Overview

Allogeneic Stem Cell Transplantation for Patients With Multiple Myeloma

Status:
Withdrawn
Trial end date:
2016-06-01
Target enrollment:
0
Participant gender:
All
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.
Phase:
Early Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Washington University School of Medicine
Treatments:
Cyclophosphamide
Fludarabine
Fludarabine phosphate
Lenograstim
Melphalan
Mycophenolate mofetil
Mycophenolic Acid
Sargramostim
Tacrolimus
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.