Chronic Myeloproliferative DisordersPhase 1/2NCT00669578

CC-4047 in Treating Patients With Myelofibrosis

A Phase 1/2 study testing CC-4047 in people with Chronic Myeloproliferative Disorders and Secondary Myelofibrosis, run by Mayo Clinic at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

RATIONALE: Biological therapies, such as CC-4047, may stimulate the immune system in different ways and stop cancer cells from growing. CC-4047 may also stop the growth of cancer cells by blocking blood flow to the cancer. Read more about this study

Who is it for?: Ages 18 to 120 years
Conditions the study is for: Chronic Myeloproliferative Disorders, Secondary Myelofibrosis
What is being tested?: CC-4047
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 77 participants
Where: 1 siteUnited States
Study dates: May 2008to 12 Dec 2019
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 120 years
All sexes
No healthy volunteers
Adult, Older adult

DISEASE CHARACTERISTICS:

Diagnosis of primary and post essential thrombocythemia (ET) or post polycythemia vera (PV) myelofibrosis requiring therapy
De novo presentation (i.e., agnogenic myeloid metaplasia AND post ET or post PV myelofibrosis)
Developed after an antecedent history of PV (i.e., post polycythemic myeloid metaplasia) or essential polycythemia (i.e., post thrombocythemic myeloid metaplasia)
Total hemoglobin < 10 g/dL OR transfusion dependent anemia (defined by a history of ≥ 2 units of red blood cell (RBC) transfusions within the past 28 days for hemoglobin < 8.5 g/dL that was not associated with overt bleeding) OR marked splenomegaly (e.g., ≥ 10 cm below costal margin)

PATIENT CHARACTERISTICS:

Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Absolute neutrophil count (ANC) ≥ 500/μL
Platelet count ≥ 20,000/μL
Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 3 times upper limit of normal (ULN) (≤ 5 times ULN if attributed to hepatic extramedullary hematopoiesis)
Total bilirubin ≤ 3 times ULN OR direct bilirubin ≤ 2 times ULN
Serum creatinine ≤ 2.0 mg/dL
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective double-method contraception for ≥ 28 days before, during, and for ≥ 28 days after completion of study treatment
Agrees to abstain from donating blood, semen, or sperm during and for ≥ 28 days after completion of study treatment
Willing to undergo transfusion of blood products (if applicable)
Able to complete questionnaire(s) alone or with assistance
No known HIV positivity, hepatitis B carrier, or active hepatitis C infection
No serious medical condition, psychiatric illness, or any other condition, including the presence of laboratory abnormalities, that (as judged by the treating physician) would preclude giving informed consent or participating in the study or confound the ability to interpret data from the study
No other active malignancies, except basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast
No active deep vein thrombosis or pulmonary embolism that has not been therapeutically anticoagulated

PRIOR CONCURRENT THERAPY:

Recovered from all prior therapy
No prior CC-4047
More than 28 days since prior growth factors, cytotoxic chemotherapeutic agents (e.g., hydroxyurea or anagrelide), corticosteroids, or experimental drugs or therapies
No other concurrent experimental drugs or therapies or cytotoxic chemotherapeutic agents (e.g., hydroxyurea or anagrelide) for myelofibrosis
No concurrent growth factors (including erythropoietin) for myelofibrosis, except G-CSF or pegfilgrastim
No concurrent chronic use (i.e., > 2 weeks) of more than physiologic doses of corticosteroids (dose equivalent to > 10 mg/day of prednisone)

Trial locations and contacts

1 site in 1 country.

United States1 site

Mayo Clinic
Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: A Phase I/II, Prospective, Open-Label Study to Determine the Safety and Efficacy of CC-4047 in Patients With Primary, Post Polycythemia Vera, or Post Essential Thrombocythemia Myelofibrosis®

PURPOSE: This trial is studying the side effects and best dose of CC-4047 and to see how well it works in treating patients with myelofibrosis.

