Pomalidomide, Ixazomib, and Dexamethasone With or Without Intensification by Cyclophosphamide in Relapsed or Refractory Multiple Myeloma

NCT03731832 | Completed Phase 2

• 1 other identifier: DSMM XV
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 11

Brief Summary

The study is designed as a multicenter, non-randomized, Phase II trial with one treatment arm. A total of 82 patients of both genders and older than 18 years with relapsed/refractory multiple myeloma are planned to be included in the study. After the first 6 patients will have finished the first treatment cycle of the induction phase the DMC will assess safety and tolerability of the treatment schedule and decide about the further continuation of the study.

Conditions

Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Overall Response rate (PId) according to the IMWG criteria.

  Overall response rate at PId

  1 year throughout study completion

Secondary Outcomes (6)

• Disease control rate

  1 year throughout study completion

• Overall response rate

  1 year throughout study completion

• Disease control rate in patients intensified with PICd (at least SD)

  1 year throughout study completion

• Progression-free survival (PFS)

  1 year throughout study completion

• Overall survival (OS)

  1 year throughout study completion

Other Outcomes (2)

• Molecular cytogenetics by FISH analysis

  1 year throughout study completion

• Safety of the dosing regimens and relationship of AEs

  1 year throughout study completion

Study Arms (2)

PId

EXPERIMENTAL

Treatment of eligible patients with combination of Pomalidomide, Ixazomib, Dexamethasone for all patients until disease progression.

Drug: MLN9708; Drug: Pomalidomide 4 MG Oral Capsule; Drug: Dexamethasone

PICd

EXPERIMENTAL

Treatment of patients showing an isolated biochemical relapse at disease progression with combination of Pomalidomide, Ixazomib, Dexamethasone plus Cyclophosphamide.

Drug: MLN9708; Drug: Pomalidomide 4 MG Oral Capsule; Drug: Dexamethasone; Drug: Cyclophosphamide

Interventions

MLN9708 DRUG

Study drug will be given as a single, oral dose of 4.0 mg weekly (day 1, 8 and 15) for 3 weeks, followed by 1 week without study drug in a 28-day cycle

Also known as: Ixazomib 4.0 mg

PICd; PId

Pomalidomide 4 MG Oral Capsule DRUG

Study drug will be given as an oral dose of 4.0 mg on day 1 until day 21, followed by 1 week without study drug in a 28-day cycle.

PICd; PId

Dexamethasone DRUG

Dexamethasone will be administered as a single, oral dose of 40 mg/day weekly on day 1, 8, 15 and 22 in patients from 18 to 74 years old. For patients ≥ 75 years old dose has to be reduced to 20 mg/day with the same treatment schedule.

PICd; PId

Cyclophosphamide DRUG

Cyclophosphamide will be administered once daily as an oral dose of 50 mg on cycle days 1 to 21, followed by one week without drug in a 28-day cycle.

PICd

Eligibility Criteria

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

You may qualify if:

• Male or female patients ≥ 18 years of age at the time of signing the informed consent form
• Patients capable to understand the purposes and risks of the study, who are willing and able to participate in the study and from whom written and dated informed consent to participate in the study has been obtained prior to any study related assessments/ procedures being conducted
• Patients with relapsed or refractory, histologically confirmed multiple myeloma
• Patients must have received at least two but not more than four prior anti-myeloma regimens including lenalidomide and bortezomib and have demonstrated disease progression on the last therapy
• Prior treatments must have included both lenalidomide and bortezomib: at least two consecutive cycles of lenalidomide and bortezomib (alone or in combination) and adequate prior alkylator exposure. This is either as part of a stem cell transplant or at least 6 consecutive cycles of an alkylator-based therapy.
• Patients must have failed bortezomib and lenalidomide therapy: progression within 60 days; PR or better with progression within 6 month and/or bortezomib intolerant after ≥ 2 cycles and achieving ≤ MR
• Relapsed from or refractory to at least one regimen (induction, autologous stem cell transplantation (or allogenic stem cell transplantation) and consolidation/maintenance are considered one "regimen")
• Measurable levels of serum and/or urine M-protein: serum M-protein ≥ 5 g/L and/or urine M-protein ≥ 200 mg/24h or serum free light chain (sFLC) concentration of \> 100 mg/L of the involved FLC, provided sFLC ratio is abnormal (sFLC K/λ ratio (\< 0.26 or \> 1.65)
• Life expectancy ≥ 3 months
• ECOG performance status of 0, 1, or 2
• Patients must be able to adhere to the study visit schedule and other protocol requirements
• All women and men must acknowledge to have understood the hazards and necessary precautions associated with the use of pomalidomide and ixazomib
• All subjects must agree in writing to strictly adhere to the Pomalidomide Pregnancy Prevention Plan as given in Appendix C
• Females of childbearing potential (FCBP) must:
• Understand the potential teratogenic risk to the unborn child

