First Autologous Transplant on Minimal Residual Disease Markers in Previously Untreated Myeloma Undergoing Initial Treatment With Velcade

Phase 2

Completed

Conditions: Multiple Myeloma

Interventions: Drug: VELCADE
Drug: DVT prophylaxis
Drug: Lenalidomide
Drug: Liposomal doxorubicin
Drug: Dexamethasone
Drug: Bisphosphonates

Registration Number: NCT01215344

Lead Sponsor: Vanderbilt-Ingram Cancer Center

Brief Summary: The purpose of this study is to study the MRD status after VELCADE based induction therapy (VELCADE, lenalidomide, dexamethasone or VELCADE, liposomal doxorubicin, dexamethasone) in patients with previously untreated multiple myeloma and study the impact of HDC and ASCT on MRD status post-transplant. Our hypothesis is that MRD-status will continue to increase significantly at 3 months post-transplant and will validate that HDC and ASCT needs to be performed even when patients have achieved major response after induction therapy with novel agents.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 36

Inclusion Criteria

Confirmed Multiple Myeloma as defined below within 120 days of starting cycle 1:

Bone marrow plasmacytosis with ≥ 10% plasma cells or sheets of plasma cells or biopsy proven plasmacytoma
Presence of M protein in serum or urine or both. Conventional M spike, serum free light chains, or 24 hour urine study. Non-secretory myeloma is not eligible for this study.
In addition patient must have one of the following organ dysfunction criteria
Hypercalcemia
Renal insufficiency
Anemia
Bone disease manifested by lytic lesion or osteoporosis (if osteoporosis is the only organ dysfunction criteria then BM should have ≥ 30% plasma cells)
Confirmed Multiple myeloma as defined above within 90 days of starting cycle 1
The following study assessments must be fulfilled and must be obtained with four weeks of starting cycle 1
Hemoglobin > 7 g/dL, Platelet count > 75 X 10 to 9th power/L, and Absolute neutrophil count > 1 X 10 to 9th power/L
Creatinine <2.5 mg/dL or calculated creatinine clearance > 30 ml/min/1.72 m2
Bilirubin ≤ 1.5 mg/dL X ULN
SGPT (ALT) and SGOT (AST) ≤ 2.5 times the upper limit of normal
Ejection fraction ≥ 45% as measured by a MUGA scan or 2 D echocardiogram
Pulmonary function tests show >60% predicted values for FVC, FEV1, and DLCO FEV1 must be > 1 liter.
No prior systemic therapy with the exception of bisphosphonates for MM
Prior glucocorticoid therapy for the treatment of multiple myeloma is not permitted EXCEPT if used in conjunction with palliative radiation to prevent vasogenic edema. In that case steroids should have been used for less than 7 days. Prior steroid use for non-malignant disorders is permitted and should have been restricted to less than the equivalent of prednisone 10 mg per day. Prior or concurrent topical or localized steroid therapy to treat non-malignant disorders is permitted
Prior palliative and/ or localized radiation therapy is permitted provided at least 4 weeks have passed from date of last radiation therapy to starting cycle 1.
Patients with prior solitary plasmacytoma treated with radiation therapy with curative intent are eligible if the disease has now progressed to active multiple myeloma and meeting all eligibility criteria for the protocol
ECOG PS 0, 1 or 2
For women of childbearing potential a negative serum pregnancy test is required within 4 weeks of starting cycle 1 and then every 4 weeks during the first 4 cycles of induction therapy
Women of child bearing potential must be willing to refrain from sexual intercourse or willing to employ a dual method of contraception, one of which is highly effective (IUD, birth control pills, tubal ligation or partner's vasectomy) and another additional method (condom, diaphragm, or cervical cap) during the entire course of the study (start of therapy until 30 days after stem cell transplant).
Sexually active males should be willing to use a condom (even if they have had a prior vasectomy) while having intercourse with any women during the course of the study (start of therapy until 30 days after stem cell transplant).
Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.

Exclusion Criteria

Patients with smoldering myeloma or monoclonal gammopathy of unknown significance are not eligible
Age > 70 years or < 18 years is not eligible
Patient has > 1.5 × ULN Total Bilirubin
Grade 2 or higher peripheral neuropathy due to ANY cause
High index of suspicion of primary amyloid light chain (AL) amyloidosis.
Patients with uncontrolled inter-current illness including uncontrolled hypertension, symptomatic congestive heart failure, unstable angina, uncontrolled cardiac arrhythmia, uncontrolled psychiatric illness or social situation that would limit compliance or a prior history of Steven Johnson syndrome
Patients must not have a history of current or previous deep vein thrombosis or pulmonary embolism regardless of whether or not the patient is receiving anticoagulation therapy
Female patients who are breastfeeding or pregnant.
Patients known to be HIV positive
Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (see section 31.3), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
Patient has hypersensitivity to VELCADE, boron or mannitol.
Patient has received other investigational drugs within 14 days before enrollment
Serious medical or psychiatric illness likely to interfere with participation in this clinical study.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
VDD	DVT prophylaxis	VELCADE, liposomal doxorubicin, dexamethasone
VRD	Lenalidomide	VELCADE, Lenalidomide, Dexamethasone
VDD	Dexamethasone	VELCADE, liposomal doxorubicin, dexamethasone
VRD	DVT prophylaxis	VELCADE, Lenalidomide, Dexamethasone
VDD	VELCADE	VELCADE, liposomal doxorubicin, dexamethasone
VDD	Liposomal doxorubicin	VELCADE, liposomal doxorubicin, dexamethasone
VRD	VELCADE	VELCADE, Lenalidomide, Dexamethasone
VRD	Dexamethasone	VELCADE, Lenalidomide, Dexamethasone
VRD	Bisphosphonates	VELCADE, Lenalidomide, Dexamethasone

Primary Outcome Measures

Name	Time	Method
The Percent of Patients With Minimal Residual Disease (MRD) Status Changing to Negative at Day 100 (Post-AHCT), Among Patients With MRD Positive at the End of Induction (EOI).	6-months post ASCT	Patients were treated with induction therapy (VRD) followed by autologous hematopoietic cell transplant (AHCT). MRD status of a patient with at least partial response was evaluated at the end of induction (EOI) and day 100 (post-AHCT). MRD of a patient is measured by seven-color flow cytometry.

Secondary Outcome Measures

Name	Time	Method
Progression Free Survival by MRD Status at Day 100.	up to 7 years	Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Trial Locations

Locations (2): Vanderbilt-Ingram Cancer Center
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Nashville, Tennessee, United States
University of Tennessee Cancer Institute, Boston Baskin Cancer Group
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Memphis, Tennessee, United States