A Phase II Study of Carfilzomib in Relapsed Waldenström's Macroglobulinemia (WM) IST-CAR-531

NCT01813227 | Completed Phase 2 Results DMC

• 1 other identifier: Pro 3596 (CAR-531)
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety and effectiveness of an investigational study drug called carfilzomib. The investigators want to find out what effects, good and/or bad, it has on patients and their cancer if treatment continues beyond previous carfilzomib treatment study. Carfilzomib (KyprolisTM) is approved by the U.S. Food and Drug Administration (FDA) to be used only in certain U.S. patients with relapsed and refractory multiple myeloma that have tried and failed other therapies. It has not been approved to be used for any other disease or condition. In this study, carfilzomib is referred to as an investigational study drug because it is not approved for use in all patients with multiple myeloma in the United States, and it is not approved by some regulatory authorities (the agencies that are responsible for approving the use of a medicine in a country such as Health Canada). Carfilzomib is a type of drug called a proteasome inhibitor. A proteasome is a protein found within cells that has the important role of identifying and marking damaged proteins that are needed to be destroyed by the cell for survival. The inhibition of the proteasome allows for damaged protein to accumulate within cells. This accumulation of damaged protein causes the cell to die.

Conditions

Waldenstrom Macroglobulinemia

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR) of Carfilzomib in Bortezomib naïve and Bortezomib-exposed Relapsed WM

  The overall response rate (ORR) (rate of patients attaining a Partial Response or a Complete Response). Responses will be based on both serum paraprotein levels by SPEP and bidimensional disease measurements on CT scan for patients with adenopathy/organomegaly/lymphadenopathy. Criteria as per the Recommended Response Criteria for Waldenstrom Macroglobulinemia Complete Response: * Absence of serum monoclonal IgM protein by immunofixation * Normal serum IgM level * Complete resolution of extramedullary disease, i.e., lymphadenopathy and splenomegaly if present at baseline * Morphologically normal bone marrow aspirate and trephine biopsy Partial response (PR) * Monoclonal IgM protein is detectable -≥50% but\<90% reduction in serum IgM level from baseline * Reduction in extramedullary disease, i.e., lymphadenopathy/splenomegaly if present at baseline * No new signs or symptoms of active disease

  Participants will be evaluated every 28 days (1 cycle) until progression or a maximum of 12 cycles (1 year)

Secondary Outcomes (4)

• Number of Patients Experiencing Dose Limiting Toxicity

  Participants will be evaluated for the first 28 days of cycle 1

• Duration of Response in Patients With WM.

  Participants will be evaluated every 28 days (1 cycle) until they experience disease progression, are treated with another therapy, or died, an average of 15 months

• Time to Progression

  Participants will be evaluated every 28 days (1 cycle) until disease progression, an average of 16 months

• Progression Free Survival

  Participants will be evaluated every 28 days (1 cycle) until progression, an average of 19 months

Study Arms (1)

Carfilzomib

EXPERIMENTAL

Carfilzomib 20 mg/m2 on day 1, 2 then 56 mg/m2 days 8, 9 and 15, 16 over 30 minutes every 28 days. Dexamethasone 4 mg (8 mg if \> 45 mg/m2) orally each day of carfilzomib therapy. If less than a partial remission (PR) after 4 cycles, add rituximab 375 mg/m2 on day 16 of each cycle. Patients who meet the criteria for progression prior to 4 cycles of therapy will have rituximab added to their treatment. For patients receiving rituximab, the carfilzomib dose will be decreased to 27 mg/m2. Patients will be treated to maximal response plus 2 additional cycles to a maximum of 12 cycles.

Drug: Carfilzomib; Drug: Rituximab; Drug: Dexamethasone

Interventions

Carfilzomib DRUG

If you decide to participate in the study, you will receive carfilzomib on Days 1, 2, 8, 9, 15, and 16 every 28 days for a minimum of 2 cycles (approximately 2 months). You may receive additional cycles for as long as your disease remains stable or improved or until your study doctor determines that you should stop receiving the study drug or you decide to stop participating in the study.

Also known as: Kyprolis

Carfilzomib

Rituximab DRUG

If you decide to participate in the study, in addition to the carfilzomib and possible dexamethasone administration, If less than a partial remission (PR) after 4 cycles is achieved, rituximab 375 mg/m2 on day 16 of each subsequent cycle will be added to the treatment. Subjects who meet the criteria for progression prior to 4 cycles of therapy will have rituximab 375 mg/m2 weekly for 4 consecutive weeks every 3 cycles added to the treatment. Subjects will be treated to maximal response plus 2 additional cycles to a maximum of 12 cycles. At the beginning of every cycle, your study doctor will see if your general health is satisfactory. You will be asked to report any side effects or problems you have had since the start of the last treatment cycle as well as any medication change(s).

