A Study Of Daratumumab, Low-Dose Oral Dexamethasone and Cyclophosphamide With Or Without Pomalidomide

Phase 2

Completed

• Conditions: Multiple Myeloma
• Interventions: Biological: DCdP; Biological: DCd+P

• Registration Number: NCT03215524
• Lead Sponsor: Canadian Myeloma Research Group

Brief Summary

This is a randomized phase II open label study of daratumumab, weekly low-dose oral cyclophosphamide and dexamethasone with or without pomalidomide in patients with relapsed and refractory multiple myeloma. The study consists of two arms. Patients will be randomized into ARM A and ARM B in a 1:1 ratio.

Detailed Description

This is a randomized phase II open label study of daratumumab, weekly low-dose oral cyclophosphamide and dexamethasone with or without pomalidomide in patients with relapsed and refractory multiple myeloma. The study consists of two arms. Patients will be randomized into ARM A and ARM B in a 1:1 ratio.

In treatment ARM A patients will receive daratumumab, cyclophosphamide, dexamethasone and pomalidomide as per the following schedule:

* Daratumumab, IV, at 16 mg/kg, or Daratumumab, SC, at 1800 mg on days 1, 8, 15 and 22 for Cycles 1 and 2, on Days 1 and 15 for Cycles 3-6, and Day 1 of each cycle for Cycle 7 and beyond for each 28-day cycle.

* Cyclophosphamide, orally, at 400 mg on Days 1, 8, 15 of each 28-day cycle. In order to prevent myelotoxicity and bladder toxicity, cyclophosphamide will be discontinued after cycle 24.

* Dexamethasone orally at 20 mg on day of daratumumab administration (pre-daratumumab) and 20 mg on the following day. On weeks without daratumumab administration, 40 mg dexamethasone weekly.

* Pomalidomide, orally, at 4 mg on Days 1- 21 of each 28-day cycle.

In treatment ARM B, patients will receive daratumumab, cyclophosphamide, dexamethasone and pomalidomide as per the following schedule:

* Daratumumab, IV, at 16 mg/kg, or Daratumumab, SC, at 1800 mg on days 1, 8, 15 and 22 for Cycles 1 and 2, on Days 1 and 15 for Cycles 3-6, and Day 1 of each cycle for Cycle 7 and beyond for each 28-day cycle.

* Cyclophosphamide, orally, at 400 mg on Days 1, 8 and 15 of each 28-day cycle. In order to prevent myelotoxicity and bladder toxicity, cyclophosphamide will be discontinued after cycle 24.

* Dexamethasone at 20 mg orally on day of daratumumab administration (pre-daratumumab) and 20 mg on the following day. On weeks without daratumumab administration, 40mg dexamethasone weekly.

* Pomalidomide, orally, added at first progression at 4 mg on Days 1- 21 of each 28-day cycle.

Individual subjects will remain on treatment as long as there is no evidence of disease progression or unacceptable toxicity or patient/physician decision to discontinue. Disease assessment as determined by the Site Investigator will be made according to the IMWG response criteria guidelines for MM.

Study Timeline

• Study First Submitted: 2017-06-05
• Study First Submitted QC: 2017-07-11
• Study First Posted: 2017-07-12
• Study Start: 2017-10-25
• Primary Completion: 2022-06-24
• Study Completion: 2022-06-24
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-03
• Last Update Posted: 2023-08-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ARM A	DCdP	Daratumumab, Cyclophosphamide, Dexamethasone, Pomalidomide Daratumumab, IV, at 16 mg/kg, or Daratumumab, SC, at 1800 mg on days 1, 8, 15 and 22 for Cycles 1 and 2, on Days 1 and 15 for Cycles 3-6, and Day 1 of each cycle for Cycle 7 and beyond for each 28-day cycle. Cyclophosphamide, orally, at 400 mg on Days 1, 8, 15 of each 28-day cycle for 24 cycles. Dexamethasone, orally, at 20 mg on day of daratumumab administration (pre-daratumumab) and 20 mg on the following day. On weeks without daratumumab administration, 40 mg dexamethasone weekly. Pomalidomide, orally, at 4 mg on Days 1- 21 of each 28-day cycle.
ARM B	DCd+P	Daratumumab, Cyclophosphamide, Dexamethasone, Pomalidomide Daratumumab, IV, at 16 mg/kg, or Daratumumab, SC, at 1800 mg on days 1, 8, 15 and 22 for Cycles 1 and 2, on Days 1 and 15 for Cycles 3-6, and Day 1 of each cycle for Cycle 7 and beyond for each 28-day cycle. Cyclophosphamide, orally, at 400 mg on Days 1, 8 and 15 of each 28-day cycle for 24 cycles. Dexamethasone,orally, at 20 mg on day of daratumumab administration (pre-daratumumab) and 20 mg on the following day. On weeks without daratumumab administration,40mg dexamethasone weekly. Pomalidomide, orally, added at first progression at 4 mg on Days 1- 21 of each 28-day cycle.

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival	36 months of from randomization	Progression-free survival evaluation after 36 months

Trial Locations

Locations (11)

CancerCare Manitoba; 🇨🇦 Winnipeg, Manitoba, Canada

CrossCancer Institute; 🇨🇦 Edmonton, Alberta, Canada

Thunder Bay Regional Health Sciences Centre; 🇨🇦 Thunder Bay, Ontario, Canada

Saskatoon Cancer Centre; 🇨🇦 Saskatoon, Saskatchewan, Canada

Tom Baker Cancer Centre; 🇨🇦 Calgary, Alberta, Canada

The Ottawa Hospital; 🇨🇦 Ottawa, Ontario, Canada

Princess Margaret Cancer Centre; 🇨🇦 Toronto, Ontario, Canada

Juravinski Cancer Centre (Hamilton Health Sciences Centre); 🇨🇦 Hamilton, Ontario, Canada

Fraser Valley Cancer Centre; 🇨🇦 Surrey, British Columbia, Canada

QEII Health Sciences Centre; 🇨🇦 Halifax, Nova Scotia, Canada

Saint John Regional Hospital; 🇨🇦 Saint John, New Brunswick, Canada