Pomalidomide in Combination With High Dose Dexamethasone and Oral Cyclophosphamide

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:
NCT01432600
First received: September 9, 2011
Last updated: August 20, 2014
Last verified: August 2014
  Purpose

The main purpose of this study is to see whether pomalidomide can help people with myeloma. Researchers also want to find out if pomalidomide is safe and tolerable.


Condition Intervention Phase
Myeloma
Drug: Pomalidomide
Drug: Dexamethasone
Drug: Cyclophosphamide
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Evaluation of Pomalidomide in Combination With High Dose Dexamethasone and Oral Cyclophosphamide in Patients With Relapsed and Refractory Myeloma

Resource links provided by NLM:


Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:
  • Phase I - Maximum Tolerated Dose [ Time Frame: 28 Days ] [ Designated as safety issue: No ]
    For the phase I, the primary objective is to determine the maximum tolerated dose of oral weekly cyclophosphamide in combination with pomalidomide and dexamethasone.

  • Phase II - Number of Participants With Desired Response [ Time Frame: 24 Months ] [ Designated as safety issue: No ]
    For the phase II, to determine compare the efficacy (best response rate using the uniform response criteria by the International Myeloma Working Group (IMWG) of pomalidomide in combination with high dose dexamethasone with or without cyclophosphamide in patients with relapsed and refractory myeloma


Secondary Outcome Measures:
  • Phase II - Number of Participants With Progression Free Survival (PFS) [ Time Frame: 24 Months ] [ Designated as safety issue: No ]
    To compare the progression free survival of both combination therapies in patients with relapsed and refractory multiple myeloma

  • Phase II - Number of Participants With Overall Survival (OS) [ Time Frame: 24 Months ] [ Designated as safety issue: No ]
    To determine the overall survival of patients treated with these combinations

  • The Number of Participants With Adverse Events (AEs) [ Time Frame: 24 Months ] [ Designated as safety issue: Yes ]
    To determine safety of this combination in this patient population as assessed by the National Cancer Institute Common Terminology Criteria (NCI CTC) version 4.0


Enrollment: 80
Study Start Date: November 2011
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose Escalation of Cyclophosphamide

Phase I: Pomalidomide high dose dexamethasone and oral cyclophosphamide:

Pomalidomide 4 mg PO days 1-21 of a 28 days cycle

Dexamethasone 40* mg PO days 1- 4, 15-18 of a 28 days cycle for the first 4 cycles and subsequently 40 mg PO Days 1,8,15, 22

Cyclophosphamide up to 500 mg PO days 1, 8, 15

Aspirin 81 mg PO daily

*Patients who are older than 75 years of age, will receive 20 mg of dexamethasone instead of 40 mg of dexamethasone on the schedules noted above given the impaired tolerance for this age group to high dose dexamethasone.

Drug: Pomalidomide
Once the maximum tolerated dose (MTD) of oral weekly cyclophosphamide in combination with pomalidomide and dexamethasone is determined, we will proceed with the second phase of the trial which is a randomized phase II study comparing pomalidomide and dexamethasone and pomalidomide, dexamethasone and oral weekly cyclophosphamide delivered at the MTD determined in the phase I study.
Other Name: CC-4047
Drug: Dexamethasone
Once the maximum tolerated dose (MTD) of oral weekly cyclophosphamide in combination with pomalidomide and dexamethasone is determined, we will proceed with the second phase of the trial which is a randomized phase II study comparing pomalidomide and dexamethasone and pomalidomide, dexamethasone and oral weekly cyclophosphamide delivered at the MTD determined in the phase I study.
Drug: Cyclophosphamide
Once the maximum tolerated dose (MTD) of oral weekly cyclophosphamide in combination with pomalidomide and dexamethasone is determined, we will proceed with the second phase of the trial which is a randomized phase II study comparing pomalidomide and dexamethasone and pomalidomide, dexamethasone and oral weekly cyclophosphamide delivered at the MTD determined in the phase I study.
Active Comparator: Pomalidomide and Dexamethasone