You may not qualify if:

• Concomitant cancer chemo- or radiotherapy (except for local radiation therapy for preexisting lytic lesions)
• Treatment with any investigational product within 60 days prior to first administration of pomalidomide and ixazomib
• Patients eligible for autologous and / or allogeneic stem cell transplantation
• Abnormal/inadequate organ or bone marrow function as defined below (any single parameter to fulfill condition): ANC \< 1 x 109/L
• Hemoglobin \< 8.0 g/dL (prior RBC transfusion or recombinant human erythropoietin use is permitted)
• Platelet count \< 75 x 109/L for patients in whom \< 50% of bone marrow nucleated cells are plasma cells
• Platelet count \< 30 x 109/L for patients in whom ≥ 50% of bone marrow nucleated cells are plasma cells
• Estimated GFR (MDRD) \< 45 ml/min
• AST/ALT \> 3 x upper limit of normal (ULN)
• Serum (total) bilirubin \> 1.5 x ULN
• Corrected serum calcium \> 14 mg/dL (\> 3.5 mmol/L); or free ionized calcium \> 6.5 mg/dL (\> 1.6 mmol/L)
• Serum creatinine \> 1.5 x ULN
• Prior pomalidomide based therapy
• Prior ixazomib based therapy
• Baseline peripheral neuropathy \> Grade 1 on clinical examination within 14 days before enrollment

Sponsors & Collaborators

• GWT-TUD GmbH: lead

Study Sites (11)

Klinikum rechts der Isar der TU München / III. Med. Klinik und Poliklinik

Munich, Bavaria, 81675, Germany

Location

phase drei Hämato-Onkologischer Studienkreis am Klinikum Aschaffenburg

Aschaffenburg, 63739, Germany

Location

Sozialstiftung Bamberg / Klinik am Bruderwald, Zentrum für Innere Medizin, Med. Klinik V, Hämatologie und internistische Onkologie

Bamberg, 96049, Germany

Location

Klinikum der Johann Wolfgang Goethe-Universität Frankfurt am Main

Frankfurt am Main, 60590, Germany

Location

Universitätsklinikum Jena / Klinik für Innere Medizin II, Abteilung für Hämatologie und internistische Onkologie

Jena, 07747, Germany

Location

Universitätsklinikum Magdeburg A.Ö.R / Klinik für Hämatologie und Onkologie

Magdeburg, 39120, Germany

Location

Kliniken Ostalb Stauferklinikum Schwäbisch Gmünd

Mutlangen, 73557, Germany

Location

Universitätsklinikum Münster / Medizinische Klinik A

Münster, 48149, Germany

Location

Studienzentrum Onkologie Ravensburg

Ravensburg, 88212, Germany

Location

Universitätsklinikum Ulm / Klinik für Innere Medizin III

Ulm, 89081, Germany

Location

Universitätsklinikum Würzburg

Würzburg, 97080, Germany

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

ixazomib; pomalidomide; Dexamethasone; Cyclophosphamide

Condition Hierarchy (Ancestors)

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 Officials

• Stefan Knop, Prof.

  Universitätsklinikum Würzburg / Medizinische Klinik und Poliklinik II

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: All patients receive PId. Patients showing a biochemical relapse receive PICd afterwards, while patients showing a clinical relapse go off study.

Study Record Dates

• First Submitted: October 1, 2018
• First Posted: November 6, 2018
• Study Start: September 20, 2018
• Primary Completion: April 22, 2024
• Study Completion: April 22, 2024
• Last Updated: September 30, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

DE (11)