A Phase 1/2 interventional study of cyclophosphamide and pegylated liposomal doxorubicin hydrochloride in Refractory Multiple Myeloma, Stage I Multiple Myeloma and Stage II Multiple Myeloma, sponsored by University of Washington. Terminated at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-09-08.
Sponsored by University of Washington · Phase 1/2, Interventional, and Treatment
RATIONALE: Drugs used in chemotherapy, such as pegylated liposomal doxorubicin hydrochloride and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer. Giving pegylated liposomal doxorubicin hydrochloride together with bortezomib, cyclophosphamide, and dexamethasone may kill more cancer cells.
PURPOSE: This phase I/II trial is studying the side effects of giving pegylated liposomal doxorubicin hydrochloride together with bortezomib, cyclophosphamide, and dexamethasone and to see how well it works in treating patients with multiple myeloma
PRIMARY OBJECTIVES:
I. To determine efficacy of this novel combination in newly diagnosed patients with multiple myeloma.
SECONDARY OBJECTIVES:
I. To determine the toxicity of this novel combination regimen in previously treated patients and newly diagnosed patients with multiple myeloma.
OUTLINE:
Patients receive cyclophosphamide intravenously (IV) or orally (PO) over 1 hour, bortezomib IV over 3 minutes, and dexamethasone IV or PO on days 1, 8, and 15. Patients also receive pegylated liposomal doxorubicin hydrochloride IV over 1 hour on day 8. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
After completion of treatment, patients are followed up every 3 months for 2 years, then annually up to 5 years.
3,712 studies on the registry are indexed under Multiple Myeloma; 752 are open to participants now.
This study's enrollment of 31 is below the median of 41 across 2,965 interventional studies indexed under Multiple Myeloma.
Browse Multiple Myeloma studies →University of Washington is the lead sponsor of 1,431 studies on the registry; 226 are open to participants now.
Of its 158 completed or terminated interventional studies of FDA-regulated products, 136 (86%) have results posted.
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Exclusion Criteria:
Patients receive cyclophosphamide IV or PO over 1 hour, bortezomib IV over 3 minutes, and dexamethasone IV or PO on days 1, 8, and 15. Patients also receive pegylated liposomal doxorubicin hydrochloride IV over 1 hour on day 8. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Drug: cyclophosphamide · Drug: pegylated liposomal doxorubicin hydrochloride · Drug: bortezomib · Drug: dexamethasone
Given IV or PO
Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana
Given IV
Also known as: CAELYX, Dox-SL, DOXIL, doxorubicin hydrochloride liposome, LipoDox
Given IV
Also known as: LDP 341, MLN341, VELCADE
Given IV or PO
Also known as: Aeroseb-Dex, Decaderm, Decadron, DM, DXM
Maximum Tolerated Dose of This Combination of Drugs as Assessed by the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (Cohort 1) [MTD Cyclophosphamide, MTD Bortezmib, MTD Docxorubicin]
If 3 patients of cohort 1 require dose reduction of one or more of the medications for toxicity attributed to the drug or drugs, then the starting dose level will be reduced for that drug or drugs for future patients. The initial dosing of drugs for cohort 2 will be permitted to be one dose level above the maximal tolerated doses of cohort 1. Note that this Outcome Measure shows MTD for cyclophosphamide, bortezomib and doxorubicin. MTD for dexamethasone is include in a separate table due to the different Unit of Measure.
Time frame: Up to 90 days after initiation of study treatment
Disease Response Rate (Cohort II)
Disease response using Blade Multiple Myeloma Response Criteria in newly diagnosed (Cohort II) patients who completed at least one cycle of treatment. There were 24 evaluable patients in Cohort II.
Time frame: up to 28 days after last cycle of treatment
Maximum Tolerated Dose of This Combination of Drugs as Assessed by the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (Cohort 1). [Dexamethasone MTD]
If 3 patients of cohort 1 require dose reduction of one or more of the medications for toxicity attributed to the drug or drugs, then the starting dose level will be reduced for that drug or drugs for future patients. The initial dosing of drugs for cohort 2 will be permitted to be one dose level above the maximal tolerated doses of cohort 1. Note that this Outcome Measure will only describe the MTD for dexamethasone. Dexamethasone could not be reported with the MTD for the other three drugs due to a different Unit of Measure.
