Pomalidomide/Cyclophosphamide/Dexamethasone in Relapse Refractory Myeloma: Safety Profile in Mexicans

NCT ID: NCT03601624

Last Updated: 2018-11-14

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-01
• Study Completion Date: 2020-07-30

Brief Summary

Despite available therapies, MM uniformly fatal and participants who have received prior lenalidomide (Len) and bortezomib have a median overall survival (OS) of 9 months.

Pomalidomide (Pom) plus low-dose dexamethasone (Dex) significantly improved efficacy parameters in terms of progression free survival (PFS), OS, and overall response (ORR) compared with high-dose Dex in participants with refractory or relapsed, and refractory MM, including participants with disease refractory to both bortezomib and lenalidomide.

Alkylating agents also represent standard therapies for participants with MM. There are some reports demonstrating combination of Len and continuous cyclophosphamide (Cy) achieve an ORR of 50% in Len refractory participants, suggesting Cy may be able to overcome resistance to Len.

The investigators aimed to assess the safety in Mexican MM participants in relapse/refractory stage of the triple combination: IV Cy in combination with Pom plus Dex until disease progression. A multicenter study is proposed.

Primary endpoint: Safety. Efficacy as secondary endpoint: PF, OS and ORR.

Detailed Description

Multiple myeloma is a plasma cell malignancy with accounts for about 1% of all cancers. Despite available therapies, the disease remains uniformly fatal and participants who have received prior lenalidomide and bortezomib have a median overall survival of 9 months.

Combination therapy is often used in clinical practice. In an attempt to overcome drug/clone resistance, other report with pomalidomide, dexamethasone and cyclophosphamide (PomCyDex) show efficacy and safety information, regimen for refractory myeloma patients with higher overall response rate than pomalidomide and dexamethasone.

In this case a phase II trial scheme is proposed: 1. Pomalidomide at 4 mg orally on days 1-21 of a 28 day cycle, 2. Cyclophosphamide 300 mg IV on days 1 and 15 of a 28 day cycle; and 3. Dexamethasone 40 mg PO weekly. Participants who were >75 years of age or those who were known to be intolerant to 40 mg weekly dexamethasone are going to receive 20 mg dexamethasone on the same schedule.

Pomalidomide is a drug wide studied in American and European population, but not in México. Even it has been approved by local Regulatory authority, there is not any trial supporting data about safety and efficacy in Mexican population. Alkylating agents are very active in MM, and in combination with novel therapies, such as immunomodulatory drugs, has shown to enhance efficacy in relapsed/refractory setting.

It is proposed phase 2 study to assess safety and efficacy of treatment with Pomalidomide in combination with Cyclophosphamide and dexamethasone in a sample of Mexican RRMM participants from ISSSTE.

Conditions

Multiple Myeloma in Relapse; Multiple Myeloma Progression; Refractory Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental

1. Pomalidomide at 4 mg orally on days 1-21 of a 28 day cycle

2. Cyclophosphamide 300 mg IV on days 1 and 15 of a 28 day cycle.

3. Dexamethasone 40 mg PO weekly.(Or 20 mg if patients are older than 75 years )

Group Type: EXPERIMENTAL

Pomalidomide

Intervention Type: DRUG

1. Pomalidomide at 4 mg orally on days 1-21 of a 28 day cycle

2. Cyclophosphamide 300 mg IV on days 1 and 15 of a 28 day cycle.

3. Dexamethasone 40 mg PO weekly.(Or 20 mg if patients are older than 75 years )

Interventions

Pomalidomide

1. Pomalidomide at 4 mg orally on days 1-21 of a 28 day cycle

2. Cyclophosphamide 300 mg IV on days 1 and 15 of a 28 day cycle.

3. Dexamethasone 40 mg PO weekly.(Or 20 mg if patients are older than 75 years )

Intervention Type: DRUG

Other Intervention Names

Cyclophosphamide; Dexamethasone

Eligibility Criteria

Inclusion Criteria

1. 18 years old

2. Relapsed and refractory multiple myeloma patients that had received ≥2 prior lines of therapies including a proteasome inhibitor and Lenalidomide; if cyclophosphamide was included in a previous line, complete scheme has to be finished at least 6 months previously to initiate in this IIT.

