Continuous Versus Intermittent Dosing Regimens for Pomalidomide in Relapsed/Refractory Multiple Myeloma

NCT01319422 | Completed Phase 2 Results

• 1 other identifier: HIC 1011007607
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Lenalidomide has clinical activity in myeloma. The closely related compound, Pomalidomide, may have clinical activity in patients who have previously been treated with lenalidomide and who no longer respond to it. The mechanism of anti-tumor effects of these drugs has been attributed to several effects including anti-angiogenesis, immune activation, and anti-proliferative effects. Recent studies have suggested that these agents can mediate surprisingly rapid biologic effects on human monocytes and T cells. Our hypothesis is that the proximate effects of these drugs will be sensitive and quantitative surrogates of subsequent effects including activation of tumor antigen specific T cells as well as innate immune cells. Understanding the correlation between the pharmacodynamics of these effects with downstream activation using quantitative assays will facilitate the rational development of pomalidomide as immune-modulatory drug in diverse settings as well as its optimal development in myeloma therapy.

Conditions

Multiple Myeloma

Keywords

myeloma; multiple myeloma; pomalidomide; immunomodulatory

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Response, Analyzed Per International Myeloma Working Group Response Criteria

  All partial and complete responses must be confirmed with another efficacy assessment in no less than 4 weeks apart.

  Efficacy assessments will be made after the first two cycles of therapy (approximately 56 days--each cycle is 28 days)

• Percentage of Participants With Response, Analyzed Per International Myeloma Working Group Response Criteria

  All partial and complete responses must be confirmed with another efficacy assessment in no less than 4 weeks apart.

  After the initial efficacy assessment at the completion of cycle 2 (at approximately 56 days), efficacy assessments will be made after every other cycle (approximately every 56 days).

Secondary Outcomes (3)

• To Compare the Effect of Continuous Versus Intermittent Regimens on F Actin Polymerization in Peripheral Blood Mononuclear Cells and Activation of Tumor Antigen-specific T Cells, as Well as Innate Lymphocytes (Natural Killer or Natural Killer T Cells).

  Research blood draw will be obtained at baseline, and at 2-4 hr (on day 1), 1 wk, and 4 wk after initiation of cycles 1 and 2.

• To Correlate Drug Induced Changes in F Actin Polymerization With Adverse Effects and Clinical Responses.

  Research bone marrow aspirate is obtained at baseline and after completion of 2 cycles of therapy (approximately 56 days)

• To Correlate Drug Induced Changes in F Actin With Cytokine Profile.

  Research blood draw will be obtained at baseline, and at 2-4 hr (on day 1), 1 wk, and 4 wk after initiation of cycles 1 and 2.

Study Arms (2)

Pomalidomide 2 mg/d on 28 days/28 day cycle

EXPERIMENTAL

Drug: Pomalidomide

Pomalidomide 4 mg/d on 21 days/28 day cycle

EXPERIMENTAL

Drug: Pomalidomide

Interventions

Pomalidomide DRUG

Comparison of different dosages and schedules of drug

Also known as: CC-4047

Pomalidomide 2 mg/d on 28 days/28 day cycle; Pomalidomide 4 mg/d on 21 days/28 day cycle

Eligibility Criteria

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

You may qualify if:

• Understand and voluntarily sign an informed consent form.
• Age ≥18 years at the time of signing the informed consent form.
• Able to adhere to the study visit schedule and other protocol requirements.
• Relapsed / Refractory Multiple Myeloma following at least two prior standard therapies including lenalidomide. Induction therapy followed by autologous stem cell transplantation (ASCT) is considered one regimen.
• Patients must be refractory to prior lenalidomide therapy. For the purpose of this protocol, refractory will be defined as history of progression on a regimen containing full or maximally tolerated dose of lenalidomide administered for a minimum of at least one complete cycle of therapy.
• All patients must have measurable disease defined as one or more of the following criteria:
• Serum monoclonal protein greater than 10 g/L, serum immunoglobulin free light chain (FLC) more than 10 mg/dL and an abnormal FLC ratio, urine light-chain excretion \> 200 mg/24 h, measurable soft tissue plasmacytoma that has not been irradiated, or greater than 30% plasma cells in bone marrow.
• All previous cancer therapy, including radiation, hormonal therapy and surgery, must have been discontinued at least 2 weeks prior to treatment in this study.
• Eastern Cooperative Oncology Group (ECOG ) performance status of ≤ 2 at study entry (see Appendix D).
• Laboratory test results within these ranges:
• Absolute neutrophil count ≥ 1.0 x 1000/microliter (uL)
• Platelet count ≥ 75 x 1000/uL
• Serum creatinine ≤ 2.5 mg/dL
• Total bilirubin ≤ 2 mg/dL
• aspartate aminotransferase (AST) (SGOT) and alanine aminotransferase (ALT) (SGPT) ≤ 5 x upper limit of normal (ULN)

You may not qualify if:

• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
• Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking pomalidomide).
• Women of child-bearing potential who are unwilling to use a dual method of contraception; and men who are unwilling to use a condom.
• Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
• Use of any other experimental drug or therapy within 28 days of baseline.
• Known hypersensitivity to thalidomide or lenalidomide.
• The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide, pomalidomide or similar drugs.
• Any prior use of pomalidomide.
• Concurrent use of other anti-cancer agents or treatments.
• Known positive for HIV or active infectious hepatitis, B or C.
• Grade 3 or 4 peripheral neuropathy

Sponsors & Collaborators

• Yale University: lead
• Celgene Corporation: collaborator

Study Sites (1)

Yale University

New Haven, Connecticut, 06520, United States

Location

Related Publications (1)

• Sehgal K, Das R, Zhang L, Verma R, Deng Y, Kocoglu M, Vasquez J, Koduru S, Ren Y, Wang M, Couto S, Breider M, Hansel D, Seropian S, Cooper D, Thakurta A, Yao X, Dhodapkar KM, Dhodapkar MV. Clinical and pharmacodynamic analysis of pomalidomide dosing strategies in myeloma: impact of immune activation and cereblon targets. Blood. 2015 Jun 25;125(26):4042-51. doi: 10.1182/blood-2014-11-611426. Epub 2015 Apr 13.

  PMID: 25869284 DERIVED

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

pomalidomide

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Madhav Dhodapkar, M.D.
• Organization: Yale University

madhav.dhodapkar@yale.edu

203-785-4144

Study Officials

• Madhav Dhodapkar, M.D.

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2011
• First Posted: March 21, 2011
• Study Start: June 1, 2011
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: August 11, 2016
• Results First Posted: August 11, 2016

Record last verified: 2016-06

Locations

US (1)