Time frame: Up to 90 days after initiation of study treatment
| Milestone | Relapsed Disease (Cohort I) | Newly Diagnosed Disease (Cohort II) |
|---|---|---|
| Started | 6 | 25 |
| Completed | 5 | 24 |
| Not completed | 1 | 1 |
If 3 patients of cohort 1 require dose reduction of one or more of the medications for toxicity attributed to the drug or drugs, then the starting dose level will be reduced for that drug or drugs for future patients. The initial dosing of drugs for cohort 2 will be permitted to be one dose level above the maximal tolerated doses of cohort 1. Note that this Outcome Measure shows MTD for cyclophosphamide, bortezomib and doxorubicin. MTD for dexamethasone is include in a separate table due to the different Unit of Measure.
| mg/m2 | Relapsed Disease |
|---|---|
| MTD cyclophosphamide | 300 |
| MTD bortezomib | 1.6 |
| MTD liposomal doxorubicin | 30 |
Disease response using Blade Multiple Myeloma Response Criteria in newly diagnosed (Cohort II) patients who completed at least one cycle of treatment. There were 24 evaluable patients in Cohort II.
| Participants | Newly Diagnosed Patients |
|---|---|
| Complete response (CR) | 2 |
| Near complete response (nCR) | 2 |
| Very good partial response (VGPR) | 3 |
| Partial response (PR) | 11 |
| Stable disease (SD) | 6 |
If 3 patients of cohort 1 require dose reduction of one or more of the medications for toxicity attributed to the drug or drugs, then the starting dose level will be reduced for that drug or drugs for future patients. The initial dosing of drugs for cohort 2 will be permitted to be one dose level above the maximal tolerated doses of cohort 1. Note that this Outcome Measure will only describe the MTD for dexamethasone. Dexamethasone could not be reported with the MTD for the other three drugs due to a different Unit of Measure.
| mg | Relapsed Disease (Cohort I) |
|---|---|
| Maximum Tolerated Dose of This Combination of Drugs as Assessed by the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (Cohort 1). [Dexamethasone MTD] | 40 |
Collected over Through 45 days after the last dose of study drug.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Treatment (Chemotherapy and Enzyme Inhibitor) | — | 1/31 (3.2%) | 31/31 (100%) |
| Event | Treatment (Chemotherapy and Enzyme Inhibitor) |
|---|---|
| Thromboembolic eventVascular disorders | 1/31 |
| Event | Treatment (Chemotherapy and Enzyme Inhibitor) |
|---|---|
| FatigueGeneral disorders | 18/31 |
| NauseaGastrointestinal disorders | 10/31 |
| ConstipationGastrointestinal disorders | 10/31 |
| AnemiaBlood and lymphatic system disorders | 8/31 |
| Peripheral neuropathyNervous system disorders | 7/31 |
| HypoalbuminemiaInvestigations | 5/31 |
| NeutropeniaInvestigations | 5/31 |
| Hand foot and mouth diseaseInfections and infestations | 4/31 |
| LeukopeniaInvestigations | 4/31 |
| InsomniaPsychiatric disorders | 3/31 |
| Age, Categorical(Participants) | Treatment (Chemotherapy and Enzyme Inhibitor) |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 25 |
| >=65 years | 6 |
| Sex: Female, Male(Participants) | Treatment (Chemotherapy and Enzyme Inhibitor) |
|---|---|
| Female | 17 |
| Male | 14 |
| Ethnicity (NIH/OMB)(Participants) | Treatment (Chemotherapy and Enzyme Inhibitor) |
|---|---|
| Hispanic or Latino | 2 |
| Not Hispanic or Latino | 24 |
| Unknown or Not Reported | 5 |
| Race (NIH/OMB)(Participants) | Treatment (Chemotherapy and Enzyme Inhibitor) |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 1 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 1 |
| White | 29 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
This study is terminated, as verified in Aug 2017. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Cyclophosphamide · Liposomal doxorubicin · Bortezomib · Dexamethasone