Clinical trial NCT02447055: Allogeneic Stem Cell Transplantation for Patients With Multiple Myeloma
Official title: Allogeneic Stem Cell Transplantation for Patients With Multiple Myeloma: a Pilot Feasibility Study Using a Novel Protocol
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: EARLY_PHASE1
Conditions: Multiple Myeloma
Myeloma-Multiple
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2015-05-18
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Safety and tolerability of regimen as measured by grade and frequency of adverse events
timeFrame: Day +100
Secondary outcomes:
measure: Cumulative incidence and severity of acute GvHD
timeFrame: 6 months
measure: Cumulative incidence and severity of chronic GvHD
timeFrame: 1 year
measure: Non-relapse mortality (NRM)
timeFrame: 1 year
measure: Non-relapse mortality (NRM)
timeFrame: Day +100
measure: Progression-free survival (PFS)
timeFrame: 1 year
measure: Overall survival (OS)
timeFrame: 1 year
measure: Time to neutrophil engraftment
timeFrame: Day +30
measure: Time to platelet engraftment
timeFrame: Day +100
measure: Non-relapse mortality (NRM)
timeFrame: Day +180
Other outcomes:
Locations:
Study officials:
affiliation: Washington University School of Medicine
name: John F DiPersio, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: