ANCHOR: Study of Melphalan Flufenamide (Melflufen) + Dex With Bortezomib or Daratumumab in Patients With RRMM

• Sponsor: Oncopeptides AB (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03481556
• Collaborator: (none)
• Enrollment: 56
• Locations: 16
• Arms: 2
• Actual Duration (Months): 45.6
• Patients Per Site: 3.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is an open-label Phase 1/2a study which will enroll patients that have relapsed or relapsed-refractory multiple myeloma following 1-4 lines of prior therapy. Patients will receive either melflufen+dexamethasone+bortezomib or melflufen+dexamethasone+daratumumab and are required to be IMiD refractory to be enrolled to the bortezomib regimen, and to not have any prior exposure to daratumumab or other antiCD-38 mAb to be enrolled to the daratumumab regimen.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Melphalan flufenamide (Melflufen); Drug: Dexamethasone; Drug: Bortezomib; Drug: Daratumumab	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 56 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label Phase 1/2a Study of the Safety and Efficacy of Melflufen and Dexamethasone in Combination With Either Bortezomib or Daratumumab in Patients With Relapsed or Relapsed-Refractory Multiple Myeloma
• Actual Study Start Date: Apr 16, 2018
• Actual Primary Completion Date: Feb 2, 2022
• Actual Study Completion Date: Feb 2, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A (melflufen+bortezomib+dex) Melflufen 30 mg and 40 mg or 20 mg i.v. Day 1 of each 28-day cycle in combination with bortezomib at 1.3mg/m² S.Q. on Days 1, 4, 8, 11 and dexamethasone 20 mg (12 mg ≥ 75 years) Days 1, 4, 8, 11 and 40 mg (20 mg ≥ 75 years) on Day 15 and 22 of each 28-day cycle.	Drug: Melphalan flufenamide (Melflufen); Intravenous infusion; Drug: Dexamethasone; Oral tablets; Other Names: Dex Fortecortin Decadron ; Drug: Bortezomib; Subcutaneous administration; Other Names: Velcade
Experimental: B (melflufen+daratumumab+dex) Melflufen 30 mg and 40 mg or 20 mg i.v. Day 1 of each 28-day cycle in combination with daratumumab 16 mg/kg weekly for 8 doses, every other week for 8 doses and then once every 4 weeks. Dexamethasone p.o. 40 mg weekly (20 mg weekly for patients age ≥ 75 years).	Drug: Melphalan flufenamide (Melflufen); Intravenous infusion; Drug: Dexamethasone; Oral tablets; Other Names: Dex Fortecortin Decadron ; Drug: Daratumumab; Intravenous infusion; Other Names: Dara Darzalex

Outcome Measures

Primary Outcome Measures

1. Phase 1: The primary endpoint of Phase 1 is to monitor and analyze the frequency and grade of AEs occurring during Cycle 1 at each dose level to be tested. Each Regimen to be evaluated separately. [During first cycle (28 days) of each cohort]

   Dose-limiting toxicity to determine the optimal dose of melflufen, up to a maximum of 40 mg, given every 28 days in triple drug combination therapy

2. Phase 2: Overall Response Rate (ORR) [zFrom start of treatment until best response achieved before confirmed progression. For an average patient this is achieved within 6 months.]

   To evaluate overall response rate according to IMWG, including CR, VGPR and PR.

Secondary Outcome Measures

1. The proportion of efficacy evaluable patients in each Regimen who achieve a confirmed sCR, CR, VGPR, or PR as their best response. Each Regimen to be evaluated separately. [From start of treatment until best response achieved before confirmed progression. For an average patient this is achieved within 6 months.]

   Investigators assessment of response according to IMWG criteria

2. Duration of Response (DOR) [From first evidence of response until confirmed progression, to be assessed up to 24 months]

   To assess the DOR

3. Time to Response (TTR) [From start of dosing until time of response. For an average patient this is achieved within 6 months.]

   To assess the TTR

4. Progression-Free Survival (PFS) [From start of dosing until confirmed progression, to be assessed up to 24 months]

   To assess the PFS

5. Overall Survival (OS) [From start of dosing until end of study (2 years after confirmed progression)]

   To assess the OS data

6. Frequency and Grade of Adverse Events [From start of dosing until 30 days after last dose, to be assessed up to 24 months]

   To assess the safety and tolerability through AE reporting following CTCAE v4

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Male or female, age 18 years or older

2. A prior diagnosis of multiple myeloma with documented disease progression in need of treatment at time of screening

3. One to four prior lines of therapy

4. Measurable disease defined as any of the following:

• Serum monoclonal protein ≥ 0.5 g/dL by serum protein electrophoresis (SPEP)

• ≥ 200 mg/24 hours of monoclonal protein in the urine on 24-hour urine electrophoresis (UPEP)

• Serum free light chain (SFLC) ≥ 10 mg/dL AND abnormal serum kappa to lambda free light chain ratio

1. Life expectancy of ≥ 6 months

2. ECOG performance status ≤ 2. (Patients with lower performance status based solely on bone pain secondary to multiple myeloma may be eligible following consultation and approval of the medical monitor)

3. Patient is a female of childbearing potential (FCBP)* with a negative serum or urine pregnancy test prior to initiation of therapy and agrees to practice appropriate methods of birth control, or the patient is male and agrees to practice appropriate methods of birth control

4. Ability to understand the purpose and risks of the study and provide signed and dated informed consent

5. 12-lead Electrocardiogram (ECG) with QT interval calculated by Fridericia Formula (QTcF) interval of ≤ 470 msec

6. Adequate organ function with the following laboratory results during screening (within 21 days) and immediately before study drug administration on Cycle 1 Day 1:

• Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3 (1.0 x 109/L) (Growth factors cannot be used within 10 days (14 days for pegfilgrastim) prior to initiation of therapy)

• Platelet count ≥ 75,000 cells/mm3 (75 x 109/L) (without required transfusions during the 10 days prior to initiation of therapy)

• Hemoglobin ≥ 8.0 g/dl (red blood cell (RBC) transfusions are permitted)

• Total Bilirubin ≤ 1.5 x upper limit of normal (ULN), or patients diagnosed with Gilbert's syndrome, that have been reviewed and approved by the medical monitor

• AST/SGOT and ALT/SGPT ≤ 3.0 x ULN

• Renal function: Estimated creatinine clearance by Cockcroft-Gault formula ≥ 45 mL/min and serum creatinine ≤ 2 mg/dL

1. Must have, or be willing to have an acceptable central catheter. (Port a cath, peripherally inserted central catheter [PICC] line, or central venous catheter)

• (FCBP) is any sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally postmenopausal (not having menstrual cycles due to cancer therapy does not rule out childbearing potential) for at least 24 consecutive months.

Exclusion Criteria:

1. Primary refractory disease (i.e. never responded with ≥ MR to any prior therapy)

2. Evidence of mucosal or internal bleeding and/or are platelet transfusion refractory (i.e. platelet count fails to increase by > 10,000 cells/mm3 after transfusion of an appropriate dose of platelets)

3. Any medical conditions that, in the Investigator's opinion, would impose excessive risk to the patient or would adversely affect his/her participating in this study. Examples of such conditions are: a significant history of cardiovascular disease (e.g., myocardial infarction, significant conduction system abnormalities, uncontrolled hypertension, ≥ Grade 3 thromboembolic event in the last 6 months)

4. Known active infection requiring parenteral or oral anti-infective treatment within 14 days of initiation of therapy

5. Other malignancy diagnosed or requiring treatment within the past 3 years with the exception of adequately treated basal cell carcinoma, squamous cell skin cancer, carcinoma in-situ of the cervix or breast or very low and low risk prostate cancer in active surveillance

6. Pregnant or breast-feeding females

7. Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse compliance or follow-up evaluation

8. Known human immunodeficiency virus or active hepatitis B or C viral infection

9. Concurrent symptomatic amyloidosis or plasma cell leukemia

10. POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes)

11. Previous cytotoxic therapies, including cytotoxic investigational agents, for multiple myeloma within 3 weeks (6 weeks for nitrosoureas) prior to initiation of therapy. The use of live vaccines within 30 days before initiation of therapy. IMiDs, PIs and or corticosteroids within 2 weeks prior to initiation of therapy. Other investigational therapies and monoclonal antibodies (mAb) within 4 weeks of initiation of therapy Prednisone up to but no more than 10 mg orally once daily (q.d.) or its equivalent for symptom management of comorbid conditions is permitted but dose should be stable for at least 7 days prior to initiation of therapy

12. Residual side effects to previous therapy > Grade 1 prior to initiation of therapy (Alopecia any grade and/or neuropathy Grade 1 without pain are permitted)

13. Prior peripheral stem cell transplant within 12 weeks of initiation of therapy

14. Prior allogeneic stem cell transplantation with active graft-versus-host- disease

15. Prior major surgical procedure or radiation therapy within 4 weeks of initiation of therapy (this does not include limited course of radiation used for management of bone pain within 7 days of initiation of therapy)

16. Known intolerance to the required dose and schedule of steroid therapy as determined by the investigator

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
2	The Ohio State University	Columbus	Ohio	United States	43210
3	Fakultní nemocnice Brno	Brno		Czechia
4	Fakultní nemocnice Hradec Králové	Hradec Králové		Czechia
5	Fakultní nemocnice Ostrava	Ostrava		Czechia
6	Všeobecná fakultní nemocnice	Praha		Czechia
7	Hôpital Morvan	Brest		France
8	Centre Jean Bernard - Clinique Victor Hugo	Le Mans		France
9	Hôpital privé du Confluent	Nantes		France
10	Centre Hospitalier Lyon Sud	Pierre-Bénite		France
11	Centre Hospitalier Universitaire Institut Gustave Roussy	Villejuif		France
12	Hospital Universitai Germans Trias i Pujol	Badalona		Spain
13	Hospital de la Santa Creu i Sant Pau	Barcelona		Spain
14	Hospital Universitario 12 de Octubre	Madrid		Spain
15	Complejo Hospitalario de Salamanca	Salamanca		Spain
16	Hospital Universitario Marques de Valdecilla	Santander		Spain

Sponsors and Collaborators

• Oncopeptides AB

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Oncopeptides AB
• ClinicalTrials.gov Identifier: NCT03481556
• Other Study ID Numbers: OP-104
• First Posted: Mar 29, 2018
• Last Update Posted: Mar 7, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Dexamethasone; Dexamethasone acetate; Bortezomib; Melphalan; Daratumumab

Study Results

No Results Posted as of Mar 7, 2022