LymphomaPhase 1NCT02800889
Dose-Escalation Study of Pixantrone Monotherapy in Pediatric Patients With Relapsed or Refractory Cancer
A Phase 1 study testing Pixantrone in people with Lymphoma and Solid Tumor (Excluding CNS), run by CTI BioPharma at 1 site in United States.
Trial summary
This is a phase 1, open-label, dose escalation study to evaluate the safety, pharmacokinetics, and antitumor activity of pixantrone in pediatric patients with relapsed or refractory solid tumors (excluding those with CNS tumors) or lymphoma. Read more about this study
- Who is it for?
- Ages 6 months to 21 years
- Conditions the study is for
- Lymphoma, Solid Tumor (Excluding CNS)
- What is being tested?
- Pixantrone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Oct 2016to 10 Jul 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 6 months to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patient and/or guardian have signed an Informed Consent Form and Assent approved by the Institutional Review Board or Institutional Ethics Committee, as appropriate and necessary, on a per-age basis
- Age 6 months to 21 years old (initial qualifying diagnosis must have been made at or before the age of 18 and the patient must be under the care of a pediatric hematologist/oncologist)
- Patient received a diagnosis of lymphoma or any non-hematologic malignancy (except central nervous system [CNS] tumors) for which the patient is considered relapsed or refractory. (NOTE: CNS metastases are allowable in patients who are deemed not at risk for progression during the first 30 days, who are neurologically stable, and, if on corticosteroids, have been on a stable corticosteroid dose for at least 2 weeks.) Patients who have >1 malignancy ongoing during screening are not eligible
- Patient must have one or more of the following treatment statuses:
- Has failed at least 2 prior lines of chemotherapy
- Has no curative chemotherapy treatment option available
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- Is not considered a candidate for available chemotherapy treatment options
- In dose-escalation accrual, patients may have un-measurable disease (such as bone marrow/bone involvement or diffuse tumors)
- In dose-escalation accrual, patients may have un-measurable disease in cases where the standard of care would indicate the need for adjuvant chemotherapy after definitive surgery or radiation, but for whom no standard chemotherapy options are available
- In expansion cohort accrual, patients must have disease that is evaluable or measurable for response and progression per standard criteria for their diagnosis (Refer to the Appendices: RECIST 1.1 Criteria for Evaluation of Solid Tumors, Including Neuroblastoma, Appendix 18.4], Evaluation of Neuroblastoma [Appendix 18.6], and the Lymphoma Staging and Disease Response Criteria [Appendix 18.5])
- Karnofsky-Lansky performance status (as per age of patient) ≥50 (Appendix 18.1)
- Patient must have one or more of the following cardiac function measurements by echocardiogram:
- Left ventricular ejection fraction (LVEF) ≥55%
- Left ventricular shortening fraction (LVSF) ≥27%
- Hemoglobin ≥8 g/dL (can be post-transfusion)
- Platelet count ≥75 × 109/L
- Absolute neutrophil count (ANC) ≥0.75 × 109/L
- Serum direct/conjugated bilirubin ≤1.5 × upper limit of normal (ULN); patients with clinically diagnosed Gilbert's syndrome and total bilirubin ≤5 × ULN may be enrolled
- Aspartate aminotransferase (AST; also called serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT; also called serum glutamic-pyruvic transaminase [SGPT]) ≤2.5 × ULN, or ≤5 × ULN if elevation is due to hepatic involvement by tumor
- Serum creatinine ≤2 × ULN
- Patients must meet the following criteria with respect to prior cancer therapy, radiotherapy, and stem cell transplants:
- Myelosuppressive chemotherapy: At least 3 weeks must have elapsed since the completion of myelosuppressive chemotherapy (4 weeks if prior nitrosourea) and resolution of all nonhematologic toxicities to ≤grade 1.
