Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Antineoplastic Agents

All Drugs and Chemicals

Bortezomib

Bortezomib will be administered SC at a dose of 1.0 mg/m2. Doses are to be administered on days 1, 4, 8, and 11 of a 28-day cycle. All other drugs used in combination with the SC bortezomib as well as their doses and schedules will be at the discretion of the Principal Investigator.

Subcutaneous bortezomib

James R Berenson, MD

This is a phase 2, multicenter, open label, nonrandomized study for patients with MM who will receive treatment with a SC bortezomib-containing combination regimen that does not contain thalidomide or vincristine. The patients will be required to have received a prior IV bortezomib containing combination regimen that did not contain thalidomide or vincristine and that differs from the SC bortezomib-containing one. In between the time that the patient received the IV bortezomib-based combination regimen and enrollment onto this study, patients may have received other non-bortezomib-based regimens as long as these treatments did not contain thalidomide or vincristine. This study will enroll patients who have relapsed or have become refractory to their prior IV-administered bortezomib-containing combination regimen as demonstrated by progressive disease while on or following that regimen. Patients must have received 4 doses of a minimum of 1.0 mg/m2 of bortezomib administered IV in no more than 4 weeks per cycle. Patients must have received at least one cycle meeting this definition and have shown progressive disease to be considered eligible. Patients who have relapsed or have become refractory to their most recent IV bortezomib-containing combination regimen are eligible regardless of when they received that regimen, as long as they meet the above criteria.

The study will consist of a screening period, followed by up to eight open label treatment cycles, a final assessment to occur 28 days after the end of the last treatment cycle, and a follow-up period.

Primary Objectives:

• To establish the safety and tolerability of treatment with a SC bortezomib containing combination regimen for MM patients who have demonstrated progressive disease from a prior and different IV bortezomib containing combination regimen:

* To compare the incidence of PN between IV bortezomib and treatment with SC bortezomib in a subsequent anti-MM combination regimen
* To compare the severity of PN between IV bortezomib and treatment with SC bortezomib in a subsequent combination anti-MM regimen

Secondary Objectives:

* To compare the overall response rate \[combined CR + very good partial response (VGPR) + PR + MR\] following treatment with a SC bortezomib-containing combination regimen for MM patients who have demonstrated progressive disease from a prior and different IV bortezomib containing combination regimen
* To compare disease parameters following treatment with a SC bortezomib containing combination regimen for MM patients who have demonstrated progressive disease from a prior and different IV bortezomib containing combination regimen as follows:

  * time to progression
  * progression free survival
  * time to first response
  * duration of response
  * overall survival
* To determine the incidence and severity of injection-site reactions with SC administration of bortezomib

Subcutaneous (SC) Bortezomib-Regimens for Patients With RR MM Failing Prior IV Bortezomib-Containing Regimens

A Phase II Study of Subcutaneous (SC) Bortezomib-Regimens for Patients With Relapsed/Refractory Multiple Myeloma (MM) Failing Prior Intravenous (IV) Bortezomib-Containing Regimens

Definition of incidence: the number of participants enrolled in the study experiencing treatment-emergent peripheral neuropathy. Emergence of peripheral neuropathy is determined via neurological assessment conducted on Day 1 and Day 11 of each treatment cycle as well as during the End of Study visit.

Definition of severity: the severity of any treatment-emergent peripheral neuropathy experienced by a patient on-study. Peripheral neuropathy severity is determined via neurological assessment conducted on Day 1 and Day 11 of each treatment cycle as well as the End of Study visit and is graded on a 0-4 scale based on CTCAE criteria.

Incidence of Peripheral Neuropathy Definition: the number of participants enrolled in the study experiencing treatment-emergent peripheral neuropathy. Emergence of peripheral neuropathy is determined via neurological assessment conducted on Day 1 and Day 11 of each treatment cycle as well as during the End of Study visit.

Compare overall response rate \[combined CR + very good partial response (VGPR) + PR + MR\] and disease parameters \[time to progression, -progression free survival, -time to first response, -duration of response, -overall survival\] following treatment with a SC bortezomib-containing combination regimen for MM patients who have demonstrated progressive disease form a prior or different IV bortezomib-containing combination regimen. Determine incidence and severity of injection-site reactions with CS administration of bortezomib by number of patients with injection site reaction specific adverse events.

