Hematological MalignanciesPhase 1NCT02931110
Study of IV CBL0137 in Previously Treated Hematological Subjects
A Phase 1 study testing CBL0137 in people with Hematological Malignancies, run by Incuron at 4 sites in United States.
Trial summary
This clinical trial is a Phase 1, open-label, sequential-group, dose-escalation (Part 1) and cohort-expansion study (Part 2) evaluating the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of intravenously (IV) administered CBL0137 in participants with previously treated hematological malignancies. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hematological Malignancies
- What is being tested?
- CBL0137
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 4 sitesUnited States
- Study dates
- Jan 2017to Oct 2020
- 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
- Presence of an active hematological malignancy:
- Part 1 (Dose Escalation): Diagnosis of B-cell DLBCL, FL, MCL, HL, CLL/SLL, or MM as documented by medical records.
- Part 2 (Cohort Expansion): Diagnosis of DLBCL, FL, MCL, HL, CLL/SLL, ALL, MM, or AML as documented in medical records.
- Requirement for therapy of the hematological malignancy due to disease-related symptoms, lymphadenopathy, organomegaly, extranodal organ involvement, or progressive disease.
- Hematological malignancy has been previously treated, has relapsed after or progressed during prior therapy, and has limited potential for benefit from currently available therapy, including hematopoietic stem cell transplantation.
- Presence of measurable disease:
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- For subjects with DLBCL, FL, MCL, HL, or CLL/SLL: presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (defined as the presence of ≥1 lesion that measures ≥2.0 cm in the longest dimension and ≥1.0 cm in the longest perpendicular dimension as assessed by computed tomography).
- For subjects with MM, measurable disease with serum monoclonal immunoglobulin protein (M-protein) ≥1 g/dL, or urine M-protein protein ≥200 mg/24 hours, or involved serum free light chain ≥10 mg/dL.
- For subjects with ALL or AML, presence of >5% blasts in the bone marrow (based on a bone marrow aspirate/biopsy sample with ≥200 nucleated cells and the presence of bone marrow spicules) and/or >1 x 109/L blasts in the peripheral blood (with the restriction that peripheral blast count in subjects with AML must be <50 x 109/L prior to the start of study therapy).
- Completion of all previous therapy (including surgery, radiotherapy, chemotherapy, immunotherapy, or investigational therapy) for the treatment of cancer ≥2 weeks before the start of study therapy. Note: For subjects with AML, the use of hydroxyurea for management of leukocytosis is allowed in Cycle 1 if hydroxyurea is started prior to the initiation of study therapy.
Who cannot join
- Part 2 (Cohort Expansion): History of another malignancy except for the following: adequately treated local basal cell or squamous cell carcinoma of the skin; adequately treated carcinoma in situ without evidence of disease; adequately treated, papillary, noninvasive bladder cancer; other adequately treated Stage 1 or 2 cancers currently in complete remission; or any other cancer that has been in complete remission for ≥2 years.
- Rapidly progressive, clinically unstable central nervous system hematological malignancy. Note: Central nervous system evaluation is only required in subjects with known or suspected central nervous system malignancy.
- Significant cardiovascular disease, including myocardial infarction, arterial thromboembolism, or cerebrovascular thromboembolism, within 6 months prior to start of study therapy; symptomatic dysrhythmias or unstable dysrhythmias requiring medical therapy; angina requiring therapy; symptomatic peripheral vascular disease; New York Heart Association Class 3 or 4 congestive heart failure; uncontrolled Grade ≥3 hypertension (diastolic blood pressure ≥100 mmHg or systolic blood pressure ≥160 mmHg) despite antihypertensive therapy; or history of congenital prolonged QT syndrome.
- Significant screening ECG abnormalities, including unstable cardiac arrhythmia requiring medication, atrial fibrillation/flutter, left bundle-branch block, 2nd-degree atrioventricular (AV) block type II, 3rd degree AV block, Grade ≥2 bradycardia, or QT corrected for heart rate (QTc) >450 msec (for men) or >470 msec (for women).
- Ongoing risk for bleeding due to active gastrointestinal disease or bleeding diathesis.