- Biologic (anti-neoplastic agent):
- Oral tyrosine kinase inhibitors or other similar agents. At least 7 days must have elapsed since the completion of therapy with a biologic agent and all non-hematologic toxicities must have resolved to ≤grade 1 prior to enrollment
- Anti-IGFR-1R and other monoclonal antibodies: the shorter of 3 half-lives or 6 weeks must have elapsed since previous monoclonal antibody therapy and resolution of all non-hematologic toxicities to ≤grade 1 prior to enrollment
- Myeloid Growth Factor: Must not have received within 1 week prior to entry into this study (2 weeks in the case of PEG-filgrastim)
- Radiotherapy: At least 4 weeks must have elapsed and all non-hematologic toxicities must have resolved to ≤grade 1 prior to enrollment. Previously radiated lesions cannot be used to assess response unless those sites are the sites of disease progression
- Stem cell transplant (SCT): For autologous SCT, ≥3 months must have elapsed. For allogeneic SCT, ≥6 months must have elapsed and there must be no evidence of active graft versus host disease
- All acute toxicities related to prior treatment recovered to grade ≤1 , except alopecia and hematologic parameters specified in the inclusion criteria
- Willingness and ability to comply with the visit schedule and assessments required by the study protocol, including effective birth control (Section 5.4) for sexually active patients
Who cannot join
- Investigator-predicted life expectancy of less than two months
- Investigator-predicted inability to tolerate pixantrone monotherapy treatment adverse effects for less than two months
- Prior anthracycline treatment with a cumulative dose exceeding 450 mg/m2 (calculated based on doxorubicin equivalents)
- Active National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) ≥grade 3 infection, or a lower grade infection deemed resistant or refractory to available antimicrobial agents, or infection requiring ongoing antibiotic treatment
- Major surgery ≤7 days and/or with incomplete/inadequate wound healing prior to start of study treatment
- Known acute or chronic hepatitis B or hepatitis C virus infection
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- Known seropositivity for human immunodeficiency virus (HIV)
- Any experimental/investigational therapy ≤28 days prior to start of study treatment
- Myocardial infarction within the past 6 months
- New York Heart Association class II, III or IV heart failure
- Any contraindication, known allergy, or hypersensitivity to any investigational drug(s)
- Pregnant or lactating
- Planned radiotherapy or surgical procedures for the qualifying malignancy
- Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study procedures or follow-up schedules
- Other severe and/or uncontrolled medical disease that could compromise participation in the study, or any medical or psychiatric condition that, in the opinion of the investigator, would make study drug administration hazardous or obscure the interpretation of data
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital Los Angeles
Los Angeles, California, 90027
About this study
Official title: A Phase 1, Dose-Escalation Study of Pixantrone Monotherapy in Pediatric Patients With Relapsed or Refractory Cancer
This is a phase 1, open-label, dose escalation study to evaluate the safety, pharmacokinetics, and antitumor activity of pixantrone in pediatric patients with relapsed or refractory solid tumors (excluding those with CNS tumors) or lymphoma.
Read the detailed description
Approximately thirty-five eligible patients will receive up to six 28-day cycles of pixantrone monotherapy, with two additional cycles in patients who continue to benefit from treatment. Each patient will receive pixantrone administered intravenously on days 1, 8, and 15 of each 28-day cycle. There will be three age cohorts, defined as age cohort 1 (12 to less than 18 years, plus young adults (ages 18-21 years)), age cohort 2 (5 to less than 12 years), and age cohort 3 (6 months to less than 5 years). During dose escalation, three patients will first be accrued to the starting dose level. If no DLTs are identified, that dose level will be declared to not exceed the MTD and three patients will be accrued to the next higher dose level. Each subsequent dose-escalation level will be accrued per the DLT/MTD determination schema above. Planned sequential dose-escalation phase will receive 40 mg/m2, 50 mg/m2, 60 mg/m2 or 70 mg/m2 of pixantrone base (on days 1, 8 and 15), as tolerated, based on DLT evaluation.Dose escalations will follow a standard 3+3 patient cohort escalation plan. No patients from Age Cohort 3 will be enrolled until 6 patients from age cohorts 1 and 2 (combined) are evaluable for toxicity. After the MTD has been determined, an expansion phase will be accrued in order to gain better estimates of the safety, tolerability, and anti-tumor activity of pixantrone monotherapy in pediatric patients when treated at the MTD. Patients will be offered 3 years of post-study extension phase follow-up with periodic assessments of cardiac function parameters.
