Carfilzomib and Melphalan Before Stem Cell Transplant in Treating Patients With Multiple Myeloma

NCT01842308 | Completed Phase 1 Results DMC

• 3 other identifiers: MC1185NCI-2013-00550P30CA015083
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

Brief Summary

This phase I/II trial studies the side effects and best dose of carfilzomib when given together with melphalan and to see how well they work in treating patients with multiple myeloma before stem cell transplant. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving carfilzomib together with melphalan may kill more cancer cells.

Conditions

DS Stage I Plasma Cell Myeloma; DS Stage II Plasma Cell Myeloma; DS Stage III Plasma Cell Myeloma; Refractory Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (2)

• Determine Maximum Tolerated Dose by the Number of Patients With a DLT Per Dose Level

  Will be defined as the dose level below the lowest dose that induces dose-limiting toxicity(DLT) in at least one-third of patients. For this study, a DLT is any of the following during the first 2 cycles of treatment; Absolute neutrophil count engraftment\* delayed beyond day 21 or Platelet engraftment\* delayed beyond day 30, grade 3+ related sensory or motor neuropathy, or grade 4+ related non-neurologic or non-hematologic adverse event(excluding nausea, vomiting, and diarrhea. Reported below are the number of patients who experienced a DLT.

  Up to day 30

• Percentage of Patients With Complete Responses, Defined as a Complete Response Noted as the Objective Status on Two Consecutive Evaluations (Phase II)

  The percentage of successes will be estimated by the number of successes divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success percentages will be calculated.

  Up to 5 years

Secondary Outcomes (3)

• Adverse Event Rate, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0

  Up to 5 years

• Complete Response Rate at Day 100

  At day 100

• Progression Free Percentage at 1 and 2 Years Post Registration

  At 1 year and 2 years

Study Arms (1)

Treatment

EXPERIMENTAL

CONDITIONING: Patients receive carfilzomib IV over 30 minutes on days -6, -5, -2, and -1. Patients also receive melphalan IV over 1 hour on days -4 and -3. TRANSPLANT: Patients undergo autologous stem cell transplant on day 0.

Procedure: Autologous Bone Marrow Transplantation; Procedure: Autologous Hematopoietic Stem Cell Transplantation; Drug: Carfilzomib; Other: Laboratory Biomarker Analysis; Drug: Melphalan

Interventions

Autologous Bone Marrow Transplantation PROCEDURE

Undergo autologous stem cell transplant

Also known as: ABMT, Autologous Bone Marrow Transplant, Autologous Marrow Transplantation

Treatment

Autologous Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo autologous stem cell transplant

Also known as: Autologous Hematopoietic Cell Transplantation, Autologous Stem Cell Transplantation

Treatment

Carfilzomib DRUG

Given IV

Also known as: Kyprolis, PR-171

Treatment

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment

Melphalan DRUG

Given IV

Also known as: Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine mustard, L-Sarcolysin, L-Sarcolysin Phenylalanine mustard, L-Sarcolysine, Melphalanum, Phenylalanine Mustard, Phenylalanine Nitrogen Mustard, Sarcoclorin, Sarkolysin, WR-19813

Treatment

Eligibility Criteria

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

You may qualify if:

• Serum creatinine =\< 2 mg/dL
• Absolute neutrophil count \>= 1000/uL
• Platelet count \>= 50,000/uL
• Hemoglobin \>= 8.0 g/dL
• Diagnosis of symptomatic MM
• Measurable disease of multiple myeloma at the time of baseline values for disease assessment as defined by at least one of the following:
• Serum monoclonal protein \>= 1.0 g/dL
• \>= 200 mg of monoclonal protein in the urine on 24 hour electrophoresis
• Serum immunoglobulin free light chain \>=10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
• Bone marrow plasma cells \>= 30%
• NOTE: For patients with no relapse prior to transplant, measurable disease at the time of diagnosis
• NOTE: For patients who have had a disease relapse prior to transplant, measurable disease at the time of the most recent relapse immediately prior to transplant; NOTE: If the patient had treatment for the relapsed disease prior to transplant, the patient must have measurable disease at the time of relapse prior to this therapy
• Patient is considered for autologous stem cell transplantation with full dose melphalan (200 mg/m\^2)
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
• Recovered from toxicity of previous chemotherapy (excludes grade 1 neurotoxicity and hematological toxicity)

You may not qualify if:

• Prior autologous or allogeneic bone marrow/peripheral blood stem cell transplant
• More than two prior regimens for therapy of MM
• Myocardial infarction within 6 months prior to enrollment, or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; NOTE: Prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
• Seroreactivity for human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV) I or II, hepatitis B virus (HBV), hepatitis C virus (HCV)
• Other active malignancy \< 2 years prior to registration; EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: If there is a history or prior malignancy, they must not be receiving other specific treatment for their cancer
• Any of the following:
• Pregnant women or women of reproductive capability who are unwilling to use effective contraception
• Nursing women
• Men who are unwilling to use a condom (even if they have undergone a prior vasectomy) while having intercourse with any woman, while taking the drug and for 28 days after stopping treatment
• Other co-morbidity, which would interfere with patient's ability to participate in the trial, e.g. uncontrolled infection, uncompensated lung disease
• Concurrent chemotherapy, radiotherapy, or any ancillary therapy considered investigational; NOTE: Bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment
• Known allergies to any of the components of the investigational treatment regimen or required ancillary treatments

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

carfilzomib; Melphalan

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)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Suzanne R. Hayman, M.D
• Organization: Mayo Clinic

hayman.suzanne@mayo.edu

(855) 776-0015

Study Officials

• Suzanne Hayman

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2013
• First Posted: April 29, 2013
• Study Start: June 4, 2013
• Primary Completion: October 11, 2017
• Study Completion: October 28, 2019
• Last Updated: September 1, 2020
• Results First Posted: September 1, 2020

Record last verified: 2019-10

Locations

US (2)