Randomized Phase II - Pomalidomide high dose dexamethasone: Arm A

Pomalidomide 4 mg PO days 1-21 of a 28 days cycle

Dexamethasone 40* mg PO Days 1,8,15, 22

Aspirin 81 mg PO daily

*Patients who are older than 75 years of age, will receive 20 mg of dexamethasone instead of 40 mg of dexamethasone on the schedules noted above given the impaired tolerance for this age group to high dose dexamethasone.

Drug: Pomalidomide
Once the maximum tolerated dose (MTD) of oral weekly cyclophosphamide in combination with pomalidomide and dexamethasone is determined, we will proceed with the second phase of the trial which is a randomized phase II study comparing pomalidomide and dexamethasone and pomalidomide, dexamethasone and oral weekly cyclophosphamide delivered at the MTD determined in the phase I study.
Other Name: CC-4047
Drug: Dexamethasone
Once the maximum tolerated dose (MTD) of oral weekly cyclophosphamide in combination with pomalidomide and dexamethasone is determined, we will proceed with the second phase of the trial which is a randomized phase II study comparing pomalidomide and dexamethasone and pomalidomide, dexamethasone and oral weekly cyclophosphamide delivered at the MTD determined in the phase I study.
Active Comparator: Pomalidomide, Dexamethasone, Cyclophosphamide

Randomized Phase II - Pomalidomide high dose dexamethasone and oral cyclophosphamide: Arm B

Pomalidomide 4 mg PO days 1-21 of a 28 days cycle

Dexamethasone 40* mg PO Days 1,8,15, 22

Cyclophosphamide 400 mg PO days 1, 8, 15

Aspirin 81 mg PO daily

*Patients who are older than 75 years of age, will receive 20 mg of dexamethasone instead of 40 mg of dexamethasone on the schedules noted above given the impaired tolerance for this age group to high dose dexamethasone.

Drug: Pomalidomide
Once the maximum tolerated dose (MTD) of oral weekly cyclophosphamide in combination with pomalidomide and dexamethasone is determined, we will proceed with the second phase of the trial which is a randomized phase II study comparing pomalidomide and dexamethasone and pomalidomide, dexamethasone and oral weekly cyclophosphamide delivered at the MTD determined in the phase I study.
Other Name: CC-4047
Drug: Dexamethasone
Once the maximum tolerated dose (MTD) of oral weekly cyclophosphamide in combination with pomalidomide and dexamethasone is determined, we will proceed with the second phase of the trial which is a randomized phase II study comparing pomalidomide and dexamethasone and pomalidomide, dexamethasone and oral weekly cyclophosphamide delivered at the MTD determined in the phase I study.
Drug: Cyclophosphamide
Once the maximum tolerated dose (MTD) of oral weekly cyclophosphamide in combination with pomalidomide and dexamethasone is determined, we will proceed with the second phase of the trial which is a randomized phase II study comparing pomalidomide and dexamethasone and pomalidomide, dexamethasone and oral weekly cyclophosphamide delivered at the MTD determined in the phase I study.

Detailed Description:

There are two parts to this study:

