Phase II Multicenter, Open-label, Single Arm Clinical Study of Pomalidomide and dexamethasonE and Cyclophosphamide

NCT02046915 | Completed Phase 2 DMC

• 1 other identifier: 2013-003678-29
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Highest treatment efficacy in patients with refractory myeloma may be achieved with regimens combining novel agents and alkylating agents. However, in applying this approach the patients are at substantial risks of a critical myelosuppression. Pomalidomide demonstrates significant activity in combination with Dexamethasone in relapsed or refractory multiple myeloma. This trial is an attempt to further improve the efficacy of Pomalidomide/Dexamethasone as well as to balance efficacy and toxicity. Integration of Cyclophosphamide in the treatment in case of suboptimal response or first evidence of progressive disease has the aim to significantly increase duration of treatment that should have a positive impact on PFS. It is furthermore an attempt to optimize the potential of Pomalidomide in the antimyeloma efficacy. Based on the recent findings, that myeloma is a disease with a wide clonal heterogeneity, combination treatment in case of suboptimal myeloma control might lead to a more effective suppression especially of aggressive subclones and might reduce early resistance. In addition, with the goal of keeping the individual patient as long as possible under an effective IMiD treatment, the potential of the drug might be optimized according to the current view of maintenance treatment resulting ideally in an outgrowth of indolent clones in the bone marrow niche.

Conditions

Relapsed or Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• response rate

  two years

Secondary Outcomes (1)

• progression free survival of Pomalidomide in combination with low-dose Dexamethasone and intravenous Cyclophosphamide

  two years

Study Arms (1)

Pomalidomide, Dexamethasone, Cyclophosphamide

EXPERIMENTAL

1. Pomalidomide administered orally at the starting dose of 4 mg/day on Days 1-21 of a 28-day cycle 2. Low-dose Dexamethasone administered orally at the starting dose of 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15, and 22 of a 28-day cycle 3. Cyclophosphamide administered intravenously 500 mg/m² on Days 1 and 15 of a 28-day cycle

Drug: Imnovid (pomalidomide); Drug: Dexamethasone; Drug: Endoxan (Cyclophosphamide)

Interventions

Imnovid (pomalidomide) DRUG

Also known as: Pomalyst

Pomalidomide, Dexamethasone, Cyclophosphamide

Dexamethasone DRUG

Pomalidomide, Dexamethasone, Cyclophosphamide

Endoxan (Cyclophosphamide) DRUG

Pomalidomide, Dexamethasone, Cyclophosphamide

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must be ≥ 18 years at the time of signing the informed consent.
• Understand and voluntarily sign an informed consent prior to any study related assessments/procedures are conducted.
• Able to adhere to the study visit schedule and other protocol requirements.
• Subjects must have documented diagnosis of multiple myeloma and have measurable disease (serum M-protein ≥ 0.5 g/dL or urine M-protein ≥ 200 mg/24 hours). In case of oligosecretory myeloma: involved FLC level ≥ 10 mg/dl, provided sFLC ratio is abnormal.
• Subjects must have had at least two prior anti-myeloma regimens (incl. bortezomib and lenalidomide) and must have been progressed under the last prior treatment. Induction therapy followed by ASCT and consolidation/ maintenance will be considered as one regimen.
• ECOG performance status score of 0, 1, or 2.
• Females of childbearing potential (FCBP1) must agree:
• to utilize two reliable forms of contraception simultaneously or practice complete abstinence from heterosexual contact for at least 28 days before starting study drug, while participating in the study (including dose interruptions), and for at least 28 days after study treatment discontinuation and must agree to regular pregnancy testing during this timeframe, to abstain from breastfeeding during study participation and 28 days after study drug discontinuation.
• Males must agree: to use a condom during any sexual contact or practice complete abstinence from heterosexual contact with a pregnant female and a FCBP while participating in the study, during dose interruptions and for 28 days following discontinuation from this study, even if he has undergone a successful vasectomy, to refrain from donating semen or sperm while on Pomalidomide and for 28 days after discontinuation from this study treatment.
• All subjects must agree to refrain from donating blood while on study drug and for 28 days after discontinuation from this study treatment.
• All subjects must agree not to share medication.

You may not qualify if:

• Any of the following laboratory abnormalities: Absolute neutrophil count (ANC) \< 1,000/μL.
• Subject with platelet count 30,000/µL are not eligible regardless of the percentage of plasma cells in the bone marrow. For subject with platelet count \> 30,000/µL and \< 75,000/µL, percentage of plasma cells in bone marrow should be 50%.
• Corrected serum calcium \> 14 mg/dL (\> 3.5 mmol/L).
• Hemoglobin \< 8 g/dL (\< 4.9 mmol/L; prior RBC transfusion or recombinant human erythropoietin use is permitted).
• Serum SGOT/AST or SGPT/ALT \> 3.0 x upper limit of normal (ULN) except due to multiple myeloma.
• Serum total bilirubin \> 2.0 mg/dL (34.2 μmol/L); or \> 3.0 x ULN for subjects with hereditary benign hyperbilirubinemia.
• GFR \< 30 ml/min or patient requiring hemodialysis
• Prior history of malignancies, other than MM, unless the subject has been free of the disease for ≥ 5 years. Exceptions include the following:
• Basal or squamous cell carcinoma of the skin
• Carcinoma in situ of the cervix or breast
• Incidental histological finding of prostate cancer (TNM stage of T1a or T1b).
• Previous therapy with Pomalidomide.
• Hypersensitivity to thalidomide, lenalidomide, or Dexamethasone (this includes ≥ Grade 3 rash during prior thalidomide or lenalidomide therapy).
• Peripheral neuropathy ≥ Grade 2.
• Subjects who received an allogeneic bone marrow or allogeneic peripheral blood stem cell transplant less than 12 months prior to initiation of study treatment and who have not discontinued immunosuppressive treatment for at least 4 weeks prior to initiation of study treatment and are currently dependent on such treatment.

Sponsors & Collaborators

• University Hospital Tuebingen: lead

Study Sites (1)

University Hospital

Tübingen, Germany

Location

MeSH Terms

Conditions

Recurrence; Multiple Myeloma

Interventions

pomalidomide; Dexamethasone; Cyclophosphamide

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Plasma Cell; 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

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Design

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

Study Record Dates

• First Submitted: January 22, 2014
• First Posted: January 28, 2014
• Study Start: April 1, 2014
• Primary Completion: August 17, 2016
• Study Completion: August 17, 2017
• Last Updated: October 30, 2017

Record last verified: 2016-10

Locations

DE (1)