Pomalidomide for Lenalidomide for Failures
The purpose of this clinical research study is to evaluate the safety and effectiveness (good and bad effects) of pomalidomide given as part of a combination therapy that include more than just steroids to treat subjects with relapsed (subjects whose disease came back) or refractory (subjects whose disease did not respond to past treatment) multiple myeloma (MM).
Pomalidomide (alone or in combination with dexamethasone) has been approved by the United States Food and Drug Administration (FDA) for the treatment of MM patients who have received at least two prior therapies, including lenalidomide and bortezomib, and have demonstrated disease progression on or within 60 days of completion of their last therapy. However, the use of pomalidomide in combination with other drugs used to treat MM, such as chemotherapeutic agents and proteasome inhibitors, is currently being tested and is not approved. Pomalidomide is in the same drug class as thalidomide and lenalidomide. Like lenalidomide, pomalidomide is a drug that alters the immune system and it may also interfere with the development of small blood vessels that help support tumor growth. Therefore, in theory, it may reduce or prevent the growth of cancer cells. The testing done with pomalidomide thus far has shown that it is well-tolerated and effective for subjects with MM both on its own and in combination with dexamethasone. Using another drug class, namely proteasome inhibitors, we have demonstrated that simply replacing a proteasome inhibitor with another in an established anti-myeloma treatment regimen can frequently overcome resistance regardless of the other agents that are part of the anti-myeloma regimen. Importantly, the toxicity profile of the new combinations closely resembled that of the proteasome inhibitor administered as a single agent. Based on this experience, we hypothesize that the replacement of lenalidomide with pomalidomide will yield similar results in a similar relapsed/refractory MM patient population.
|Multiple Myeloma||Drug: POM Drug: Steroids Drug: PLD Drug: CFZ Drug: BTZ Drug: CLA Drug: Other drugs||Phase 2|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Phase 2 Study of Pomalidomide as a Replacement for Lenalidomide for Multiple Myeloma Patients Relapsed or Refractory to a Lenalidomide-Containing Combination Regimen|
- Maximum Tolerated Dose (MTD) [ Time Frame: Cycles 1-3 for selected regimens (up to 3 months) ]
MTD will be determined for any ≥ three-drug combinations other than:
bortezomib + steroids + lenalidomide; carfilzomib + steroids + lenalidomide; clarithromycin + steroids + lenalidomide; cyclophosphamide + steroids + lenalidomide pegylated liposomal doxorubicin (PLD) + lenalidomide with or without steroids
- Number of subjects with adverse events [ Time Frame: up to 36 months ]Adverse events will be graded via the Common Terminology Criteria for Adverse Events (CTCAE) v 4.03 criteria.
- Overall Response Rate [ Time Frame: up to 36 months ]Overall response rate (ORR): complete response (CR)+ very good partial response (VGPR) + partial response (PR)
- Clinical Benefit Rate (CBR) [ Time Frame: up to 36 months ]CBR=ORR + minor response (MR)
- Time to Progression [ Time Frame: time from initiation of therapy to progressive disease (assessed at least over 36 months) ]
- Progression-free survival (PFS) [ Time Frame: time from initiation of therapy to progressive disease or death from any cause, whichever comes first (assessed at least over 36 months) ]
- Time to first response (TTP) [ Time Frame: time from initiation of therapy to the first evidence of a confirmed response (up to 36 months) ]
- Duration of response (DOR) [ Time Frame: time from the first response (> PR) to progressive disease (assessed at least over 36 months) ]
- Overall survival (OS) [ Time Frame: time from initiation of therapy to death from any cause or last follow-up visit (assessed at least over 36 months). ]
|Study Start Date:||August 2014|
|Estimated Study Completion Date:||August 2017|
|Estimated Primary Completion Date:||February 2017 (Final data collection date for primary outcome measure)|
Experimental: A: POM 4mg+Steroids+(CFZ, BTZ, CY or CLA)
POM 4 mg PO days 1-21 Steroids at the same dose and on the same days as the patient's lenalidomide-containing treatment (it varies for each subject).