Read the detailed description

OBJECTIVES:

Phase I:

Primary

To determine the Maximum Tolerated Dose of CC-4047 in the treatment of Primary, Post Polycythemia Vera, or Post Essential Thrombocythemia Myelofibrosis (PMF, post-PV MF, or post-ET MF).

Phase II:

Primary

Best overall response as determined by International Working Group Criteria over the first 6 cycles (168 days) of study treatment.

Secondary

Safety (type, frequency, severity [National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0] of adverse events (AEs), and relationship of AEs to CC-4047.
Duration of response.
Time to response.
Best overall response as determined by International Working Group Criteria over the first 12 cycles (336 days) of study treatment.

OUTLINE: Patients receive oral CC-4047. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 28 days and then every 6 months for up to 3 years.

Conditions: Chronic Myeloproliferative Disorders, Secondary Myelofibrosis
Being tested: CC-4047
Keywords: secondary myelofibrosis, polycythemia vera, essential thrombocythemia, primary myelofibrosis
Medical subject headings: Myeloproliferative Disorders, Polycythemia Vera, Thrombocythemia, Essential, Primary Myelofibrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CC-4047Drug
CC-4047: taken orally each day in a 28 day cycle.

Study groups in NCT00669578
Study group	Role	What they receive
CC-4047	Experimental	Not described Receives: Drug: CC-4047

What is being measured

The primary outcome is the main question the study is designed to answer.

Determine the Maximum Tolerated Dose of CC-4047
Starting at a dose level of 2.5 mg/d on days 1-21 in every 28 day cycle, participants were accrued in cohorts of three to assess dose limiting toxicities (DLT) and determine the maximum tolerated dose (MTD). Dose escalation at increments of 0.5 mg/d was done if no subject had a DLT (a grade 4 or higher hematologic toxicity or a grade 3 or higher febrile neutropenia or a grade 3 or higher non-hematologic toxicity) in cycle 1. Subsequent cohorts were treated until the maximum tolerated dose (MTD) was reached (dose level before that which results in a DLT in >1 of 6 subjects). Subsequent participants were treated at the MTD, those without response at the MTD after 3 cycles were lowered to the minimal efficacious dose (MED) of 0.5 mg daily. Here, we are reporting the percentage of participants in Phase I with a DLT at each dose level.
Measured: The first 28-day cycle of treatment.
Best Overall Response Over the First 6 Cycles of Treatment
Response evaluation:
Complete Remission (CR):
Neutrophil count between 1 to 10 x 10^9/L without peripheral blasts in blood or bone marrow.
Partial Hematologic Response/Partial Remission (PR):
Increase in neutrophil by 50% + above 10^9/L for neutropenia)
Clinical Improvement (CI):
Increase in Neutrophil count, hemoglobin, platelet count or reduction in blood/marrow blasts.
Measured: Every cycle of treatment for 6 cycles. Each cycle is 28 days.

Secondary outcomes (3)

Number of Participants With Treatment Related Adverse Events.
Adverse events (AE) that are classified as either possibly, probably, or definitely related to study treatment according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE version 3.0). The maximum grade for each type of AE will be recorded for each patient. The number of participants with grade 3 or higher adverse events at least possibly related to study treatment are reported here.
Measured: During treatment and every 6 months until 3 years from registration or progression.
Duration of Response Time
Duration of response is defined as the date at which the patient's objective status is first noted to be a CR, PR or CI to the date progression is documented (if one has occurred) or to the date of last follow-up(for those patients who have not progressed).
Measured: Time from response to disease progression, intolerance of study drug, or death.
Time to Response
The time to response is defined as the time from study registration to the first date at which the patient's objective status was classified as a response (CR, PR or CI). In patients who do not achieve a response, time to response will be censored at the patient's last evaluation date. The distribution for each of these event-time variables (duration of response and time to response) will be estimated by Kaplan-Meier curves.
Measured: Time from registration to the first date of response within twelve 28-day cycles of treatment.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 200812 Dec 2019

