2006-32 Phase II Study of Rapidly Recycled High Dose DTPACE

2006-32: Phase II Study of Rapidly Recycled High Dose DTPACE (HD-DTPACE) for Untreated or Previously Treated, High-Risk Multiple Myeloma (MM)

This study is being done in an attempt to improve the remission rate and the survival time for subjects with high-risk myeloma. It is hoped that by giving higher doses of commonly used chemotherapy drugs and by giving courses closer together (before the myeloma comes back or gets worse), subjects in this study will have better outcomes.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: DTPACE

Detailed Description

This study has the following goals:

• To find out how many subjects treated with high dose DTPACE (Dexamethasone, Thalidomide, CisPlatin, Adriamycin, Cyclophosphamide, and Etoposide. (HD DTPACE) on this protocol will have a complete response or near complete response that lasts for 6 months or longer.
• In subjects achieving a response, to find out how long the response will last.
• To learn more about the side effects of this treatment.

Up to 75 subjects, male or female, age 18 and older, regardless of race or ethnicity, will participate in this study at the University of Arkansas for Medical Sciences (UAMS) only.

The treatment in this study is divided into 3 parts

• High dose DTPACE and stem cell collection if you do not already have sufficient stem cells stored.
• High dose DTPACE and stem cell re-infusion.
• Velcade, Thalidomide, Dexamethasone (sometimes known as VTD) Maintenance therapy.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with multiple myeloma, treated or untreated, with the presence of one or more of the high risk features as defined below.

High risk by gene expression profiling at any time prior to enrollment:

1. PROLIFERATION signature, MMSET/FGFR3, c-MAF/MAF-B gene groups or

2. High risk score based on University of Arkansas Myeloma Institute for Research and Therapy (MIRT) 70 gene model.

   • Abnormal metaphase cytogenetics at any time prior to enrollment, or

   • Lactate Dehydrogenase (LDH) > 250 IU/L (upper limit normal) at any time prior to enrollment

     • Zubrod ≤ 2, unless due to symptoms of MM.
     • Patients must be < 75 years of age at the time of registration.
     • Patient must have signed an Institutional Review Board (IRB)-approved informed consent and understand the investigational nature of the study.
     • Negative serology for HIV.
     • Patients must not have a history of chronic obstructive or chronic restrictive pulmonary disease. Patients must have adequate pulmonary function studies > 50% of predicted on mechanical aspects (FEV1, forced vital capacity (FVC), etc) and diffusion capacity (DLCO) > 50% of predicted. Patients unable to complete pulmonary function tests because of myeloma-related chest pain, must have a high resolution CT scan of the chest and must also have acceptable arterial blood gases defined as P02 greater than 70.
     • Patients with recent (< 6 months) myocardial infarction, unstable angina, difficult to control congestive heart failure, uncontrolled hypertension, or difficult to control cardiac arrhythmias are ineligible. Ejection fraction by echocardiogram (ECHO) or must be > 40% and must be performed within 60 days prior to registration, unless the patient has received chemotherapy within that period of time (dexamethasone and thalidomide excluded), in which case the left ventricular ejection fraction (LVEF) must be repeated.
     • No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease free for at least three years. Prior malignancy is acceptable provided there has been no evidence of disease within the three-year interval or if the malignancy is considered much less life threatening than the myeloma.
     • Pregnant or nursing women may not participate. Women of childbearing potential must have a negative pregnancy documented within one week of registration. Women/men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
     • Patients must be able to receive full doses of HD-DTPACE, in the opinion of the treating investigator, with the exception that patients with serum creatinine > 1.5 mg/dL will receive modified doses of cisplatin.

Exclusion Criteria:

• Fever or active infection requiring intravenous antibiotics within 72 hours from baseline.
• Liver function abnormalities with total bilirubin more than twice the upper limit of normal or aspartate amino transferase (AST)/alanine amino trasferase (ALT) more than three times the upper limit of normal.
• Severe renal dysfunction, defined as a creatinine > 3mg/dl or a creatinine clearance of <30ml/min.
• Platelet count < 30,000/mm3, or absolute neutrophil count (ANC) < 1,000/μl.
• Clinically significant hepatic dysfunction as noted by direct bilirubin or AST >3 times the upper normal limit or clinically significant concurrent hepatitis.
• New York Hospital Association (NYHA) Class III or Class IV heart failure.
• Poorly controlled hypertension, diabetes mellitus, or other serious medical illness or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol.
• Prior adriamycin exposure > 450 mg/m2.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HD DTPACE; DTPACE	Drug: DTPACE; Dexamethasone 200 mg Intravenous Infusion "Piggy-Back" (IVPB) Days 1-7; Thalidomide 200 mg by mouth (PO) Days 1-7; Cisplatin 15mg/m2 Days 1-4 (modify for renal insufficiency); Adriamycin 15 mg/m2 Days 1-4; Cyclophosphamide 600 mg/m2 Days 1-4; Etoposide 60 mg/m2 Days 1-4

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects Treated With (HD DTPACE Obtain a Complete Response or Near Complete Response That Lasts for 6 Months or Longer.	Complete Response (CR) defined as all of the following for a minimum of 2 months: a) absence of urine and serum M-components by immunofixation; b) bone marrow should be adequately cellular (>20%); c) normal serum calcium; d) no new bone lesions or enlargement of existing lesions. Near Complete Response included all elements of CR except immunofixation studies remained positive.	12 months

Collaborators and Investigators

• Sponsor: University of Arkansas
• Investigators: Principal Investigator: Frits van Rhee, MD, PhD, University of Arkansas

Study record dates

Study Major Dates

• Study Start: April 1, 2007
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: December 18, 2007
• First Submitted That Met QC Criteria: December 18, 2007
• First Posted (Estimate): December 20, 2007

Study Record Updates

• Last Update Posted (Actual): November 20, 2017
• Last Update Submitted That Met QC Criteria: October 17, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: 2006-32 (Other Identifier: Institutional Review Board, Dongdaemun Hospital)