CC-4047 in Treating Patients With Myelofibrosis

NCT00669578 | Completed Phase 1 Results DMC

• 5 other identifiers: MC078BP30CA015083NCI-2009-0133107-005317PO-MMM-PI-0007
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Chronic Myeloproliferative Disorders; Secondary Myelofibrosis

Keywords

secondary myelofibrosis; polycythemia vera; essential thrombocythemia; primary myelofibrosis

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Every cycle of treatment for 6 cycles. Each cycle is 28 days.

Secondary Outcomes (3)

• Number of Participants With Treatment Related Adverse Events.

  During treatment and every 6 months until 3 years from registration or progression.

• Duration of Response Time

  Time from response to disease progression, intolerance of study drug, or death.

• Time to Response

  Time from registration to the first date of response within twelve 28-day cycles of treatment.

Study Arms (1)

CC-4047

EXPERIMENTAL

Drug: CC-4047

Interventions

CC-4047 DRUG

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

CC-4047

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Myeloproliferative Disorders; Polycythemia Vera; Thrombocythemia, Essential; Primary Myelofibrosis

Interventions

pomalidomide

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms; Blood Coagulation Disorders; Thrombocytosis; Blood Platelet Disorders; Hemorrhagic Disorders

Results Point of Contact

• Title: Ayalew Tefferi, M.D.
• Organization: Mayo Clinic

tefferi.ayalew@mayo.edu

Study Officials

• Ruben A. Mesa, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

• Ayalew Tefferi, MD

  Mayo Clinic

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2008
• First Posted: April 30, 2008
• Study Start: May 1, 2008
• Primary Completion: July 7, 2010
• Study Completion: December 12, 2019
• Last Updated: December 30, 2019
• Results First Posted: May 9, 2014

Record last verified: 2019-12

Locations

US (1)