- Conditions
- Lymphoma, Solid Tumor (Excluding CNS)
- Being tested
- Pixantrone
- Keywords
- relapsed, refractory, solid tumors
- Medical subject headings
- Lymphoma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PixantroneDrug
Also called Pixantrone (BBR 2778)
Pixantrone
| Study group | Role | What they receive |
|---|---|---|
| Treatment: Pixantrone | Experimental | Each patient will receive pixantrone monotherapy administered intravenously once on days 1, 8, and 15 up to six 28-day cycles of pixantrone monotherapy, with two additional cycles in patients who continue to benefit from treatment. At least 6 patients each from Age Cohorts 1 and 2 will be accrued into dose escalation cohorts. The study will be opened to patients of Age Cohort 3 only after at least 6 patients in Age Cohorts 1 and 2 (combined) have been evaluated for toxicity. During the dose escalation phase, participants who are inevaluable for DLT for reasons unequivocally unrelated to toxicity will be replaced. Expansion cohort accrual quota-At least 15 evaluable patients treated with the MTD/optimal dose will be accrued in total, of which 7 patients will be in Age Cohort 2. Receives: Drug: Pixantrone |
What is being measured
The primary outcome is the main question the study is designed to answer.
MTD, defined as the highest dose level at which no more than 1/6 patients experience DLT
Dose Escalation- The study will follow a standard 3+3 patient cohort escalation design, evaluating up to 4 dose levels.
Measured: 28 days
Anti-tumor activity of pixantrone at the MTD
Dose Expansion Cohort- Anti-tumor activity will be summarized by disease type, dose level, and age cohort for all patients in the evaluable population. The best overall response rate, defined as the proportion of patients that achieved a complete or partial response, will be summarized by disease type and a 95% confidence interval will be provided. A similar summary will be provided for the complete response rate.
Measured: approx. 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2016 (estimated)
- Study start24 Oct 2016
- Primary completion10 Jul 2018
- Study completion10 Jul 2018
Why it stopped: Study withdrawn; no participants enrolled
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- CTI BioPharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Leo Mascarenhas, MD. MS., Principal investigator, CHLA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02800889
- Sponsor's protocol ID
- PIX111
- Status last verified
- Jan 2020
- First submitted
- 3 Jun 2016
- Last updated
- 29 Jan 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 29 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Dose-Escalation Study of Pixantrone Monotherapy in Pediatric Patients With Relapsed or Refractory Cancer
- ClinicalTrials.gov ID
- NCT02800889
- Acronym / sponsor ID
- PIX111
- Conditions
- Lymphoma, Solid Tumor (Excluding CNS)
- Keywords
- relapsed, refractory, solid tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study withdrawn; no participants enrolled
- Enrolment
- 0 participants (actual)
- Lead sponsor
- CTI BioPharmaIndustry (pharma, biotech, devices)
- Study start
- 24 Oct 2016 (actual)
- Primary completion
- 10 Jul 2018 (actual)
- Study completion
- 10 Jul 2018 (actual)
- First posted
- 15 Jun 2016 (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 a phase 1, open-label, dose escalation study to evaluate the safety, pharmacokinetics, and antitumor activity of pixantrone in pediatric patients with relapsed or refractory solid tumors (excluding those with CNS tumors) or lymphoma.