Millennium Pharmaceuticals, Inc.

Oncotherapeutics

Bortezomib was administered SC at a dose of 1.0 mg/m2. Doses were administered on days 1, 4, 8, and 11 of a 28-day cycle. When administered subcutaneously, sites for each injection (thigh or abdomen) were rotated and reported. All other drugs used in combination with the SC bortezomib were recorded in the Case Report Forms along with their corresponding doses and schedules.

Subcutaneous Bortezomib

Age, Categorical

Age, Continuous

Gender

United States

Region of Enrollment

The patients were required to have received a prior IV bortezomib containing combination regimen tha

Dr. James Berenson

Patients with MM who received treatment with a SC bortezomib-containing combination

The Primary Objective of This Study Will be to Investigate the Incidence and Severity of Peripheral Neuropathy Caused by a Prior Intravenous VELCADE-containing Regimen in Comparison to That Caused by a Subcutaneous VELCADE-containing Regimen.

Compare Overall Response Rate (CR + VGPR + PR + MR), Compare Disease Parameters, & Determine Incidence and Severity of Injection-site Reactions.

patients with MM who received treatment with a SC bortezomib-containing combination. The patients were required to have received a prior IV bortezomib containing combination regimen that differs from the SC bortezomib-containing treatment.

Overall Study

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Anti-Infective Agents

Dexamethasone

Doxorubicin

Liposomal doxorubicin

Pomalidomide

Dexamethasone acetate

BB 1101

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

Pomalidomide + Pegylated Liposomal Doxorubicin + Dexamethasone in an open label, dose escalation study

Pomalidomide administered to 3 cohorts of subjects at escalating doses of 2 (cohort 1), 3 (cohort 2) and 4 mg/dose (cohort 3) per orem (PO). Doses are to be administered once-a-day, for the first 21 days, as part of a 28-day treatment cycle, followed by a 7-day rest period.

Dexamethasone will be given at a dose of 40 mg/dose IV. Doses are to be administered on days 1, 4, 8, and 11 of the 28-day cycle.

PLD will be given at a dose of 5.0 mg/m2 as a 60 minute IV infusion on Day 1 of Cycle 1 and subsequent doses may be administered over 30 to 60 minutes on Days 4, 8 and 11 of Cycle 1 and on Days 1, 4, 8, and 11 of each subsequent cycle.

Pegylated Liposomal Doxorubicin (PLD)

Dexamethasone will be given at a dose of 40 mg/dose IV. Doses are to be administered on days 1, 4, 8, and 11 of the 28-day cycle.

The purpose of this clinical research study is to evaluate the safety and effectiveness (good and bad effects) of a combination of three different drugs, pomalidomide, pegylated liposomal doxorubicin, and dexamethasone when used to treat relapsed (the disease came back) or refractory (the disease did not respond to past treatment) multiple myeloma. Different dosages (amount of study drug) of pomalidomide are first being tested to determine if there are any side effects or risks associated with combining this study drug with the other two listed. Once the optimal dose is decided on, the study will change its focus to determining the effectiveness of the study drug in this combination.

This is a phase 1/2, multicenter, open label and nonrandomized study to evaluate the efficacy and safety of pomalidomide at daily dosages of 2, 3 or 4 mg in combination with intravenous (IV) dexamethasone at 40 mg/dose and Pegylated Liposomal Doxorubicin (PLD) at 5 mg/m2/dose for subjects with relapsed/refractory multiple myeloma (MM). The study consists of a screening period, followed by up to eight 28 day open label treatment cycles, a final assessment to occur 28 days after the end of the last treatment, and a follow-up period.

Subjects eligible for this study will receive treatment with study drug for a maximum of eight 28 day treatment cycles. Subjects are to be treated to a maximum response plus 2 additional cycles (no more than 8 cycles will be allowed) or complete 8 cycles of therapy without disease progression.

Pomalidomide, dexamethasone and PLD will be administered on the appropriate cycle days as shown below.