Also known as: Rituxan

Carfilzomib

Dexamethasone DRUG

If you decide to participate in the study, you will receive carfilzomib on Days 1, 2, 8, 9, 15, and 16 every 28 days for a minimum of 2 cycles (approximately 2 months). You may receive additional cycles for as long as your disease remains stable or improved or until your study doctor determines that you should stop receiving the study drug or you decide to stop participating in the study. You will also receive dexamethasone weekly on Days 1, 2, 8, 9, 15 and 16 starting with cycle 1 and continuing every cycle thereafter.

Also known as: Decadron

Carfilzomib

Eligibility Criteria

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

You may qualify if:

• Biopsy proven WM with relapsed/refractory symptomatic disease are eligible for enrollment.
• Bone marrow lymphoplasmacytosis with:
• \> 10% lymphoplasmacytic cells (measured within 28 days prior to registration OR
• Aggregates or sheets of one of the following: lymphocytes, plasma cells or lymphoplasmacytic cells on the bone marrow biopsy (measured within 28 days prior to registration).
• Measurable disease defined as a quantitative IgM monoclonal protein of \>500 mg/dL obtained within 28 days prior to registration
• CD20+ bone marrow or lymph node by immunohistochemistry or flow cytometry obtained within 28 days prior to registration
• Lymph node biopsy must be done \<28 days prior to registration if used as an eligibility criterion for study entry.
• Symptomatic disease, as defined by the IWWM, includes the following criteria: Hemoglobin less than 10 g/dL, platelet count less than 100,000 uL, bulky adenopathy or organomegaly, symptomatic hyperviscosity syndrome, severe neuropathy, amyloidosis, cryoglobulinemia, cold agglutinin disease, or evidence of transformation high-grade non-Hodgkin's lymphoma.
• Patients must not be receiving concurrent steroids \> 10 mg prednisone (or equivalent) per day.
• Prior irradiation is allowed if \> 28 days prior to registration have elapsed since the date of last treatment.
• Women must not be pregnant or breast-feeding due to the fact that the reproductive risk to humans taking carfilzomib is unknown. All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy. A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
• Women of childbearing potential and sexually active males must use an accepted and effective method of contraception throughout the study and for 8 weeks after completion of the study.
• Patients must be \> 18 years old.
• Patients must have ECOG performance status of \< 2.
• Patients may have received prior bortezomib therapy.

You may not qualify if:

• Pre-existing peripheral neuropathy \> grade 2 with pain (CTC version 4.0).
• Hematologic criteria: ANC \< 500/uL, Platelets \< 25,000 uL.
• Renal function: CrCl \< 15 ml/min.
• Active infection requiring intravenous antibiotics
• Known Active hepatitis B or C
• SGOT (AST) and SGPT (ALT) \> 3x institutional ULN
• Direct bilirubin \> 1.5 mg/dL
• Patients must not have any severe and/or uncontrolled medical condition or other conditions that could affect their participation in the study, including, but not restricted to:
• Symptomatic congestive heart failure of New York Heart Association Class III or IV.
• Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 3 months of start of study treatment, serious uncontrolled cardiac arrhythmia or any other clinically significant heart disease.
• Severely impaired lung function as defined as spirometry and DLCO (corrected for Hgb) that is \<50% of the normal predicted value and/or O2 saturation \<88% at rest on room air.
• Active (acute or chronic) or uncontrolled severe infections.

Sponsors & Collaborators

• Hackensack Meridian Health: lead
• Onyx Therapeutics, Inc.: collaborator

Study Sites (1)

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia

Interventions

carfilzomib; Rituximab; Dexamethasone; Calcium Dobesilate

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; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Results Point of Contact

• Title: Joshua Zenreich
• Organization: Hackensack Meridian Health

joshua.zenreich@hmhn.org

5519964248

Study Officials

• David H Vesole, MD, PhD

  John Theurer Cancer Center at Hackensack University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: March 11, 2013
• First Posted: March 18, 2013
• Study Start: April 1, 2013
• Primary Completion: September 1, 2014
• Study Completion: October 1, 2018
• Last Updated: April 13, 2022
• Results First Posted: April 13, 2022

Record last verified: 2022-03

Locations

US (1)