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

NCT03215524 | Completed Phase 2 DMC

• 1 other identifier: CMRG 004
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 11

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.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival

  Progression-free survival evaluation after 36 months

  36 months of from randomization

Study Arms (2)

ARM A

EXPERIMENTAL

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.

Biological: DCdP

ARM B

EXPERIMENTAL

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.

Biological: DCd+P

Interventions

DCd+P BIOLOGICAL

Daratumumab, Cyclophosphamide, Dexamethasone, + Pomalidomide added only at first confirmed biochemical progression

Also known as: Darzalex, Cytoxan, Pomalyst, Daratumumab, Cyclophosphamide, Dexamethasone

ARM B

Eligibility Criteria

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

You may qualify if:

• Males or females, age 18 years or older.
• ECOG performance status score of 0, 1 or 2.
• Life expectancy of at least 3 months.
• Measurable disease according to the IMWG criteria defined below. (These baseline laboratory studies for determining eligibility must be obtained during the screening period within 28 days prior to start of study drug):
• Serum monoclonal paraprotein (M-protein) ≥ 10 g/L (if IgG) or ≥5g/L (if IgA, D, E or M)
• Urine M-protein ≥ 200 mg/24 h
• Serum free light chains (FLC) assay: Involved FLC level ≥ 100 mg/L and an abnormal serum free light chain ratio (\< 0.26 or \> 1.65).
• Relapsed or relapsed and refractory disease defined as documented disease progression during or after completing their last treatment line and it must have contained either a proteasome inhibitor and/or lenalidomide. The only exception for non-refractory patients is when re-treatment with these agents is medically contra-indicated.
• Have undergone at least 1 prior line of therapy. Induction therapy followed by ASCT and consolidation/maintenance will be considered as one line.
• Have achieved at least a Minimal Response (MR) or better to at least one previous line of therapy, as per IMWG response criteria.
• Have received at least 2 consecutive cycles of prior treatment that have included lenalidomide or a proteasome inhibitor, either alone or in combination regimens, unless intolerant to these agents.
• Subjects must be eligible for pomalidomide reimbursement by their provincial jurisdictions or by the criteria of their insurance companies.
• The following laboratory results must be met within 10 days of first study drug adminitration:
• ANC ≥ 1.0 x 109/L
• Hemoglobin ≥ 80 g/L

You may not qualify if:

• Prior exposure to daratumumab (or other anti-CD38 monoclonal antibody) or pomalidomide.
• History of prior allogeneic stem cell transplantation and showing evidence of active graft-versus-host disease or graft-versus-host disease that requires immunosuppressive therapy.
• Chemotherapy or other anti-myeloma therapy within 14 days prior to the first dose of study drug.
• Treatment-related toxicity that has not recovered ≤Grade 1 unless deemed to be irreversible (an example of an irreversible toxicity would include steroid induced cataracts). Peripheral neuropathy \> Grade 2 or Grade 2 with pain will be excluded.
• Subjects who have received steroids within 2 weeks prior to starting study treatment or who have not recovered from side effects of such therapy. Concomitant therapy medications that include corticosteroids are allowed if subject receive ≤ 10 mg of prednisone per day, or equivalent, as indicated for other medical conditions, or up to 100 mg of hydrocortisone as pre-medication for administration of certain medications or blood products prior to enrollment in this study.
• Subjects who have received any investigational agents within 28 days or 5 half-lives (whichever is shorter, however the minimum allowed timeframe is 14 days) of the first dose (Cycle 1, Day 1).
• Prior history of malignancies, other than MM, unless the subject has been free of the disease for 3 years or longer. Exceptions include the following:
• Basal or squamous cell carcinoma of the skin,
• Carcinoma in situ of the cervix or breast,
• Adenocarcinoma of the prostate (TNM stage of T1a or T1b).
• Other concurrent severe and/or uncontrolled medical conditions (i.e. uncontrolled diabetes, active or uncontrolled infection, acute diffuse pulmonary disease, pericardial disease, uncontrolled thyroid dysfunction) including abnormal laboratory values, that could cause unacceptable safety risks or compromise compliance with the protocol.
• Known chronic obstructive pulmonary disease (COPD), defined as a FEV1 \<50% predicted.
• Known moderate or severe persistent asthma within the last 2 years, or currently has uncontrolled asthma of any classification.
• History of or current uncontrolled cardiovascular disease including:
• Unstable angina, myocardial infarction, or known congestive heart failure Class III/IV (Appendix 5) within the preceding 12 months.

Sponsors & Collaborators

• Canadian Myeloma Research Group: lead

Study Sites (11)

Tom Baker Cancer Centre

Calgary, Alberta, Canada

Location

CrossCancer Institute

Edmonton, Alberta, Canada

Location

Fraser Valley Cancer Centre

Surrey, British Columbia, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, Canada

Location

Saint John Regional Hospital

Saint John, New Brunswick, Canada

Location

QEII Health Sciences Centre

Halifax, Nova Scotia, Canada

Location

Juravinski Cancer Centre (Hamilton Health Sciences Centre)

Hamilton, Ontario, Canada

Location

The Ottawa Hospital

Ottawa, Ontario, Canada

Location

Thunder Bay Regional Health Sciences Centre

Thunder Bay, Ontario, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Location

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, Canada

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

2'-deoxycytidine diphosphate; daratumumab; Cyclophosphamide; pomalidomide; Dexamethasone

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)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Design

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

Study Record Dates

• First Submitted: June 5, 2017
• First Posted: July 12, 2017
• Study Start: October 25, 2017
• Primary Completion: June 24, 2022
• Study Completion: June 24, 2022
• Last Updated: August 4, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (11)