Allogeneic Stem Cell Transplantation for Patients With Multiple Myeloma

NCT ID: NCT02447055

Last Updated: 2016-07-12

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: EARLY_PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-31
• Study Completion Date: 2016-06-30

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

• 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

Group Type: EXPERIMENTAL

Tocilizumab

Intervention Type: BIOLOGICAL

Melphalan

Intervention Type: DRUG

Fludarabine

Intervention Type: DRUG

Cyclophosphamide

Intervention Type: DRUG

Tacrolimus

Intervention Type: DRUG

Mycophenolate mofetil

Intervention Type: DRUG

Filgrastim

Intervention Type: DRUG

Interventions

Tocilizumab

Intervention Type: BIOLOGICAL

Melphalan

Intervention Type: DRUG

Fludarabine

Intervention Type: DRUG

Cyclophosphamide

Intervention Type: DRUG

Tacrolimus

Intervention Type: DRUG

Mycophenolate mofetil

Intervention Type: DRUG

Filgrastim

Intervention Type: DRUG

Other Intervention Names

Actemra®; Alkeran®; Phenylalanine mustard; Fludara®; 2-Fluoro-ara-A Monophosphate; 2-Fluoro-ara AMP; FAMP; Cytoxan®; CPM; CTX; CYT; Prograf®; FK-506; CellCept®; Myfortic®; Granix®; Neupogen®; Granulocyte Colony-Stimulating Factor; G-CSF; Recombinant Methionyl Human G-CSF

Eligibility Criteria

Inclusion Criteria

• 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

OR

• 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
• 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
• Normal bone marrow and organ function as defined below within 14 days prior to first study drug dose (conditioning regimen):

• Total bilirubin ≤ 2.5 mg/dl
• AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN
• Creatinine ≤ 2.0 x ULN OR estimated creatinine clearance ≥ 30 mL/min/1.73 m2 by Cockcroft-Gault Formula (See Appendix C)
• Oxygen saturation ≥ 90% on room air
• LVEF ≥ 40%
• FEV1 and FVC ≥ 40% predicted, DLCOc ≥ 40% predicted
• Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry through Day +100 visit. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
• Able to understand and willing to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria

• 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
• Major surgery within preceding 8 weeks
• Body weight >150kg
• History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John F DiPersio, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Related Links

http://www.siteman.wustl.edu

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

Other Identifiers

201508102

Identifier Type: -

Identifier Source: org_study_id