Allo Transplant Followed by Lenalidomide and Sirolimus Ma... | NCT01303965

NCT01303965

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Name	Class
Celgene Corporation	INDUSTRY

Description Module

Label	Type	Description	Intervention Names
Open Label, Single Arm	Experimental	Use sirolimus and tacrolimus as GvHD prophylaxis with sirolimus and lenalidomide as post-transplant maintenance	Drug: Sirolimus Drug: Tacrolimus Drug: Lenalidomide

Name	Type	Description	Arm Group Labels	Other Names
Sirolimus	Drug	Start on Day -3 and continue for 1 year	Open Label, Single Arm

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Phase I: Number of Participants With Dose Limiting Toxicity	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.	28 days
Phase II: Percent of Patients Alive and Free of Progression at 12 Months Following Transplant	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.	Transplant (Day 0) through 1 year post-transplant

Secondary Outcomes

Measure	Description	Time Frame
Phase II - Percent of Patients With Acute Graft Versus Host Disease (GvHD)	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.

Eligibility Module

Eligibility Criteria

Recipient Inclusion Criteria:

1. Understand and voluntarily sign an informed consent form.
2. Age 18-70 years at the time of signing the informed consent form.
3. Able to adhere to the study visit schedule and other protocol requirements.
4. Previously documented multiple myeloma (MM) with measurable monoclonal protein by either serum/urine protein electrophoresis or serum free light chains, or measurable plasmacytomas.
5. ECOG performance status of 0-2 at study entry (see Appendix 2).
6. Acceptable organ function as outlined in the protocol.
7. Otherwise fitting institutional criteria for allogeneic stem cell transplantation.
8. Presence of an HLA-matched (5/6 or 6/6 matched for HLA-A, B, and DR) sibling donor, or a HLA-matched (matched for at least HLA-A, B, C, and DRB1) unrelated donor by high-resolution testing.
9. Disease free of prior malignancies for >/= 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "insitu" of the cervix or breast.
10. All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.
11. Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test

Recipient Exclusion Criteria:

1. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
2. Pregnant or breast feeding females.
3. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
4. Known hypersensitivity to thalidomide or Lenalidomide.
5. The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
6. Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine or prior infection to which they are now immune (i.e., not carriers) are eligible.

Donor Inclusion Criteria:

The following categories of donor will be acceptable:

1. HLA-matched related donor (5/6 or 6/6 match): Minimal typing necessary is serologic typing for class I (A, B) and molecular typing for class II (DRB1).
2. HLA-matched Unrelated Donor (MUD): Molecular identity at least at HLA A, B, C, and DRB1 and DQB1 (8/10 match) by high resolution typing is required.
3. Syngeneic donors are not eligible.
4. The donor must be healthy and must be an acceptable donor as per institutional standards for marrow or stem cell donation.
5. Age ≥ 18 years

Name	Affiliation	Role
Sherif Farag, MD, PhD	IU Simon Cancer Center	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Indiana University Melvin and Bren Simon Cancer Center		Indianapolis	Indiana	46202	United States

ID	Title	Description
FG000	Phase I Dose Finding	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
FG001	Phase II	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

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Phase I Dose Finding	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
BG001	Phase II

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Phase I: Number of Participants With Dose Limiting Toxicity

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.

All patients assigned to Phase I and received treatment medication.

Posted

Count of Participants

Participants

28 days

ID	Title	Description
OG000	Phase I Dose Finding	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

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Phase I Dose Finding	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

ID	Term
D054219	Neoplasms, Plasma Cell
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D020141	Hemostatic Disorders

ID	Term
D018942	Macrolides
D007783	Lactones
D009930	Organic Chemicals
D010797	Phthalimides