- Evidence of an ongoing systemic bacterial, fungal, or viral infection (including upper respiratory tract infections) at the time of start of study therapy. Note: Subjects with localized fungal infections of skin or nails are eligible.
- In subjects with prior progenitor cell transplantation, evidence of ongoing graft-versus-host disease.
- Please speak with Investigator for the complete Inclusion/Exclusion criteria.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Claude Sportes
Augusta, Georgia, 30912
Roswell Park Cancer Institute
Buffalo, New York, 14263
University Hospitals Case Medical
Cleveland, Ohio, 44106
The Oncology Institute of Hope & Innovation
Whittier, California, 90603
About this study
Official title: A Phase 1 Dose-Escalation and Cohort-Expansion Study of Intravenous CBL0137 in Subjects With Previously Treated Hematological Cancers
This clinical trial is a Phase 1, open-label, sequential-group, dose-escalation (Part 1) and cohort-expansion study (Part 2) evaluating the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of intravenously (IV) administered CBL0137 in participants with previously treated hematological malignancies.
Read the detailed description
Part 1 of the study will evaluate the safety and pharmacology of a range of CBL0137 doses administered IV in participants with previously treated lymphomas, including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), Hodgkin lymphoma (HL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), or multiple myeloma (MM). Cohorts of 3 to 6 subjects will be sequentially enrolled at progressively higher dose levels of CBL0137 using a standard 3+3 dose-escalation design. An additional 6 participants may be accrued at the maximum tolerated dose (MTD) or at the recommended dose (RD) to confirm CBL0137 safety and pharmacology as a prelude to further clinical evaluation.
Part 2 of the study provides cohort expansion to further explore the safety, pharmacology, and clinical activity of CBL0137 monotherapy in participants with specific previously treated hematological cancers, including DLBCL, FL, MCL, HL, CLL/SLL, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and MM. Twelve evaluable participants with each disease type may be enrolled.
- Conditions
- Hematological Malignancies
- Being tested
- CBL0137
- Keywords
- Diffuse large B-cell lymphoma (DLBCL), Follicular lymphoma (FL), Mantle cell lymphoma (MCL), Hodgkin lymphoma (HL), Chronic lymphocytic leukemia/small lymphocytic lymphoma, Multiple myeloma (MM), Acute lymphoblastic leukemia (ALL), Acute myeloid leukemia (AML)
- Medical subject headings
- Hematologic Neoplasms, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Follicular, Lymphoma, Mantle-Cell, Hodgkin Disease, Leukemia, Lymphocytic, Chronic, B-Cell, Multiple Myeloma, Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CBL0137Drug
Also called Curaxin
CBL0137 administered IV weekly on Days 1 and 8 of repeated 21 day treatment cycles. Number of Cycles: 2 or until progression or unacceptable toxicity develops
| Study group | Role | What they receive |
|---|---|---|
| CBL0137 Dose Escalation | Experimental | * Dose Level 1: 150mg/m2, IV
* Dose Level 2: 180mg/m2, IV
* Dose Level 3: 240mg/m2, IV
* Dose Level 4: 320mg/m2, IV
* Dose Level 5: 400mg/m2, IV
* Dose Level 6: 540mg/m2, IV
* Dose Level 7: 650mg/m2, IV
* Dose Level 8: 780mg/m2, IV
* Dose Level 9: 950mg/m2, IV
* Dose Level 10: 1150mg/m2, IV
* Dose Level 11: 1400mg/m2, IV
* Dose Level 12: 1700mg/m2, IV
* Dose Level 13: 2000mg/m2, IV
* Dose Level 14: 2400mg/m2, IV
* Dose Level 15: 2900mg/m2, IV
* Dose Level 16: 3500mg/m2, IV Receives: Drug: CBL0137 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1: Maximum Tolerated Dose (MTD) and Recommended Dose (RD)
MTD is defined as dose level at which ≥6 subjects have been treated and which is associated with a first-cycle dose-limiting toxicity (DLT) in ≤17% of the participants. RD may be the MTD or may be a lower dose within the tolerable dose range. Selection of the RD will be based on consideration of short- and long-term safety information together with available pharmacokinetic, pharmacodynamic, and efficacy data.
