Non-myeloablative Allogeneic Transplantation for the Treatment of Multiple Myeloma

NCT00185614 | Completed Phase 2 Results DMC

• 3 other identifiers: IRB-1337875190BMT109
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

Brief Summary

Mixed chimerism transplantation is an approach to allogeneic transplants that attempts to decrease regimen-related toxicity by using non-myeloablative preparatory regimens; establish mixed chimerism using low dose total body irradiation along with immunosuppression using cyclosporine and mycophenolate mofetil; suppress graft-vs-host and host-vs-graft reactions to allow a mixed chimeric state to be established, encourage tolerance and prevent graft-vs-host disease (GvHD) during the mixed chimerism period and use donor lymphocyte infusions to convert the patient to a full chimera while developing a graft-vs-tumor effect.

Conditions

Blood Cancer; Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Event-free Survival (EFS)

  Event-free survival (EFS) as determined for all participants who received the initial Auto-HCT treatment. "Event" was defined as any of the following within 3 years of the participant's last infusion of Auto-HCT or Allo-HCT: relapse; death; or last follow-up if there is no data to document the participant remained alive at 3 years.

  3 years

Secondary Outcomes (4)

• Relapse Rate

  3 years

• Overall Survival (OS)

  3 years

• Acute Graft-vs-Host-Disease (aGvHD)

  6 months

• Chronic Graft-vs-Host-Disease (cGvHD)

  3 years

Study Arms (1)

Auto- then Allo-HCT

EXPERIMENTAL

Auto-HCT mobilization is cyclophosphamide 4 g/m2 + filgrastim 10 µg/kg/day for peripheral blood progenitor cell (PBPC) collection by apheresis. Transplant conditioning is high-dose melphalan 200 mg/m2, followed by PBPC infusion as melphalan rescue \[ie, autologous hematopoietic cells transplant (Auto-HCT)\]. Post-infusion support is filgrastim 5 µg/kg/day, starting 6 days after melphalan. Stable/responsive disease at 4 weeks continues to allogenic HCT (Allo-HCT) from sibling donor fully-matched for human leukocyte antigen (HLA). Allo-HCT conditioning is total body irradiation (TBI) 200 centigray (cGy) + cyclosporine (CSP) 6.25 mg/kg + mycophenolate mofetil (MMF) 15 mg/kg. Donor mobilization is filgrastim 16 µg/kg/day on day -4 to Day 0; apheresis collections on Day -1 \& Day 0, to a target of \> 5 x 10e6 CD34 cells/kg. Allo-HCT is infused to participant on Day 0, with premedication hydrocortisone 100 mg IV \& diphenhydramine 50 mg IV. CSP tapering on Day 56 to Day 180, adjusted as needed.

Procedure: Autologous hematopoietic cell transplant (Auto-HCT); Procedure: Allogeneic hematopoietic cell transplant (Allo-HCT); Drug: Cyclophosphamide; Drug: Filgrastim; Drug: Melphalan; Radiation: Total body irradiation (TBI); Procedure: Cyclosporine (CSP); Drug: Mycophenolate Mofetil (MMF)

Interventions

Autologous hematopoietic cell transplant (Auto-HCT) PROCEDURE

The target cell dose is 2.6 x 10e6 CD34+ cells/kg

Auto- then Allo-HCT

Allogeneic hematopoietic cell transplant (Allo-HCT) PROCEDURE

The target cell dose is 5 x 10e6 CD34 cells/kg

Auto- then Allo-HCT

Cyclophosphamide DRUG

Cyclophosphamide administered intravenously (IV) at 4 mg /m² mobilize peripheral blood progenitor cells (PBPC) for autologous re-infusion

Also known as: Cytoxan, Neosar

Auto- then Allo-HCT

Filgrastim DRUG

* Filgrastim 10 µg/kg/day to mobilize peripheral blood progenitor cells (PBPC) for autologous re-infusion (Auto-HCT) * Filgrastim 5 µg/kg/day starting 6 days after melphalan (Day 4 after Auto-HCT) * Filgrastim 16 µg/kg/day to mobilize donor peripheral blood progenitor cells (PBPC) for allogeneic transplant (Allo-HCT)

Also known as: Neupogen, Granulocyte-colony stimulating factor (G-CSF)

Auto- then Allo-HCT

Melphalan DRUG

Melphalan 200 mg/m2 (high-dose) intravenously as conditioning for Auto-HCT

Also known as: Melphalan hydrochloride, Melphalan HCl

Auto- then Allo-HCT

Total body irradiation (TBI) RADIATION

200 centigray (cGy) total body irradiation delivered on Day 0

Auto- then Allo-HCT

Cyclosporine (CSP) PROCEDURE

Cyclosporine administered twice-daily by mouth at a dose of 6.25 mg/kg from Day -3 through Day 56

Also known as: Cyclosporine A

Auto- then Allo-HCT

Mycophenolate Mofetil (MMF) DRUG

Mycophenolate mofetil will begin at 15 mg/kg twice-daily by mouth from Day 0 to Day 27

Also known as: CellCept

Auto- then Allo-HCT

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Multiple myeloma, early Stage II-III or relapsed / progression after initial treatment of Stage I disease
• Patient has HLA-identical sibling donor
• Age ≤ 70 years
• No prior therapy which would preclude the use of low-dose total body irradiation
• Pathology review and diagnosis confirmation by Stanford University Medical Center
• Karnofsky performance status (KPS) \> 70%
• DLCO ≥ 60% predicted
• ALT and AST \< 2 x upper limit of normal (ULN)
• Total bilirubin \< 2 mg/dL
• Serum creatinine \< 2.0, or 24-hour creatinine clearance ≥ 60 mL/min
• HIV-negative
• Signed informed consent document

You may not qualify if:

• Smoldering multiple myeloma; monoclonal gammopathy of unknown significance; or primary amyloidosis
• Severe psychological or medical illness
• Prior allogeneic hematopoietic cell transplantation
• Pregnant or lactating
• Age ≥ 17
• HIV-seronegative
• Signed informed consent document
• Serious medical or psychological illness
• Pregnant or lactating
• Prior malignancies within the last 5 years, except for non-melanoma skin cancers

Sponsors & Collaborators

• Wen-Kai Weng: lead

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Hematologic Neoplasms; Multiple Myeloma

Interventions

Cyclophosphamide; Filgrastim; Granulocyte Colony-Stimulating Factor; Melphalan; Whole-Body Irradiation; Cyclosporine; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Radiotherapy; Therapeutics; Investigative Techniques; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Results Point of Contact

• Title: Wen-Kai Weng, MD; Associate Professor of Medicine
• Organization: Stanford University School of Medicine

wkweng@stanford.edu

650-723-7689

Study Officials

• Wen-Kai Weng, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: September 12, 2005
• First Posted: September 16, 2005
• Study Start: August 1, 2000
• Primary Completion: April 1, 2009
• Study Completion: April 1, 2010
• Last Updated: January 18, 2018
• Results First Posted: January 18, 2018

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)