First posted30 Apr 2008 (estimated)
Study startMay 2008
Primary completion7 Jul 2010
Study completion12 Dec 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Chronic Myeloproliferative DisordersStudies of the same condition, open and under way.
More trials run by Mayo ClinicThe 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 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 77 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00669578
Sponsor's protocol ID: MC078B
Other IDs: P30CA015083, MC078B, NCI-2009-01331, 07-005317, PO-MMM-PI-0007
Status last verified: Dec 2019
First submitted: 29 Apr 2008
Last updated: 30 Dec 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 1
Vididencel in CML-CP Patients With MRD
CML (Chronic Myelogenous Leukemia)
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
RecruitingObservational study
HPC Offered for PRESERVE Expansion
Bone Marrow Transplant (BMT)
Not yet recruitingPhase 2
Ropeginterferon Alfa-2b for the Treatment of Myelodysplastic Syndrome/Myeloproliferative Neoplasm Overlap Syndromes and Chronic Myelomonocytic Leukemia
Atypical Chronic Myeloid Leukemia, Chronic Myelomonocytic Leukemia
RecruitingObservational study
Collecting Blood Samples From Patients With and Without Cancer to Evaluate Tests for Early Cancer Detection
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia

All Chronic Myeloproliferative Disorders trials

Study at a glance

From the registry record, last updated by the sponsor on 30 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I/II, Prospective, Open-Label Study to Determine the Safety and Efficacy of CC-4047 in Patients With Primary, Post Polycythemia Vera, or Post Essential Thrombocythemia Myelofibrosis®
ClinicalTrials.gov ID: NCT00669578
Acronym / sponsor ID: MC078B
Conditions: Chronic Myeloproliferative Disorders, Secondary Myelofibrosis
Keywords: secondary myelofibrosis, polycythemia vera, essential thrombocythemia, primary myelofibrosis
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 77 participants (actual)
Lead sponsor: Mayo ClinicUniversity, hospital or other
Collaborators: National Cancer Institute (NCI)
Study start: May 2008 (actual)
Primary completion: 7 Jul 2010 (actual)
Study completion: 12 Dec 2019 (actual)
First posted: 30 Apr 2008 (estimated)
Results: Posted 9 May 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

PURPOSE: This trial is studying the side effects and best dose of CC-4047 and to see how well it works in treating patients with myelofibrosis.

Detailed description

OBJECTIVES:

Phase I:

Primary

To determine the Maximum Tolerated Dose of CC-4047 in the treatment of Primary, Post Polycythemia Vera, or Post Essential Thrombocythemia Myelofibrosis (PMF, post-PV MF, or post-ET MF).

Phase II:

Primary

Best overall response as determined by International Working Group Criteria over the first 6 cycles (168 days) of study treatment.

Secondary

Safety (type, frequency, severity [National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0] of adverse events (AEs), and relationship of AEs to CC-4047.
Duration of response.
Time to response.
Best overall response as determined by International Working Group Criteria over the first 12 cycles (336 days) of study treatment.

OUTLINE: Patients receive oral CC-4047. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 28 days and then every 6 months for up to 3 years.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
CC-4047	Experimental	Drug: CC-4047

Who may qualify

Ages: 18 to 120 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

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
CC-4047CC-4047: taken orally each day in a 28 day cycle.	Drug	CC-4047