Measured: At the end of Cycle 1 (each cycle is 21 days)
Part 2: Overall Response Rate (ORR)
ORR is defined as the proportion of subjects who achieve a complete response (CR), complete response with incomplete blood count recovery (CRi), or partial response (PR) for those with DLBCL, FL, MCL, HL, or CLL/SLL; the proportion of subjects who achieve a CR, CRi, or unconfirmed CR (CRu) for those with ALL; the portion of subjects who achieve a CR or CRi for those with AML; and the proportion of subjects who achieve a stringent CR (sCR), CR, very good PR (VGPR), or PR for those with MM. An ORR of ≥20% is considered the minimum value of potential interest in each of the selected indications.
Measured: Through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2016 (estimated)
- Study startJan 2017
- Primary completionOct 2020
- Study completionOct 2020
Why it stopped: Business reasons
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hematological MalignanciesStudies 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
- Sequential
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Incuron
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Langdon Miller, MD, Study director, CBLI on behalf of Incuron, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02931110
- Sponsor's protocol ID
- I137-102
- Status last verified
- Dec 2020
- First submitted
- 6 Jun 2016
- Last updated
- 10 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Dose-Escalation and Cohort-Expansion Study of Intravenous CBL0137 in Subjects With Previously Treated Hematological Cancers
- ClinicalTrials.gov ID
- NCT02931110
- Acronym / sponsor ID
- I137-102
- Conditions
- Hematological Malignancies
- Keywords
- Diffuse large B-cell lymphoma (DLBCL), Follicular lymphoma (FL), Mantle cell lymphoma (MCL), Hodgkin lymphoma (HL), Chronic lymphocytic leukemia/small lymphocytic lymphoma, Multiple myeloma (MM), Acute lymphoblastic leukemia (ALL), Acute myeloid leukemia (AML)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Business reasons
- Enrolment
- 5 participants (actual)
- Lead sponsor
- IncuronIndustry (pharma, biotech, devices)
- Study start
- Jan 2017 (actual)
- Primary completion
- Oct 2020 (actual)
- Study completion
- Oct 2020 (actual)
- First posted
- 12 Oct 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 clinical trial is a Phase 1, open-label, sequential-group, dose-escalation (Part 1) and cohort-expansion study (Part 2) evaluating the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of intravenously (IV) administered CBL0137 in participants with previously treated hematological malignancies.
Detailed description
Part 1 of the study will evaluate the safety and pharmacology of a range of CBL0137 doses administered IV in participants with previously treated lymphomas, including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), Hodgkin lymphoma (HL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), or multiple myeloma (MM). Cohorts of 3 to 6 subjects will be sequentially enrolled at progressively higher dose levels of CBL0137 using a standard 3+3 dose-escalation design. An additional 6 participants may be accrued at the maximum tolerated dose (MTD) or at the recommended dose (RD) to confirm CBL0137 safety and pharmacology as a prelude to further clinical evaluation.
Part 2 of the study provides cohort expansion to further explore the safety, pharmacology, and clinical activity of CBL0137 monotherapy in participants with specific previously treated hematological cancers, including DLBCL, FL, MCL, HL, CLL/SLL, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and MM. Twelve evaluable participants with each disease type may be enrolled.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CBL0137 Dose Escalation | Experimental | Drug: CBL0137* Dose Level 1: 150mg/m2, IV * Dose Level 2: 180mg/m2, IV * Dose Level 3: 240mg/m2, IV * Dose Level 4: 320mg/m2, IV * Dose Level 5: 400mg/m2, IV * Dose Level 6: 540mg/m2, IV * Dose Level 7: 650mg/m2, IV * Dose Level 8: 780mg/m2, IV * Dose Level 9: 950mg/m2, IV * Dose Level 10: 1150mg/m2, IV * Dose Level 11: 1400mg/m2, IV * Dose Level 12: 1700mg/m2, IV * Dose Level 13: 2000mg/m2, IV * Dose Level 14: 2400mg/m2, IV * Dose Level 15: 2900mg/m2, IV * Dose Level 16: 3500mg/m2, IV |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Presence of an active hematological malignancy:
- Requirement for therapy of the hematological malignancy due to disease-related symptoms, lymphadenopathy, organomegaly, extranodal organ involvement, or progressive disease.