3. Measurable disease as defined by the presence of 1 of the following: serum monoclonal protein ≥0.5 g/dL; urine monoclonal protein >200 mg/24 h; or serum involved free light chain ≥10 mg/dL and abnormal serum free light chain ratio.

4. ECOG 0 to 2

5. Serum creatinine level <3mg/dL.

6. Absolute neutrophil count ≥1000/mm3, and a platelet count ≥30 000/mm3.

7. Females of childbearing potential has to have a negative serum or urine pregnancy test within 10 to 14 days prior to, and within 24 hours of, starting pomalidomide.

8. A washout period of 2 weeks prior to cycle 1 day 1 from prior therapies are required.

Exclusion Criteria

1. Patients with known hypersensitivity to thalidomide or lenalidomide

2. Patients who had HIV or active hepatitis B or C;

3. Patients with grade 3 or more neuropathy

4. Patients with active malignancy requiring therapy within the next year.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado

OTHER_GOV

Sponsor Role: lead

Responsible Party

Martha Alvarado Ibarra

Chief of Hematology Area

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

MARTHA ALVARADO, MD

Role: PRINCIPAL_INVESTIGATOR

Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado

Locations

ISSSTE

Mexico City, , Mexico

Site Status: RECRUITING

Countries

Mexico

Central Contacts

MARTHA A ALVARADO, MD

Role: CONTACT

normoblasto@gmail.com

0445525600960

JOSE LUIS ALVAREZ, MD

Role: CONTACT

draselo@hotmail.com

55525532257383

Facility Contacts

MARTHA A ALVARADO, MD

Role: primary

normoblasto@gmail.com

15525600960

References

Richardson PG, Mark TM, Lacy MQ. Pomalidomide: new immunomodulatory agent with potent antiproliferative effects. Crit Rev Oncol Hematol. 2013 Oct;88 Suppl 1:S36-44. doi: 10.1016/j.critrevonc.2013.02.001. Epub 2013 Jun 17.

Reference Type: BACKGROUND

PMID: 23786844 (View on PubMed)

Miguel JS, Weisel K, Moreau P, Lacy M, Song K, Delforge M, Karlin L, Goldschmidt H, Banos A, Oriol A, Alegre A, Chen C, Cavo M, Garderet L, Ivanova V, Martinez-Lopez J, Belch A, Palumbo A, Schey S, Sonneveld P, Yu X, Sternas L, Jacques C, Zaki M, Dimopoulos M. Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013 Oct;14(11):1055-1066. doi: 10.1016/S1470-2045(13)70380-2. Epub 2013 Sep 3.

Reference Type: BACKGROUND

PMID: 24007748 (View on PubMed)

Dimopoulos MA, Leleu X, Palumbo A, Moreau P, Delforge M, Cavo M, Ludwig H, Morgan GJ, Davies FE, Sonneveld P, Schey SA, Zweegman S, Hansson M, Weisel K, Mateos MV, Facon T, Miguel JF. Expert panel consensus statement on the optimal use of pomalidomide in relapsed and refractory multiple myeloma. Leukemia. 2014 Aug;28(8):1573-85. doi: 10.1038/leu.2014.60. Epub 2014 Feb 5.

Reference Type: BACKGROUND

PMID: 24496300 (View on PubMed)

Baz RC, Martin TG 3rd, Lin HY, Zhao X, Shain KH, Cho HJ, Wolf JL, Mahindra A, Chari A, Sullivan DM, Nardelli LA, Lau K, Alsina M, Jagannath S. Randomized multicenter phase 2 study of pomalidomide, cyclophosphamide, and dexamethasone in relapsed refractory myeloma. Blood. 2016 May 26;127(21):2561-8. doi: 10.1182/blood-2015-11-682518. Epub 2016 Mar 1.

Reference Type: BACKGROUND

PMID: 26932802 (View on PubMed)

Martha Alvarado Ibarra, Manuel López Hernández, José LuisAlvarez Vera, Maricela Ortiz Zepeda, Verónica Mena Zepeda and Eugenia Espitia Ríos. Outcomes and Evolution In The Tratment Of Multiple Myeloma In The Last 20 Years Experience Of A Mexican Institution. International Journal of Information Research and Review 3(9):2811-2817, 2016

Reference Type: BACKGROUND

Other Identifiers

ISSSTE-POM-CY-MM-2018

Identifier Type: -

Identifier Source: org_study_id