a Clinical Trial of Efficacy and Safety of the Holistic Treatment of Young High-risk Multiple Myeloma Patients

Multiple Myeloma Clinical Trial

Official title:

Phase II Open Lable Clinical Study Efficacy and Safety of the Holistic Treatment for Young Patients With High-Risk Multiple Myeloma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04008888
• Other study ID #: IHBDH-IIT2016011
• Status: Recruiting
• Phase: N/A
• Start date: January 5, 2018
• Est. completion date: August 1, 2020

Study information

• Verified date: July 2019
• Source: Institute of Hematology & Blood Diseases Hospital
• Contact: WEI W SUI, Dr.
• Phone: 86-022-23909171
• Email: suiweiwei[@]ihcams.ac.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The clinical trial was conducted in a cohort of young, high-risk myeloma patients who were designed to receive a combination of high-dose chemotherapy with allogeneic or autologous hematopoietic stem cell transplantation. The objective was to assess the progression free survival (PFS), overall survival (OS),and overall response rate (ORR) of the overall treatment.

Description:

50 cases of HR-NDMM patients were divided into two groups nonrandomizedly. TE group received hematopoietic stem cell transplantation after induction therapy. Allo-sct for the young patients with suitable donors, Asct for the others. TNE group received consolidation therapy after induction therapy. All patients received PI-based maintenance therapy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: August 1, 2020
• Est. primary completion date: January 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

1. Clinical diagnosis of high-risk multiple myeloma

In addition, patients must meet at least one of the following criteria I-IX (I-VIII at time of diagnosis or pre-autograft):

I.Complex karyotype

II.Fluorescent in situ hybridization (FISH) translocation 4:14 or 14:16,

III.FISH translocation 1q21,

IV.FISH deletion 17p,

V.R-ISS III stage,

VI.Two or more high-risk cytogenetic abnormalities exist

VII.Plasma cell leukemia

VIII.Extramedullary plasmacytoma

IX.Recurrent or non-responsive (less than partial remission [PR]) MM after at least 4 cycles of PI/IMids-based chemotherapy

2. candidate for high-dose chemotherapy with stem cell transplantation

3. ECOG performance status score of 0,1,or2 -

Exclusion Criteria:

1. The current diagnosis of smoldering multiple myeloma, monoclonal gammopathy of undetermined significance of disease, Waldenstr o m macroglobulinemia.

2. during the first 5 years of the study, there were no other malignancies, including basal cell carcinoma or in situ cervical cancer.

3. according to the National Cancer Institute general toxicity criteria (NCI CTC), subjects had peripheral neuropathy of grade 2 or above:

4. were enrolled within 6 months before had a myocardial infarction, or New York Heart Association (NYHA) III or IV heart failure ,uncontrolled angina, uncontrolled severe ventricular arrhythmias or ECG evidence of acute ischemia or conduction system abnormalities and activity the clinical significance of pericardial disease, or cardiac amyloidosis -

Related Conditions & MeSH terms

• 1Q21 Amplification
• Complex Karyotype
• Extramedullary Plasmacytoma
• Leukemia, Plasma Cell
• Loss of Chromosome 17p
• Multiple Myeloma
• Neoplasms, Plasma Cell
• Plasma Cell Leukemia
• Plasmacytoma
• t(14;16)
• T(14;20)
• t(4;14)

Intervention

Procedure:
• Allogeneic Hematopoietic Stem Cell Transplantation
Allogeneic Stem Cell Transplant: Day 0 Infusion of allogeneic peripheral blood stem cells. For the allogeneic matched-related donors peripheral blood stem cells will be harvested with GCSF mobilization and infused fresh to the recipients.
• Autologous Hematopoietic Stem Cell Transplantation x 1 or x 2
Autologous hematopoietic stem cell transplantation :Stem cell mobilization with granulocyte colony-stimulating factor (GCSF) at a dose of 10 µg/kg/day followed collecting CD34+ peripheral blood stem cells . Day 0 Infusion of autologous stem cells. Patients during 3-6 months after the 1st SCT will undergo a 2nd SCT. Patients who had not enough PBSC will undergo a 1st SCT.

Drug:
• Melphalan Given IV
conditioning regimen: autologous ARM: Day -2 Melphalan 200 mg/m^2/day IV over 30 minutes. allogeneic ARM: Day -4, Day -3 Melphalan 70 mg/m^2/day IV over 30 minutes
• Fludarabine Injection
conditioning regimen:Days -6,-5,-4,-3 Fludarabine 30 mg/m^2/day IV
• PI and dexamethasone as maintenance therapy
Bortezomib and dexamethasone(VD),Ixazomib and dexamethasone(ID)
• PI+IMids+Dexamethasone as Consolidated Chemotherapy
Oral lenalidomide at the starting dose of 25mg on days 1-21 every 28 days or days 1-14 every 21 days. Dexamethasone at 20mg twice weekly on days 1,2,4,5,8,9,11&12 of each 21-day.

Locations

Country	Name	City	State
China	Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences	Tianjin	Tianjin

Sponsors (1)

Lead Sponsor	Collaborator
Institute of Hematology & Blood Diseases Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	progression free survival(PFS)	PFS is defined as the duration from the data of registration to either progressive disease or death, whichever comes first.	1 Year post-autograft
Secondary	overall response(ORR)	ORR is defined as the proportion of subjects who achieve PR to better rate, according to the IMWG criteria	1 Year post-autograft
Secondary	overall survival(OS)	OS is defined as the duration from the data of registration to death.If the subject is alive, the data will be censored as being alive; the vital status is unknown as last known.	1 Year post-autograft
Secondary	Number of Patients With Grade II-IV Acute Graft-versus-Host-Disease and/or Chronic Extensive Graft-versus-Host-Disease	aGVHD The diagnosis of aGVHD is identified through various stages and grading of the disease related to Skin (Rash), Gut (Diarrhea, Nausea/vomiting and/or anorexia) and the liver (Bilirubin) assessed by severity and grading scale outlined in the section Grafts vs Hosts by Sullivan (1999).; GVHD Grades Grade I: 1-2 Skin Rash; No gut or liver involvement Grade II: Stage 1-3 Skin rash; Stage 1 gut and/or stage 1 liver involvement Grade III: Stage 2-4 gut involvement and/or stage 2-4 liver involvement with or without rash Grade IV: Pattern and severity of GVHD similar to grade 3 with extreme constitutional symptoms or death cGVHD The diagnosis of cGVHD requires at least one manifestation that is distinctive for chronic GVHD as opposed to acute GVHD. In all cases, infection and others causes must be ruled out in the differential diagnosis of chronic GVHD.	1 year post-allograft
Secondary	Non-relapse Mortality (NRM)	Number of patients with non-relapse mortalities	1 year post-allograft
Secondary	Number of Patients Who Had Infections	Number of patients who had infections	1 Year post-autograft