Detailed description
Approximately thirty-five eligible patients will receive up to six 28-day cycles of pixantrone monotherapy, with two additional cycles in patients who continue to benefit from treatment. Each patient will receive pixantrone administered intravenously on days 1, 8, and 15 of each 28-day cycle. There will be three age cohorts, defined as age cohort 1 (12 to less than 18 years, plus young adults (ages 18-21 years)), age cohort 2 (5 to less than 12 years), and age cohort 3 (6 months to less than 5 years). During dose escalation, three patients will first be accrued to the starting dose level. If no DLTs are identified, that dose level will be declared to not exceed the MTD and three patients will be accrued to the next higher dose level. Each subsequent dose-escalation level will be accrued per the DLT/MTD determination schema above. Planned sequential dose-escalation phase will receive 40 mg/m2, 50 mg/m2, 60 mg/m2 or 70 mg/m2 of pixantrone base (on days 1, 8 and 15), as tolerated, based on DLT evaluation.Dose escalations will follow a standard 3+3 patient cohort escalation plan. No patients from Age Cohort 3 will be enrolled until 6 patients from age cohorts 1 and 2 (combined) are evaluable for toxicity. After the MTD has been determined, an expansion phase will be accrued in order to gain better estimates of the safety, tolerability, and anti-tumor activity of pixantrone monotherapy in pediatric patients when treated at the MTD. Patients will be offered 3 years of post-study extension phase follow-up with periodic assessments of cardiac function parameters.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment: Pixantrone | Experimental | Drug: PixantroneEach patient will receive pixantrone monotherapy administered intravenously once on days 1, 8, and 15 up to six 28-day cycles of pixantrone monotherapy, with two additional cycles in patients who continue to benefit from treatment. At least 6 patients each from Age Cohorts 1 and 2 will be accrued into dose escalation cohorts. The study will be opened to patients of Age Cohort 3 only after at least 6 patients in Age Cohorts 1 and 2 (combined) have been evaluated for toxicity. During the dose escalation phase, participants who are inevaluable for DLT for reasons unequivocally unrelated to toxicity will be replaced. Expansion cohort accrual quota-At least 15 evaluable patients treated with the MTD/optimal dose will be accrued in total, of which 7 patients will be in Age Cohort 2. |
Who may qualify
- Ages
- 6 months to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (30 listed)
- Patient and/or guardian have signed an Informed Consent Form and Assent approved by the Institutional Review Board or Institutional Ethics Committee, as appropriate and necessary, on a per-age basis
- Age 6 months to 21 years old (initial qualifying diagnosis must have been made at or before the age of 18 and the patient must be under the care of a pediatric hematologist/oncologist)
- Patient received a diagnosis of lymphoma or any non-hematologic malignancy (except central nervous system [CNS] tumors) for which the patient is considered relapsed or refractory. (NOTE: CNS metastases are allowable in patients who are deemed not at risk for progression during the first 30 days, who are neurologically stable, and, if on corticosteroids, have been on a stable corticosteroid dose for at least 2 weeks.) Patients who have >1 malignancy ongoing during screening are not eligible
- Patient must have one or more of the following treatment statuses:
- In dose-escalation accrual, patients may have un-measurable disease (such as bone marrow/bone involvement or diffuse tumors)
Key exclusion criteria (15 listed)
- Investigator-predicted life expectancy of less than two months
- Investigator-predicted inability to tolerate pixantrone monotherapy treatment adverse effects for less than two months
- Prior anthracycline treatment with a cumulative dose exceeding 450 mg/m2 (calculated based on doxorubicin equivalents)
- Active National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) ≥grade 3 infection, or a lower grade infection deemed resistant or refractory to available antimicrobial agents, or infection requiring ongoing antibiotic treatment
- Major surgery ≤7 days and/or with incomplete/inadequate wound healing prior to start of study treatment
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 |
|---|---|---|
| PixantroneAlso: Pixantrone (BBR 2778)Pixantrone | Drug | Treatment: Pixantrone |
Primary outcome
MTD, defined as the highest dose level at which no more than 1/6 patients experience DLT
Time frame: 28 days
Dose Escalation- The study will follow a standard 3+3 patient cohort escalation design, evaluating up to 4 dose levels.
Anti-tumor activity of pixantrone at the MTD
Time frame: approx. 1 year
Dose Expansion Cohort- Anti-tumor activity will be summarized by disease type, dose level, and age cohort for all patients in the evaluable population. The best overall response rate, defined as the proportion of patients that achieved a complete or partial response, will be summarized by disease type and a 95% confidence interval will be provided. A similar summary will be provided for the complete response rate.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2020.
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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.
Leo Mascarenhas, MD. MS. principal investigator
CHLA
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 Pixantrone in people with Lymphoma and Solid Tumor (Excluding CNS), run by CTI BioPharma 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 30 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: withdrawn, as of the sponsor's last update on 29 Jan 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 was withdrawn before enrolling participants, so there are no results.
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?
MTD, defined as the highest dose level at which no more than 1/6 patients experience DLT (time frame: 28 days). The study lists 2 primary outcomes in all. 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 29 Jan 2020.