting dose is 17 mg. Receives: Drug: ON 013105 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety based on adverse events, hematology and chemical laboratory values, urinalysis, coagulation, ECG, vital signs, physical examination.
Measured: 2 years
Secondary outcomes (2)
Tumor response (according to Cheson, B.D., et al., Revised Response Criteria for Malignant Lymphoma, J Clin Oncol 2007. 25: p. 579-86).
Measured: 2 years
Non-compartmental pharmacokinetic analysis of drug concentrations in plasma including area under concentration time curve, half-life, clearance.
Measured: Day 1 of first cycle
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2010 (estimated)
- Study startNov 2009
- Primary completionDec 2014
- Study completionDec 2015
Why it stopped: Lack of available clinical drug supply
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 LymphomaStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Traws Pharma, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jennifer Cultrera, MD, Principal investigator, H. Lee Moffitt Cancer Center and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01049113
- Sponsor's protocol ID
- ON-013105-01
- Status last verified
- Dec 2015
- First submitted
- 11 Jan 2010
- Last updated
- 8 Dec 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Park IW, Reddy MV, Reddy EP, Groopman JE. Evaluation of novel cell cycle inhibitors in mantle cell lymphoma. Oncogene. 2007 Aug 16;26(38):5635-42. doi: 10.1038/sj.onc.1210350. Epub 2007 Mar 19.
PubMed 17369860Prasad A, Park IW, Allen H, Zhang X, Reddy MV, Boominathan R, Reddy EP, Groopman JE. Styryl sulfonyl compounds inhibit translation of cyclin D1 in mantle cell lymphoma cells. Oncogene. 2009 Mar 26;28(12):1518-28. doi: 10.1038/onc.2008.502. Epub 2009 Feb 9.
PubMed 19198627
Study at a glance
From the registry record, last updated by the sponsor on 8 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1, Dose Escalation Study To Assess the Safety, Pharmacokinetics and Activity of 2-Hour Continuous Intravenous Dosing of ON 013105 Administered Weekly in Patients With Relapsed/Refractory Lymphoma and Acute Lymphoid Leukemia
- ClinicalTrials.gov ID
- NCT01049113
- Acronym / sponsor ID
- ON-013105-01
- Conditions
- Lymphoma, Acute Lymphocytic Leukemia
- Keywords
- Lymphoma, B-cell Acute Lymphocytic Leukemia, ALL
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of available clinical drug supply
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Traws Pharma, Inc.Industry (pharma, biotech, devices)
- Study start
- Nov 2009
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 14 Jan 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.
This is an open-label, dose-escalation Phase 1 study of the investigational agent, ON 013105. In laboratory animal studies, ON 013105 has demonstrated anti-cancer activity. The purpose of this study is to determine the highest dose of ON 013105 that can be given safely in patients with relapsed/refractory Lymphoma or B-cell Acute Lymphocytic Leukemia (Philadelphia chromosome negative). Patients will receive weekly 2-hour IV infusions of ON 013105 at higher and higher doses until intolerable side effects are observed. It is important to know the highest safe dose so additional studies can be done.
Detailed description
This is an open-label, dose-escalation Phase I study of ON 013105 in patients with relapsed/refractory Lymphoma or B-cell Acute Lymphocytic Leukemia (Philadelphia chromosome negative) who have satisfied all inclusion/exclusion criteria. Patients will receive weekly 2-hour IV infusions of ON 013105, until evidence of disease progression, intolerable adverse events, or withdrawal of patient consent. Up to 12 additional patients will be treated at the RPTD level. The starting dose will be 17 mg over a 2-hour weekly infusion. Each cycle will comprise three weeks.
Up to 43 patients may be enrolled, of which approximately 7 to 37 patients will be enrolled in the dose escalation portion of the study to determine the RPTD. After the maximally administered dose is attained and at least six patients have received a tentative RPTD, up to 6 additional patients may be enrolled in the dose confirmation phase to confirm the RPTD level.
Treatment will be administered in the Clinical Research center for the first dose for all patients at each given dose level. If there is no toxicity, then subsequent doses at that level for that patient may be administered on an outpatient basis, unless hospitalization is required for another reason.
According to the Simon accelerated titration design, one-patient cohorts and 100% dose increments will be implemented until non-hematological grade 2 toxicity is observed during the first 3-week cycle. The design will then convert to standard 3/6 patient cohorts starting at the dose level where grade 2 toxicity was observed and following 40% dose increments for the subsequent cohorts.