Cohort 1 Pomalidomide\* - 2 mg, Dexamethasone\*\* - 40 mg, PLD\*\* - 5 mg/m2

Cohort 2 Pomalidomide\* - 3 mg, Dexamethasone\*\* - 40 mg, PLD\*\* - 5 mg/m2

Cohort 3 Pomalidomide\* - 4 mg, Dexamethasone\*\* - 40 mg, PLD\*\* - 5 mg/m2

\* PO Days 1-21

\*\* IV Days 1, 4, 8 and 11

In all cohorts, if an unacceptable dose limiting toxicities (DLT) is not seen in any of the 3 subjects during the first cycle of any dose level, dose escalation will continue. All subjects in a cohort must complete a minimum of 28 days or a full cycle, whichever is longer, without a DLT before enrollment to the next cohort can begin. If a DLT is identified in 1 subject at any dose level during the first treatment cycle, an additional 3 subjects will be recruited to this dose level. A maximum of 6 subjects may be enrolled in each cohort. If an unacceptable DLT is observed in 2 subjects at any dose level, no further subjects will be recruited to this dose level. The maximum tolerated dose (MTD) will be declared as the highest dose level at which fewer than 33% of subjects experienced an unacceptable DLT. If pomalidomide at 4 mg is reached and fewer than 33% of subjects experience an unacceptable DLT, 4 mg will be accepted as the putative MTD. Once the MTD is established, further enrollment will continue to expand that dose cohort until the total sample size of 40 subjects is reached for the entire study. During the phase 2 portion of this study, subjects enrolled will have relapsed/refractory MM resistant to lenalidomide as demonstrated by progressive disease while on lenalidomide or that has relapsed within 8 weeks of the last dose of lenalidomide.

Pomalidomide, Dexamethasone and Pegylated Liposomal Doxorubicin for Relapsed/Refractory Multiple Myeloma

A Phase 1/2 Study of Pomalidomide, Dexamethasone and Pegylated Liposomal Doxorubicin for Patients With Relapsed/Refractory Multiple Myeloma

Phase 1: To establish the MTD of pomalidomide in combination with dexamethasone and pegylated liposomal doxorubicin

Phase 2: To determine efficacy as evidenced by the best overall response rate (CR + VGPR + PR + MR) following treatment with pomalidomide, dexamethasone and pegylated liposomal doxorubicin

Phase 2: To establish the number of patients with adverse events when using the combination of pomalidomide, dexamethasone and pegylated liposomal doxorubicin

Phase 2: Defined as the time from initiation of therapy to progressive disease

Phase 2: Defined as the time from initiation of therapy to progressive disease or death from any cause, which ever occurs first

Phase 2: Defined as the time from the initiation of therapy to the first evidence of a confirmed response (CR, VGPR, PR or MR)

Phase 2: Defined as the time from first response to progressive disease

Phase 2: Defined as the time from initiation of therapy to death from any cause or last follow-up visit

Celgene Corporation

Thalidomide

Lenalidomide

Bortezomib is replaced with carfilzomib in a combined regimen identical to the patient's previous regimen. Regimen cannot include thalidomide or lenalidomide.

Bortezomib is replaced with carfilzomib in a regimen that includes IMiDs (lenalidomide or thalidomide). Thus, the regimen is carfilzomib in an IMiD-containing regimen.

Carfilzomib will be administered intravenously starting at a dose of 20 mg/m\^2 over 30 minutes for the first cycle and will then be increased to 27, 36 and 45 mg/m2 during cycles 2-4, respectively. Doses will be administered IV once daily on days 1, 2, 8, 9, 15, and 16 of each cycle. Cycles will be 28 days in length.

Combination non-IMiD drug is dosed on the identical schedule and dosage as patient was in previous bortezomib containing regimen.

Maintenance regimen maybe administered if patient does not progress while on study.

Group A: Carfilzomib & Non-IMiD Regimen

Carfilzomib will be administered intravenously starting at a dose of 20 mg/m\^2 over 30 minutes for the first cycle and will then be increased to 27, 36 and 45 mg/m2 during cycles 2-4, respectively. Doses will be administered IV once daily on days 1, 2, 8, 9, 15, and 16 of each cycle. Cycles will be 28 days in length.

Combination IMiD drug is dosed on the identical schedule and dosage as patient was in previous bortezomib containing regimen.

Maintenance regimen maybe administered if patient does not progress while on study.

Group B: Carfilzomib & IMiD containing regimen.