Primary outcome

Determine the Maximum Tolerated Dose of CC-4047
Time frame: The first 28-day cycle of treatment.
Starting at a dose level of 2.5 mg/d on days 1-21 in every 28 day cycle, participants were accrued in cohorts of three to assess dose limiting toxicities (DLT) and determine the maximum tolerated dose (MTD). Dose escalation at increments of 0.5 mg/d was done if no subject had a DLT (a grade 4 or higher hematologic toxicity or a grade 3 or higher febrile neutropenia or a grade 3 or higher non-hematologic toxicity) in cycle 1. Subsequent cohorts were treated until the maximum tolerated dose (MTD) was reached (dose level before that which results in a DLT in >1 of 6 subjects). Subsequent participants were treated at the MTD, those without response at the MTD after 3 cycles were lowered to the minimal efficacious dose (MED) of 0.5 mg daily. Here, we are reporting the percentage of participants in Phase I with a DLT at each dose level.
Best Overall Response Over the First 6 Cycles of Treatment
Time frame: Every cycle of treatment for 6 cycles. Each cycle is 28 days.
Response evaluation: Complete Remission (CR): Neutrophil count between 1 to 10 x 10^9/L without peripheral blasts in blood or bone marrow. Partial Hematologic Response/Partial Remission (PR): Increase in neutrophil by 50% + above 10^9/L for neutropenia) Clinical Improvement (CI): Increase in Neutrophil count, hemoglobin, platelet count or reduction in blood/marrow blasts.

3 secondary outcomes

Number of Participants With Treatment Related Adverse Events.
Time frame: During treatment and every 6 months until 3 years from registration or progression.
Duration of Response Time
Time frame: Time from response to disease progression, intolerance of study drug, or death.
Time to Response
Time frame: Time from registration to the first date of response within twelve 28-day cycles of treatment.

Results and safety

Results posted to the registry on 9 May 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Phase I	12	12
Phase II	65	65

Primary outcome: Determine the Maximum Tolerated Dose of CC-4047

Time frame: The first 28-day cycle of treatment.. Number. Unit: percentage of participants with DLT

Measure	Phase I n = 12	Phase II n = 0
2.5 mg/day	0	–
3.0 mg/day	0	–
3.5 mg/day	66	–

Population analysed: None of the Phase II participants were evaluable for this endpoint. For the Phase I portion of this study, three participants were accrued at a 2.5 mg/day dose level, six at the 3.0 mg/day dose level, and three at the 3.5 mg/day dose level.

Primary outcome: Best Overall Response Over the First 6 Cycles of Treatment

Time frame: Every cycle of treatment for 6 cycles. Each cycle is 28 days.. Number. Unit: participants

Measure	Phase II n = 65	Phase I n = 0
Complete Remission	0	–
Partial Remission	0	–
Clinical Improvement	9	–

Population analysed: None of the participants from the Phase I cohort were analyzed for this endpoint. All 65 Phase II participants were evaluable for this endpoint and included in the analysis.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: Every 28 day cycle while on treatment (up to 12 cycles).. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Phase II	19 of 65 (29.2%)	65 of 65 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Dec 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Chronic Myeloproliferative Disorders

RecruitingPhase 1
Vididencel in CML-CP Patients With MRD
CML (Chronic Myelogenous Leukemia)
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
RecruitingObservational study
HPC Offered for PRESERVE Expansion
Bone Marrow Transplant (BMT)
Not yet recruitingPhase 2
Ropeginterferon Alfa-2b for the Treatment of Myelodysplastic Syndrome/Myeloproliferative Neoplasm Overlap Syndromes and Chronic Myelomonocytic Leukemia
Atypical Chronic Myeloid Leukemia, Chronic Myelomonocytic Leukemia
RecruitingObservational study
Collecting Blood Samples From Patients With and Without Cancer to Evaluate Tests for Early Cancer Detection
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia

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.

Ruben A. Mesa, MD principal investigator

Mayo Clinic

Ayalew Tefferi, MD study chair

Mayo Clinic

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing CC-4047 in people with Chronic Myeloproliferative Disorders and Secondary Myelofibrosis, run by Mayo Clinic 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?

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 30 Dec 2019. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 May 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Determine the Maximum Tolerated Dose of CC-4047 (time frame: The first 28-day cycle of treatment.). 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?

On the ClinicalTrials.gov record for NCT00669578.

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 30 Dec 2019.