If none of the first three patients experiences a dose-limiting toxicity (DLT) during the first cycle (3 weeks), the next 3 patients will receive the next dose level. If there is a DLT in one of the first three patients, this dose level will be expanded to 6 patients. If 1 patient out of 6 experiences DLT, the next patients will receive the next dose level. If ≥ 2 patients experience DLT at any dose level, this dose level will be declared the Maximally Administered Dose. The Maximally Tolerated Dose (MTD) and RPTD will be the highest dose level below the Maximally Administered Dose with 0 out of 3 patients or one out of 6 patients with DLT. Dosing will be reduced to the immediate lower dose for any patient who experiences a DLT at any time.
If Grade 1 non-hematological toxicity occurs, treatment will be continued at the original dose without dose reduction.
Patients with stable disease or response can continue treatment up to eight 3-week cycles. Further continuation will be determined by the clinical judgment of the Investigator. Patients who drop out for any reason may not re-enter the trial.
Blood samples will be collected during Day 1 of the first cycle for pharmacokinetic assessment. Responses will be assessed according to Cheson, B.D., et al., Revised Response Criteria for Malignant Lymphoma, J Clin Oncol 2007. 25: p. 579-86.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ON 013105 | Experimental | Drug: ON 013105ON 013105 administered intravenously as 2-hour infusion once a week for 3 weeks of 3-week cycles. This is dose escalation study; starting dose is 17 mg. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- ≥ 18 years of age
- Documented (cytologically confirmed) relapsed/ refractory Lymphoma or B-cell Acute Lymphocytic Leukemia (Philadelphia chromosome negative)
- ECOG Performance Status score of 0, 1, or 2 (see Attachment 1)
- Expected survival, in the opinion of the Investigator, of at least 3 months, to allow a sufficient observation period for evaluation of ON 013105
- Recovery to at least grade I from adverse effects of prior therapies
Key exclusion criteria (15 listed)
- Grade 3 thrombocytopenia (platelets <50,000/µL) or neutropenia (ANC <1000/µL) ) except if documented evidence of bone marrow involvement of lymphoma or leukemia contributing to cytopenias.
- Any active malignancy within the past year except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast
- History of HIV-1 seropositivity
- Uncontrolled intercurrent illness including, but not limited to symptomatic congestive heart failure, unstable angina pectoris or cardiac arrhythmia
- Active infection not adequately responding to appropriate therapy.
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 |
|---|---|---|
| ON 013105Also: briciclib2-hour intravenous infusion once a week. Starting dose is 17 mg. Maximum dose will be 1525 mg. | Drug | ON 013105 |
Primary outcome
Safety based on adverse events, hematology and chemical laboratory values, urinalysis, coagulation, ECG, vital signs, physical examination.
Time frame: 2 years
2 secondary outcomes
Tumor response (according to Cheson, B.D., et al., Revised Response Criteria for Malignant Lymphoma, J Clin Oncol 2007. 25: p. 579-86).
Time frame: 2 years
Non-compartmental pharmacokinetic analysis of drug concentrations in plasma including area under concentration time curve, half-life, clearance.
Time frame: Day 1 of first cycle
Results and safety
The study was stopped early (reason given: Lack of available clinical drug supply). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Dec 2015.
- Background: PubMed 17369860Park IW, Reddy MV, Reddy EP, Groopman JE. Evaluation of novel cell cycle inhibitors in mantle cell lymphoma. Oncogene. 2007 Aug 16;26(38):5635-42. doi: 10.1038/sj.onc.1210350. Epub 2007 Mar 19.
- Background: PubMed 19198627Prasad A, Park IW, Allen H, Zhang X, Reddy MV, Boominathan R, Reddy EP, Groopman JE. Styryl sulfonyl compounds inhibit translation of cyclin D1 in mantle cell lymphoma cells. Oncogene. 2009 Mar 26;28(12):1518-28. doi: 10.1038/onc.2008.502. Epub 2009 Feb 9.
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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.
Jennifer Cultrera, MD principal investigator
H. Lee Moffitt Cancer Center and Research Institute
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 ON 013105 in people with Lymphoma and Acute Lymphocytic Leukemia, run by Traws Pharma, Inc. 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 9 inclusion and 15 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 8 Dec 2015. 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 (reason given: Lack of available clinical drug supply). 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?
Safety based on adverse events, hematology and chemical laboratory values, urinalysis, coagulation, ECG, vital signs, physical examination. (time frame: 2 years). 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 NCT01049113, 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 8 Dec 2015.