This is a phase I/II multicenter, open label, nonrandomized study for patients with Multiple Myeloma (MM) who will receive treatment with carfilzomib in place of bortezomib using the same bortezomib-containing combination regimen to which a MM patient has progressed while receiving. This study will enroll 45 patients total. These patients will be resistant to bortezomib as demonstrated by progressive disease while on bortezomib or have relapsed within 12 weeks of the last dose of bortezomib in a combination regimen. Patients will be sub-divided into 2 groups in this study, treatments containing (Group A) or not containing immunomodulatory drugs (IMiDs) (Group B). Thirty patient will be enrolled into Group A and 15 patients into Group B for a total of 45 patients. Patients must have received 4 doses of a minimum of 1.0 mg/m\^2 of bortezomib in no more than 4 weeks per cycle. Patients must have received at least one cycle meeting this definition and have shown progressive disease to be considered eligible. Patients who have been refractory to or relapsed within 12 weeks of the last dose of bortezomib in their most recent bortezomib-containing regimen that does not include either thalidomide or lenalidomide are eligible regardless of when patients received that regimen, as long as they meet the above criteria.

Carfilzomib will subsequently replace bortezomib using the patient's most recent bortezomib-containing regimen to which the patient progressed while receiving. Patients will be eligible if they progressed from bortezomib with an alkylating agent (melphalan or cyclophosphamide), an anthracycline (doxorubicin or pegylated liposomal doxorubicin) and/or a glucocorticosteroid (prednisone, dexamethasone or medrol)and IMiD (thalidomide or lenalidomide). The study will consist of a screening period, followed by up to eight open label treatment cycles, a final assessment to occur 28 days after the end of the last treatment cycle, a follow-up period and maintenance cycles of single agent carfilzomib.

Patient who complete the combination treatment period without progressive disease will be eligible for maintenance therapy with single-agent carfilzomib. During maintenance therapy carfilzomib will be administered at the same dose given during the last cycle of combination treatment.

Study of Carfilzomib for Multiple Myeloma Patients Who Are Relapsed/Refractory to Bortezomib-containing Treatments

A Phase I/II Study of Carfilzomib as a Replacement for Multiple Myeloma Patients Failing Bortezomib-containing Regimens

Phase I:

• To establish the maximum tolerated dose (MTD) and determine the dose limiting toxicities (DLT) following treatment.

Phase II:

• To determine the efficacy as assessed by the overall response rate \[CR + VGPR + PR + MR\] and the Time to Progression (TTP) of disease.

Phase I:

Obtain preliminary evidence of efficacy following treatment based on:

* SPEP, UPEP and quantification of serum immunoglobulins
* Bone marrow aspirates \& biopsies
* B2M
* A roentgenographic skeletal survey of bones

Phase II:

Establish the safety \& tolerability following treatment based on:

* Adverse events
* Clinical lab tests
* Vital signs
* Medical history \& body weight measurements
* ECOG performance status
* Concomitant medication usage

Both phases:

Progression Free Survival among patients who continue onto maintenance treatment

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Subcutaneous (SC) Bortezomib-Regimens for Patients With RR MM Failing Prior IV Bortezomib-Containing Regimens	NCT01695330	Multiple Myelom...	Subcutaneous bo...	18 Years -	Oncotherapeutics
Subcutaneous (SC) Bortezomib-Regimens for Patients With RR MM Failing Prior IV Bortezomib-Containing Regimens	NCT01695330	Multiple Myelom...	Subcutaneous bo...	18 Years -	Oncotherapeutics
Pomalidomide, Dexamethasone and Pegylated Liposomal Doxorubicin for Relapsed/Refractory Multiple Myeloma	NCT01541332	Multiple Myelom...	Pomalidomide Pegylated Lipos... Dexamethasone	18 Years -	Oncotherapeutics
Study of Carfilzomib for Multiple Myeloma Patients Who Are Relapsed/Refractory to Bortezomib-containing Treatments	NCT01365559	Multiple Myelom...	Group A: Carfil... Group B: Carfil...	18 Years -	Oncotherapeutics
Subcutaneous (SC) Bortezomib-Regimens for Patients With RR MM Failing Prior IV Bortezomib-Containing Regimens	NCT01695330	Multiple Myelom...	Subcutaneous bo...	18 Years -	Oncotherapeutics

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