Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Lenalidomide

Tacrolimus

Sirolimus

Immunosuppressive Agents

Immunologic Factors

Calcineurin Inhibitors

Enzyme Inhibitors

Angiogenesis Inhibitors

Growth Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Clotrimazole

Miconazole

Antifungal Agents

Use sirolimus and tacrolimus as GvHD prophylaxis with sirolimus and lenalidomide as post-transplant maintenance

Start on Day -3 and begin tapering on Day +100 until Day +180.

Start between Day +30 and +120 and continue for 1 year.

Sherif Farag, MD, PhD

One of the complications that can occur after a stem cell transplant is called graft versus host disease (GVHD). Another complication is that multiple myeloma may come back (relapse). In this study, a drug called lenalidomide will be started 1-2 months after a transplant, or possibly later depending on recovery of your side effects. Lenalidomide and sirolimus have been shown to work together against multiple myeloma. Therefore, lenalidomide will be combined with sirolimus with the hope that this will help prolong the amount of time the disease is in remission. Researchers hope these steps will help prolong the amount of time the multiple myeloma is in remission and will decrease the chance of GvHD.

Allo Transplant Followed by Lenalidomide and Sirolimus Maintenance in High-Risk Multiple Myeloma (MM)

Phase I/II Trial of Allogeneic Peripheral Blood Stem Cell Transplantation Followed by Maintenance Therapy With Lenalidomide and Sirolimus in Patients With High-Risk Multiple Myeloma

The number of patients who had a DLT during the dose finding/confirming portion (Phase I) of the trial for the safety of the combination of sirolimus, tacrolimus and lenalidomid. Patients will be monitored for 28 days (a cycle) to determine whether a DLT is experienced for the specific dose level.

Percent of patients and the 95% Binomial Confidence interval who were alive and free of progression at 12 months following transplant for the patients in Phase II. Progression will be based on International Myeloma Working Group criteria where patients may meet any one of the following criteria - increase of 25% or more in serum or urine M-protein from baseline, Serum M-protein and/or the absolute increase must be \>=0.5 g/dl, Urine M-protein and/or absolute increase must be \>=200 mg/24 hours, development of new bone lesions or soft tissue plasmacyomas or definite increase in the size of existing bone lesions or soft tissue plasmacyomas, or development of hypercalcemia (corrected serum Ca++\>11.5 mg/dl) that can be attributed solely to plasma cell proliferative disease.

Percent of patients and the 95% Binomial Confidence interval who had any stage I-IV acute GvHD based on the modified Keystone Grading Scale for skin, liver and gastrointestinal symptoms for patients in Phase II. Zero means no acute GvHD was reported, and higher stages are worse outcomes (range of 0-4).

For skin: 0=no rash; 1=erthematous macular rash over \<25% body surface; 2=over 25-50% of body surface; 4=bullae, exfoliation ulcerative dermatitis.

For liver (bilirubin (mg/dL)): 0= \<2.0; 1= 2-\<2.9; 3= 3-\<5.9; 4= \>=15 . For gut changes (diarrhea\[ml/day\]): 0=none; 1= \>500-1000; 2= \>1000-1500; 3= \>1500; 4=severe abdominal pain with or without ileus.

Overall grade 0: Skin=0; liver=0; gut changes=0. Overall grade 1: Skin with 1 or 2; liver=0; gut changes=0. Overall grade 2: Skin with 1, 2, or 3; liver=1; gut changes=1. Overall grade 3: Skin with 2 or 3; liver with 2 or 3; gut changes with 2 or 3. Overall grade 4: Patients with grade 4 toxicity in any organ system.

Percent of patients and the 95% Binomial Confidence interval who had any chronic GvHD reported based on Filipovich et al. consensus document (BB\&MT 2005) and Akpek et al. chronic GvHD grading system (Blood 2003) for patients in Phase II.

Percent of patients and the 95% Binomial Confidence interval who had treatment-related deaths by 100 days for patients in Phase II.

Percent of patients and the 95% Binomial Confidence interval who had treatment-related deaths by 1 year for patients in Phase II.

Time to neutrophil engraftment will be analyzed by the Kaplan-Meier method. The time to engraftment of neutrophils is defined as the time from day 0 to the date of the first of three consecutive days after transplantation during which the absolute neutrophils count (ANC) is at least 0.5 x109/l. Patients surviving at least 14 days after transplant will be evaluable for this endpoint. Patients who did not have neutrophil engraftment before death will be censored at the date of death. The median and 95% confidence intervals will be provided.

Time to platelet engraftment will be analyzed by the Kaplan-Meier method. The time to engraftment of platelets is defined as the time from day 0 to the first of three consecutive Complete Blood Counts (CBCs) obtained on different days after transplantation during which the platelet count is at least 20 x109/l. The CBCs obtained should be at least seven days after the most recent platelet transfusion. Only patients who achieved engraftment of platelets will be included in the analysis. The median and 95% confidence intervals will be provided.

Celgene Corporation

Sherif S. Farag

Professor of Medicine

Standard treatment of sirolimus and tacrolimus as GvHD prophylaxis with sirolimus (target plasma drug level of 5-10 ng/ml) and lenalidomide (15 mg daily) as post-transplant maintenance

Phase I Dose Finding

Phase II

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Dr. Sherif Farag

All patients assigned to Phase I and received treatment medication.

Phase I: Number of Participants With Dose Limiting Toxicity

All patients who received treatment and were followed after transplant.

Phase II: Percent of Patients Alive and Free of Progression at 12 Months Following Transplant

All patients who received treatment and were followed after transplant

Phase II - Percent of Patients With Acute Graft Versus Host Disease (GvHD)

Phase II - Percent of Patients With Chronic Graft Versus Host Disease (GvHD)

Phase II - Percent of Patients With Treatment-related Deaths at 100 Days

Phase II - Percent of Patients With Treatment-related Deaths at 1 Year

All patients who received treatment and survived at least 14 days after transplant

Phase II - Time to Neutrophil Engraftment

All patients who received treatment and who achieved platelet recovery/engraftment of platelets

Spots Global Cancer Trial Database for Allo Transplant Followed by Lenalidomide and Sirolimus Maintenance in High-Risk Multiple Myeloma (MM)

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