Allogeneic Stem Cell Transplantation for Patients With Multiple Myeloma

NCT02447055 | Withdrawn Early Phase 1

• 1 other identifier: 201508102
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to develop a novel platform for allo-SCT in multiple myeloma (MM) with the idea of maximizing anti-myeloma effect with conditioning and minimizing GvHD (graft versus host disease). Specifically, the investigators will use the Flu/Mel (fludarabine and melphalan) regimen. For GvHD prophylaxis, the investigators use the Hopkins PT-Cy (post-transplant cyclophosphamide) platform with the novelty of adding tocilizumab as both an anti-myeloma therapy and as a method to reduce GvHD. IL-6 has an important role in promoting the growth of myeloma cells and progression of disease.

Conditions

Multiple Myeloma; Myeloma-Multiple

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of regimen as measured by grade and frequency of adverse events

  Adverse events will be graded using NCI CTCAE v4.0 and summarized by grade and frequency

  Day +100

Secondary Outcomes (9)

• Cumulative incidence and severity of acute GvHD

  6 months

• Cumulative incidence and severity of chronic GvHD

  1 year

• Non-relapse mortality (NRM)

  1 year

• Non-relapse mortality (NRM)

  Day +100

• Progression-free survival (PFS)

  1 year

Study Arms (1)

Arm 1 (Flu/Mel/PT-Cy & Tac/MMF for certain cases)

EXPERIMENTAL

* Fludarabine 30 mg/m\^2 intravenously (IV) on Days -5, -4, -3, and -2 * Melphalan 140 mg/m\^2 IV on Day -2 * Tocilizumab 8 mg/m\^2 (capped at 800 mg) IV on Day -1 * Stem cell infusion on Day 0 * Cyclophosphamide 50 mg/kg IV on Days +3 and +4 * Tacrolimus 1 mg/day IV on Day +5 (for unrelated \& haploidentical cases) * Mycophenolate mofetil 15 mg/kg orally three times per day on Day +5 (for unrelated \& haploidentical cases) * Filgrastim 10 ug/kg/day subcutaneously until neutrophil recovery starting on Day +5

Biological: Tocilizumab; Drug: Melphalan; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Tacrolimus; Drug: Mycophenolate mofetil; Drug: Filgrastim

Interventions

Tocilizumab BIOLOGICAL

Also known as: Actemra®

Arm 1 (Flu/Mel/PT-Cy & Tac/MMF for certain cases)

Melphalan DRUG

Also known as: Alkeran®, Phenylalanine mustard

Arm 1 (Flu/Mel/PT-Cy & Tac/MMF for certain cases)

Fludarabine DRUG

Also known as: Fludara®, 2-Fluoro-ara-A Monophosphate, 2-Fluoro-ara AMP, FAMP

Arm 1 (Flu/Mel/PT-Cy & Tac/MMF for certain cases)

Cyclophosphamide DRUG

Also known as: Cytoxan®, CPM, CTX, CYT

Arm 1 (Flu/Mel/PT-Cy & Tac/MMF for certain cases)

Tacrolimus DRUG

Also known as: Prograf®, FK-506

Arm 1 (Flu/Mel/PT-Cy & Tac/MMF for certain cases)

Mycophenolate mofetil DRUG

Also known as: CellCept®, Myfortic®

Arm 1 (Flu/Mel/PT-Cy & Tac/MMF for certain cases)

Filgrastim DRUG

Also known as: Granix®, Neupogen®, Granulocyte Colony-Stimulating Factor, G-CSF, Recombinant Methionyl Human G-CSF

Arm 1 (Flu/Mel/PT-Cy & Tac/MMF for certain cases)

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed diagnosis of myeloma.
• Between 18 and 70 years of age (inclusive).
• Karnofsky performance status ≥ 50% or ECOG performance score of ≤ 2 -Completion of last anti-myeloma therapy (if any) must occur at least 14 days before conditioning.
• Must have an HLA-matched sibling, HLA-matched unrelated donor, or a related haploidentical donor:
• Available HLA-matched sibling or unrelated donor must meet the following criteria:
• At least 18 years of age
• HLA donor/recipient match based on at least low-resolution typing per institutional standards (syngeneic donors \[identical twins\] are excluded)
• In the investigator's opinion, is in general good health, and medically able to tolerate leukapheresis required for harvesting stem cells
• No active hepatitis
• Negative for HTLV and HIV
• Not pregnant
• Available haploidentical donor must meet the following criteria:
• Blood-related family member (sibling (full or half), offspring, parent, cousin, niece or nephew, aunt or uncle, or grandparent)
• At least 18 years of age
• HLA-haploidentical donor/recipient match by at least low-resolution typing per institutional standards

You may not qualify if:

• Receiving renal replacement therapy, hemodialysis, or peritoneal dialysis.
• Presence of another concurrent malignancy requiring treatment.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to melphalan, cyclophosphamide, or other agents used in the study.
• Presence of an uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant and/or breastfeeding.
• Previous treatment with tocilizumab (TCZ).
• Immunization with a live/attenuated vaccine within 28 days prior to conditioning.
• Any history of recent serious bacterial, viral, fungal, or other opportunistic infections, precluding a stem cell transplant according to the treating physician.
• Serologic evidence of HIV
• Active infection with Hepatitis A, B, or C. Active infection is defined as serologic positivity and elevated liver function tests.
• History of tuberculosis
• Active infection with EBV as defined as EBV viral load ≥ 10,000 copies per mL of whole blood; EBV viral load testing is only required if the patient has clinical signs or symptoms suggestive of active EBV infection
• Active infection with CMV as defined as CMV viral load ≥ 10,000 copies per mL of whole blood; CMV viral load testing is only required if the patient has clinical signs or symptoms suggestive of active CMV infection
• History of complicated diverticulitis, including fistulae, abscess formation or gastrointestinal (GI) perforation.
• Pre-existing CNS demyelination or seizure disorders

Sponsors & Collaborators

• Washington University School of Medicine: lead

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Multiple Myeloma

Interventions

tocilizumab; Melphalan; fludarabine; fludarabine phosphate; Cyclophosphamide; Tacrolimus; Mycophenolic Acid; Filgrastim; Granulocyte Colony-Stimulating Factor

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; Phosphoramide Mustards; Phosphoramides; Organophosphorus Compounds; Macrolides; Lactones; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Proteins; Biological Factors

Study Officials

• John F DiPersio, M.D., Ph.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 13, 2015
• First Posted: May 18, 2015
• Study Start: December 1, 2015
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: July 12, 2016

Record last verified: 2016-07