  • The first part of this study (Phase 1) will determine a safe dose of the medication cyclophosphamide in combination with pomalidomide and dexamethasone.
  • Once the safest dose has been determined, this study (Phase 2) will look to see the difference in effectiveness of pomalidomide in combination with high dose dexamethasone with or without cyclophosphamide for the treatment of patients who have myeloma, which has relapsed to or become refractory (not responding) to prior treatment.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have relapsed or refractory multiple myeloma. Refractory disease is defined as patients who experience disease progression on active therapy or within 60 days after the discontinuation of therapy. Relapsed disease is defined as achievement of at least a partial response followed by disease progression after 60 days of discontinuing active therapy.
  • Must have measurable disease as assessed by one of the following criteria: Serum monoclonal protein ≥ 0.5 g/dL by protein electrophoresis; >200 mg of monoclonal protein in the urine on 24 hour electrophoresis; Serum immunoglobulin free light chain ≥ 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
  • Must have received at least 2 prior therapies to include prior immunomodulatory drug (lenalidomide) and the patient must be refractory to lenalidomide (defined as progressive disease during active therapy or within 60 days of discontinuation of therapy). All previous cancer chemotherapy (bisphosphonates are not included), including surgery, must have been discontinued ≥2 weeks prior to first dose of study drug. Prior radiotherapy must have been completed > 2 weeks prior to the start of study drug unless the radiation field would not impact marrow reserve in the opinion of the investigator.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (Karnofsky ≥60%
  • Must have acceptable organ function: total bilirubin less than 1.5 mg/dL; aspartic transaminase (AST)/alanine transaminase (ALT) ≤2.5 X institutional upper limit of normal (ULN); serum creatinine < 3mg/dL
  • Patients must have adequate hematologic function as evidenced by the following:

For the Phase I study:

Absolute neutrophil count (ANC) ≥ 1000 per mm³ Platelet count ≥ 50,000 per mm³ For the Phase II portion, patients with greater than 50% bone marrow plasmacytosis will be allowed to enter the trial if the platelet count is greater than 30,000 per mm³ and regardless of baseline absolute neutrophil count if it is felt to be related to active myeloma and if in the opinion of the investigator, growth factor support can result in improvement in the neutrophil count to greater than 1000 per mm³ (growth factor can be used during screening).

  • Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting pomalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking pomalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a vasectomy.
  • Ability to understand and the willingness to sign a written informed consent document
  • Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to acetylsalicylic acid (ASA) may use warfarin or low molecular weight heparin).
  • All study participants must be registered into the mandatory POMALYST REMS™ program, and be willing and able to comply with the requirements of the POMALYST REMS™ program.

Exclusion Criteria:

  • Patients who have had chemotherapy or radiotherapy within 2 weeks (see Inclusion Criteria above) or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier (except for neuropathy).
  • Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from signing the informed consent form
  • Any condition, including the presence of laboratory abnormalities, which places the patient 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
  • Known positive for human immunodeficiency virus (HIV) or infectious hepatitis, type A, B or C
  • May not be receiving any other investigational agents
  • Pregnant or breast feeding females (Lactating females must agree not to breast feed while taking pomalidomide).
  • Patients with prior pomalidomide therapy (greater than 1 cycle) are excluded.
  • Another active malignancy requiring treatment within the next 12 months, with the exception of basal cell skin cancer, in situ cervical cancer, in situ breast cancer and asymptomatic prostate cancer
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (except simple urinary tract or upper respiratory tract infection), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Inability to comply with the protocol requirements or participation in any other clinical study
  • Corticosteroid therapies of >20 mg/day prednisone, >4 mg/day dexamethasone, >80 mg/day hydrocortisone, or equivalent
  • Allogeneic stem cell/bone marrow transplant within 12 months of first dose of study drug or active graft versus host disease
  • Patients with existing peripheral neuropathy grade >2
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01432600

Locations
United States, California
University of California San Francisco
San Francisco, California, United States, 94143
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612
United States, New York
Mount Sinai School of Medicine, The Tisch Cancer Institute
New York, New York, United States, 10029-6574
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Celgene Corporation
Investigators
Principal Investigator: Rachid Baz, M.D. H. Lee Moffitt Cancer and Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT01432600     History of Changes
Other Study ID Numbers: MCC-16705, PO-MM-PI-0039
Study First Received: September 9, 2011
Last Updated: August 20, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
Multiple Myeloma
Relapsed
Refractory
Corticosteroids

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Thalidomide
Pomalidomide
Dexamethasone
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014