- Hematological malignancy has been previously treated, has relapsed after or progressed during prior therapy, and has limited potential for benefit from currently available therapy, including hematopoietic stem cell transplantation.
- Presence of measurable disease:
- Completion of all previous therapy (including surgery, radiotherapy, chemotherapy, immunotherapy, or investigational therapy) for the treatment of cancer ≥2 weeks before the start of study therapy. Note: For subjects with AML, the use of hydroxyurea for management of leukocytosis is allowed in Cycle 1 if hydroxyurea is started prior to the initiation of study therapy.
Key exclusion criteria (8 listed)
- Part 2 (Cohort Expansion): History of another malignancy except for the following: adequately treated local basal cell or squamous cell carcinoma of the skin; adequately treated carcinoma in situ without evidence of disease; adequately treated, papillary, noninvasive bladder cancer; other adequately treated Stage 1 or 2 cancers currently in complete remission; or any other cancer that has been in complete remission for ≥2 years.
- Rapidly progressive, clinically unstable central nervous system hematological malignancy. Note: Central nervous system evaluation is only required in subjects with known or suspected central nervous system malignancy.
- Significant cardiovascular disease, including myocardial infarction, arterial thromboembolism, or cerebrovascular thromboembolism, within 6 months prior to start of study therapy; symptomatic dysrhythmias or unstable dysrhythmias requiring medical therapy; angina requiring therapy; symptomatic peripheral vascular disease; New York Heart Association Class 3 or 4 congestive heart failure; uncontrolled Grade ≥3 hypertension (diastolic blood pressure ≥100 mmHg or systolic blood pressure ≥160 mmHg) despite antihypertensive therapy; or history of congenital prolonged QT syndrome.
- Significant screening ECG abnormalities, including unstable cardiac arrhythmia requiring medication, atrial fibrillation/flutter, left bundle-branch block, 2nd-degree atrioventricular (AV) block type II, 3rd degree AV block, Grade ≥2 bradycardia, or QT corrected for heart rate (QTc) >450 msec (for men) or >470 msec (for women).
- Ongoing risk for bleeding due to active gastrointestinal disease or bleeding diathesis.
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 |
|---|---|---|
| CBL0137Also: CuraxinCBL0137 administered IV weekly on Days 1 and 8 of repeated 21 day treatment cycles. Number of Cycles: 2 or until progression or unacceptable toxicity develops | Drug | CBL0137 Dose Escalation |
Primary outcome
Part 1: Maximum Tolerated Dose (MTD) and Recommended Dose (RD)
Time frame: At the end of Cycle 1 (each cycle is 21 days)
MTD is defined as dose level at which ≥6 subjects have been treated and which is associated with a first-cycle dose-limiting toxicity (DLT) in ≤17% of the participants. RD may be the MTD or may be a lower dose within the tolerable dose range. Selection of the RD will be based on consideration of short- and long-term safety information together with available pharmacokinetic, pharmacodynamic, and efficacy data.
Part 2: Overall Response Rate (ORR)
Time frame: Through study completion, an average of 1 year
ORR is defined as the proportion of subjects who achieve a complete response (CR), complete response with incomplete blood count recovery (CRi), or partial response (PR) for those with DLBCL, FL, MCL, HL, or CLL/SLL; the proportion of subjects who achieve a CR, CRi, or unconfirmed CR (CRu) for those with ALL; the portion of subjects who achieve a CR or CRi for those with AML; and the proportion of subjects who achieve a stringent CR (sCR), CR, very good PR (VGPR), or PR for those with MM. An ORR of ≥20% is considered the minimum value of potential interest in each of the selected indications.
Results and safety
The study was stopped early (reason given: Business reasons). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Dec 2020.
- Individual participant dataSharing planned: No
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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.
Langdon Miller, MD study director
CBLI on behalf of Incuron, Inc.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CBL0137 in people with Hematological Malignancies, run by Incuron at 4 sites 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 10 inclusion and 8 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 10 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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: Business reasons). 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?
Part 1: Maximum Tolerated Dose (MTD) and Recommended Dose (RD) (time frame: At the end of Cycle 1 (each cycle is 21 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 10 Dec 2020.