BTZ (bortezomib)at the same dose and on the same days as the patient's lenalidomide-containing treatment (it varies for each subject).
CFZ (carfilzomib) at the same dose and on the same days as the patient's lenalidomide-containing treatment (it varies for each subject).
CLA (clarithromycin) at the same dose and on the same days as the patient's lenalidomide-containing treatment (it varies for each subject).
CY (cyclophosphamide) at the same dose and on the same days as the patient's lenalidomide-containing treatment (it varies for each subject).
Other Names:Drug: Steroids
Other Names:Drug: CFZ
Other Names:Drug: BTZ
Other Names:Drug: CLA
Other Name: Clarithromycin
Experimental: B: POM 3mg+PLD with or without steroids
POM 3mg; POM 3 mg PO days 1-21 Steroids (if the patient had received them) at the same dose and on the same days as the patient's lenalidomide-containing treatment (it varies for each subject).
PLD at the same dose and on the same days as the patient's lenalidomide-containing treatment (it varies for each subject).
Other Names:Drug: Steroids
Other Names:Drug: PLD
Other Name: Pegylated liposomal doxirrubicin
Experimental: C: POM MTD + other drugs
POM at escalating doses of 2, 3 or 4 mg All other agents, at the same dose and on the same days as the patients were receiving them in the lenalidomide-containing regimen they had failed
POM at the MTD All other agents, at the same dose and on the same days as phase 1
Other Names:Drug: Other drugs
This is a phase 2, multicenter, open-label and non-randomized study to evaluate the efficacy and safety of pomalidomide as a replacement for lenalidomide among MM patients who have failed lenalidomide-containing regimens that include more than steroids within 6 months of their last dose of lenalidomide. Pomalidomide will replace lenalidomide in a combination regimen containing an alkylating agent (cyclophosphamide), anthracycline (doxorubicin or PLD), proteasome inhibitor (bortezomib or carfilzomib) and/or a glucocorticosteroid (prednisone, dexamethasone or methylprednisolone). Pomalidomide will be administered on days 1-21 of a 28-day cycle, whereas other drugs (anthracyclines, proteasome inhibitors, steroids or alkylating agents except melphalan) will be administered using the same schedule(s), dose(s) and drug combination as the last lenalidomide containing regimen that the patient received and failed. This study will enroll patients resistant to a lenalidomide-containing combination regimen as demonstrated by PD while being treated or that has relapsed within 6 months of the last dose of lenalidomide in their last lenalidomide-containing combination regimen or while on lenalidomide or lenalidomide and steroid maintenance therapy. Forty-five patients will be enrolled in the study.
The study consists of: 1) a screening period; 2) up to eight 28-day, treatment cycles; 3) a final assessment to occur 28 days after the end of the last treatment cycle; and 4) a follow-up period.Subjects eligible for this study will receive treatment with study drug for a maximum of eight 28-day treatment cycles, depending on the schedule of their last lenalidomide containing regimen. Subjects are to be treated to a maximum response (lowest level of paraprotein) plus 1 additional cycle, without exceeding a total of 8 cycles, or complete 8 cycles of therapy without progressing (PD).
Please refer to this study by its ClinicalTrials.gov identifier: NCT02188368
|Contact: Carley E Turneremail@example.com|
|Contact: Noemi Silagan, MD||310-623-1209 ext firstname.lastname@example.org|
|United States, California|
|James R. Berenson, MD, Inc.||Recruiting|
|West Hollywood, California, United States, 90069|
|Contact: Regina Swift, RN 310-623-1222 email@example.com|
|Contact: James R. Berenson, MD 310-623-1214 firstname.lastname@example.org|
|Principal Investigator: James Berenson, MD|
|Principal Investigator:||James R Berenson, MD||James R. Berenson MD, Inc.|