Federal Register / Vol. 57, No. 166 / Wednesday, August 26, 1992 /. Nptices 
38735 
(CML). The retroviral vectors GlNa and 
LNL6 which code for neomycin 
resistance will be used to transduce 
autologous peripheral blood and bone 
marrow cells respectively; these are 
cells that have been removed and stored 
at the time of cytogenetic remission or 
re-induction of chronic phase in 
Philadelphia chromosome positive CML 
patients. Following reinduction of the 
chronic phase of CML and preparative 
chemotherapy, patients will be infused 
with the transduced autologous cells. 
"This protocol is designed to 
determine the source of relapse of CML. 
If polyclonal CML neomycin marked 
blastic cells appear at the time of 
relapse, their presence will indicate that 
relapse arises from the leukemic CML 
blast cells present in the autologous 
cells infused following chemotherapy. If 
residual systemic disease contributes to 
relapse, the neomycin resistance gene 
will not be detected in the CML 
leukemic blasts at the time of relapse. 
“By using two separate vectors 
detectable by the polymerase chain 
reaction assay (PCR), this study will 
compare the relative contributions of the 
peripheral blood and marrow to 
generate hematopoietic recovery after 
bone marrow transplantation and 
evaluate purging and selection of 
peripheral blood or bone marrow as a 
source of stem cells for transplant. The 
percentage of neomycin resistant CML 
cells which are leukemic will be 
determined by PCR analysis and 
detection of bcr-abl messenger RNA.” 
I accept this recommendation and 
Appendix D-XXX of the NIH Guidelines 
will be added accordingly, v- 
D. Addition of Appendix D-XXXI to the 
NIH Guidelines 
In a letter dated April 14, 1992, Dr. 
Cynthia Dunbar of the National 
Institutes of Health, Bethesda, 
Maryland, indicated her intention to 
submit three human gene transfer 
protocols to the RAC for formal review . 
and approval. The titles of these 
protocols are: “Genetic Marking with 
Retroviral Vectors to Study the Biology 
of Hematopoietic Reconstitution aft^r 
Autologous Transplantation for Multiple 
Myeloma,” "Genetic, Marking with 
Retroviral Vectors to Study the Biology 
of Hematopoietic Reconstitution after 
Autologous Transplantation for Breast 
Cancer,” and “Genetic Marking with 
Retroviral Vectors to Study the Biology 
of Hematopoietic Reconstitution after 
Autologous Transplantation for Chronic 
Myelogenous Leukemia.” This request 
was published for comment in the 
Federal Register of May 6, 992 (57 FR 
195121. 
These protocols were reviewed and 
recommended for approval during the 
RAC meeting on June 1-2, 1992. The 
RAC, by identical votes of 19 in favor, 0 
opposed, and no abstentions, approved 
the protocols. The following section may 
be added to Appendix D: 
Appendix D-XXXI 
“Dr. Cynthia Dunbar of the National 
Institutes of Health, Bethesda, 
Maryland, can conduct gene transfer 
experiments on up to 48 patients with 
multiple myeloma, breast cancer, or 
chronic myelogenous leukemia. The 
retroviral vectors GIN and LNL6 will be 
used to transfer the neomycin resistance 
marker gene into autologous bone 
marrow and peripheral blood stem cells 
in the presence of growth factors to 
examine hematopoietic reconstitution 
after bone marrow transplantation. The 
efficiency of transduction of both short 
and long term autologous bone marrow 
reconstituting cells will be examined. 
“Autologous bone marrow and 
CD34 + peripheral blood stem cells will 
be enriched prior to transduction. 
Myeloma and CML patients will receive 
both autologous bone marrow and 
peripheral blood stem cell 
transplantation. These separate 
populations will be marked with both 
the GlN and LNL8 retroviral vectors. If 
short and long term marking 
experiments are successful, important 
information may be obtained regarding 
the biology of autologous reconstitution, 
the feasibility of retroviral gene transfer 
into hematopoietic cells, and the 
contribution of viable tumor cells within 
the autograft to disease relapse.” 
I accept this recommendation and 
Appendix D-XXXI of the NIH 
Guidelines will be added accordingly. 
E. Addition of Appendix D-XXXII to the 
NIH Guidelines 
In a letter dated January 16, 1992, Dr. 
Bemd Gansbacher of the Memorial 
Sloan-Kettering Cancer Center, New 
York, New York, indicated his intention 
to submit a human gene therapy 
protocol to the RAC for formal review 
and approval. The title of the protocol is: 
"Immunization with HLA-A2 Matched 
Allogeneic Melanoma Cells that Secrete 
Interleukin-2 (IL— 2) in Patients with 
Metastatic Melanoma." This request 
was published for comment in the 
Federal Register of May 6. 1992 (57 FR 
19512). 
The protocol was reviewed and 
recommended for approval during the 
RAC meeting on June 1-2, 1992, with the 
following modifications: (1) the patient 
eligibility criteria will be defined as 
those who have a life expectancy of 
greater than four months and who have 
failed one course of conventional 
therapy, and (2) a revised statement will 
be included in the Informed Consent 
document regarding the description of 
research procedures. The RAC, by a 
vote of 20 in favor, 0 opposed, and no 
abstentions, approved the protocol. The 
following section may be added to 
Appendix D: 
Appendix D-XXXII 
“Dr. Bemd Gansbacher of the 
Memorial Sloan-Kettering Cancer 
Center, New York, New York, can 
conduct gene therapy experiments on 
twelve patients over 18 years of age 
with metastatic melanorma who are 
HLA-A2 positive and who have failed 
conventional therapy. This Phase I study 
will examine whether allogeneic HLA- 
A2 matched melanoma cells expressing 
recombinant human Interleukin-2 (IL-2) 
can be injected subcutaneously and 
used to create a potent tumor-specific 
immune response without producing 
toxicity. By allowing the tumor cells to 
present the MHC Class I molecule as 
well as the secreted IL-2, a clonal 
expansion of tumor-specific effector 
cells js expected. The effector 
populations may access residual tumor 
at distant sites via the systemic 
circulation." 
I accept this recommendation and 
Appendix D-XXXII of the NIH 
Guidelines will be added accordingly. 
F. Addition of Appendix D-XXXIII to 
the NIH Guidelines 
In a letter dated January 16, 1992, Dr. 
Bemd Gansbacher of the Memorial 
Sloan-Kettering Cancer Center, New 
York, New York, indicated his intention 
to submit a human gene therapy 
protocol to the RAC for formal review 
and approval. The title of this protocol 
is: "Immunization with IL-2 Secreting 
Allogeneic HLA-A2 Matched Renal Cell 
Carcinoma Cells in Patients with 
Advanced Renal Cell Carcinoma.” This 
request was published for comment in 
the Federal Register of May 6, 1992 (57 
FR 19512). 
The protocol was reviewed and 
recommended for approval during the 
RAC meeting on June 1-2, 1992, with a 
modification to the patient’s Informed 
Consent regarding the description of 
research procedures. The RAC, by a 
vote of 20 in favor, 0 opposed, and no 
abstentions, approved the protocol. The 
following section may be added to 
appendix D: 
Appendix D-XXXIII 
“Dr. Bemd Gansbacher of the 
Memorial Sloan-Kettering Cancer 
Center, New York. New York, can 
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